Infectious Disease Project Pathogen-Based Infections

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WikiDoc Infectious Disease Project — Pathogen-Based Infections

Pathogens of Public Health Significance

3

Pathogens of Clinical Significance

3

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Bacteria – Gram-Positive Cocci

Enterococcus faecalis

Enterococcus faecalis Return to Top

1. Bacteremia^[1]

1.1 Ampicillin or penicillin susceptible

Preferred regimen (1): Ampicillin 2 g IV q4-6h
Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h

1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy

Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
Preferred regimen (2): Linezolid 600 mg IV q12h
Preferred regimen (3): Daptomycin 6 mg/kg IV q24h

1.3 Ampicillin and vancomycin resistant

Preferred regimen (1): Linezolid 600 mg IV q12h
Preferred regimen (2): Daptomycin 6 mg/kg IV q24h

2. Endocarditis^[2]^[3]

2.1 Endocarditis in adults

2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin

Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.

2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin

Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks

2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin

2.1.3.1 β Lactamase–producing strain

Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h 6 weeks
Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks

2.1.3.2 Intrinsic penicillin resistance

Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks

2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin

Preferred regimen (1): (Imipenem OR Cilastatin 2 g/day IV for ≥ 8weeks) AND Ampicillin 12 g/day IV for ≥ 8 weeks
Preferred regimen (2): Ceftriaxone sodium 4 g IV/IM q24h for ≥ 8weeks AND Ampicillin 12 g IV q24h for ≥ 8 weeks

2.2 Endocarditis in pediatrics

2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin

Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
Alternate regimen : Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks

2.2.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin

Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks

2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin

2.2.3.1 β Lactamase–producing strain

Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks

2.2.3.2 Intrinsic penicillin resistance

Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks

2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin

Preferred regimen: Imipenem/Cilastatin 60–100 mg/kg IV q24h for ≥ 8 weeks AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks
Alternate regimen: Ceftriaxone 100 mg/kg IV/IM q24h AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks

3. Meningitis^[4]

3.1 Ampicillin susceptible

Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h

3.2 Ampicillin resistant

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h

3.3 Ampicillin and vancomycin resistant

Preferred regimen: Linezolid 600 mg IV q12h

4. Urinary tract infections ^[5]

Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
Preferred regimen (2): Fosfomycin 3 g PO single dose
Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days

5. Intra abdominal or wound infections ^[6]

Preferred regimen (1): Penicillin
Preferred regimen (2): Ampicillin
Alternative regimen (Penicillin allergy or high-level Penicillin resistance): Vancomycin
Alternative regimen (For complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h

Enterococcus faecium Return to Top

1. Bacteremia^[7]

1.1 Ampicillin or penicillin susceptible

Preferred regimen (1): Ampicillin 2 g IV q4-6h
Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h

1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy

Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
Preferred regimen (2): Linezolid 600 mg IV q12h
Preferred regimen (3): Daptomycin 6 mg/kg IV q24h.

1.3 Ampicillin and vancomycin resistant

Preferred regimen (1): Linezolid 600 mg IV q12h
Preferred regimen (2): Daptomycin 6 mg/kg IV q24h

2. Endocarditis^[2]^[8]

2.1 Endocarditis in adults

2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin

Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks

Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.

2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin

Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks

2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin

2.1.3.1 β Lactamase–producing strain

Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks

2.1.3.2 Intrinsic penicillin resistance

Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks

2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin

Preferred regimen (1): Linezolid 1200 mg IV/PO q24h ≥ 8 weeks
Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks

2.2 Endocarditis in pediatrics

2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin

Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.

2.2.2 Strains Susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin

Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks

2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin

2.2.3.1 β Lactamase–producing strain

Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks

2.2.3.2 Intrinsic penicillin resistance
Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks

2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin

Preferred regimen (1): Linezolid 30 mg/kg IV/PO q24h ≥ 8 weeks
Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks

3. Meningitis^[4]

3.1 Ampicillin susceptible

Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h

3.2 Ampicillin resistant

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h

3.3 Ampicillin and vancomycin resistant

Preferred regimen: Linezolid 600 mg IV q12h

4. Urinary tract infections^[9]

Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
Preferred regimen (2): Fosfomycin 3 g PO single dose
Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days

5. Intra abdominal or wound infections ^[10]

Preferred regimen (1): Penicillin
Preferred regimen (2): Ampicillin
Alternative regimen (penicillin allergy or high-level penicillin resistance): Vancomycin
Alternative regimen (for complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h

Staphylococcus aureus Return to Top

Staphylococcus aureus treatment

1. Infectious endocarditis^[11]

1.1 In adults

Preferred regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
Preferred regimen (2): Daptomycin 6mg/kg/dose IV qd

2. Intravascular catheter-related infections^[12]

2.1 Methicillin susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q6h
Preferred regimen (2): Oxacillin 2 g IV q6h
Alternative regimen (1): Cefazolin 2 g IV q8h
Alternative regimen (2): Vancomycin 15 mg/kg IV q12h

2.1.1 Pediatric dose of Nafcillin

2.1.1.1 Neonates (< 4 weeks)

For < 1200 g: Nafcillin 50 mg/kg/day q12h
For ≤ 7 days of age and 1200–2000 g: Nafcillin 50 mg/kg/day q12h
For ≤ 7 days of age and > 2000 g: Nafcillin 75 mg/kg/day q8h
For > 7 days of age and 1200–2000 g: Nafcillin 75 mg/kg/day q8h
For > 7 days of age and > 2000 g: Nafcillin 100 mg/kg/day q6h

2.1.1.2 Infants and children (> 4 weeks)

Nafcillin 100–200 mg/kg/day q4–6h

2.1.2 Pediatric dose of Oxacillin

2.1.2.1 Neonates (< 4 weeks)

For < 1200 g: Oxacillin 50 mg/kg/day q12h
For Postnatal age < 7 days and 1200–2000 g: Oxacillin 50–100 mg/kg/day q12h
For Postnatal age < 7 days and > 2000 g: Oxacillin 75–150 mg/kg/day q8h
For Postnatal age ≥ 7 days and 1200–2000 g: Oxacillin 75–150 mg/kg/day q8h
For Postnatal age ≥ 7 days and > 2000 g: Oxacillin 100–200 mg/kg/day q6h

2.1.2.2 Infants and children(> 4weeks)

Oxacillin 150–200 mg/kg/day q4–6h

2.1.3 Pediatric dose of Cefazolin

2.1.3.1 Neonates (< 4 weeks)

Postnatal age ≤ 7 days: Cefazolin 40 mg/kg/day q12h
Postnatal age > 7 days and ≤ 2000 g: Cefazolin 40 mg/kg/day q12h

Postnatal age > 7 days and > 2000 g: Cefazolin 60 mg/kg/day q8h

2.1.3.2 Infants and children (> 4 weeks)

Cefazolin 50 mg/kg/day q8h.

2.1.4 Pediatric dose of Vancomycin

2.1.4.1 Neonates (< 4 weeks)

Postnatal age ≤ 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
Postnatal age ≤ 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q12–18h.
Postnatal age ≤ 7 days and > 2000 g: Vancomycin 10–15 mg/kg q8–12h.
Postnatal age > 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
Postnatal age > 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q8–12h.
Postnatal age > 7 days and > 2000 g: Vancomycin 15–20 mg/kg q8h.

2.1.4.2 Infants and children (> 4 weeks)

Vancomycin 40 mg/kg/day q6–8h.

2.2 Methicillin resistant Staphylococcus aureus (MRSA)

Preferred regimen (1): Vancomycin 15 mg/kg IV q12h
Preferred regimen (2): Daptomycin 6–8 mg/kg/day IV
Preferred regimen (3): Linezolid 10 mg/kg IV/PO q12h
Preferred regimen (4): Vancomycin 15 mg/kg IV q12h AND (Rifampicin IV or Gentamycin IV)
Preferred regimen (5): Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h alone (if susceptible)

2.2.1 Pediatric dose of Linezolid

2.2.1.1 Neonates (< 4 weeks)

For < 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
For < 7 days of age and ≥ 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
For ≥ 7 days and ≥ 1200 g: Linezolid 10 mg/kg q8h

2.2.1.2 Infants and children < 12 years (> 4 weeks)

Linezolid 10 mg/kg q8h

2.2.1.3 Children ≥ 12 years and adolescents

Linezolid 10 mg/kg q12h

2.2.2 Pediatric dose of Gentamycin

2.2.2.1 Neonates (< 4 weeks)

Premature neonates and < 1000 g: Gentamycin 3.5 mg/kg q24h
< 1200 g: Gentamycin 2.5 mg/kg q18-24h.
Postnatal age ≤ 7 days: Gentamycin 2.5 mg/kg q12h.
Postnatal age > 7 days and 1200–2000 g: Gentamycin 2.5 mg/kg q8-12h.
Postnatal age > 7 days and > 1200 g: Gentamycin 2.5 mg/kg q8h.
Premature neonates with normal renal function: Gentamycin 3.5–4 mg/kg q24h.
Term neonates with normal renal function: Gentamycin 3.5–5 mg/kg q24h.

2.2.2.2 Infants and children < 5 years (> 4 weeks)

Gentamycin 2.5 mg/kg q8h; qd dosing in patients with normal renal function, Gentamycin 5–7.5 mg/kg q24h.

2.2.2.3 Children ≥ 5 years

Gentamycin 2–2.5 mg/kg q8h; qd with normal renal function, Gentamycin 5–7.5 mg/kg q24h.

2.2.3 Pediatric dose of Trimethoprim-Sulfamethoxazole

2.2.3.1 Infants > 2 months of age and children of mild-to-moderate infections

Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h; serious infection- Trimethoprim-Sulfamethoxazole 15–20 mg TMP/kg/day q6-8h.

3. Cellulitis^[13]

3.1 Purulent cellulitis (defined as cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess)

3.1.1 In adults

Preferred regimen (1): Clindamycin 300–450 mg PO tid
Preferred regimen (2): Trimethoprim-Sulfamethoxazole 1–2 DS (double strength) tab PO bid
Preferred regimen (3): Doxycycline 100 mg PO bid
Preferred regimen (4): Minocycline 200 mg as a single dose THEN 100 mg PO bid
Preferred regimen (5): Linezolid 600 mg PO bid

3.1.2 In children

Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
Preferred regimen (3)

3.1 If patient body weight < 45kg then Doxycycline 2 mg/kg PO q12h
3.2 If patient body weight 45kg then Doxycycline adult dose

Preferred regimen (4): Minocycline 4 mg/kg PO 200 mg as a single dose, THEN Minocycline 2 mg/kg PO q12h
Preferred regimen (5): Linezolid 10 mg/kg PO q8h, (max: 600 mg)

3.2 Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)

3.2.1 In adults

Preferred regimen (1): Beta-lactam (eg, Cephalexin and Dicloxacillin) 500 mg PO qid
Preferred regimen (2): Clindamycin 300–450 mg PO tid
Preferred regimen (3): Amoxicillin 500 PO mg tid
Preferred regimen (4): Linezolid 600 mg PO bid
Note (1): Empirical therapy for beta-hemolytic streptococci is recommended. Empirical coverage for CA-MRSA is recommended in patients who do not respond to beta-lactam therapy and may be considered in those with systemic toxicity.
Note (2): Provide coverage for both beta-hemolytic streptococci and CA-MRSA beta-lactam (eg, Amoxicillin) with or without Trimethoprim-Sulfamethoxazole or a Tetracycline

3.2.2 In children

Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
Preferred regimen (3): Linezolid 10 mg/kg PO q8h, not to exceed 600 mg
Note (1): Clindamycin causes Clostridium difficile–associated disease may occur more frequently, compared with other oral agents.
Note (2): Trimethoprim-Sulfamethoxazole not recommended for women in the third trimester of pregnancy and for children ,2 months of age.
Note (3): Tetracyclines are not recommended for children under 8 years of age and are pregnancy category D.

4. Brain abscess^[14]^[15]^[16]

4.1 Methicillin-resistant Staphylococcus aureus (MRSA)

4.1.1 In adults

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks

4.1.2 In children

Preferred regimen (1): Vancomycin15 mg/kg/dose IV q6h
Preferred regimen (2): Linezolid 10 mg/kg/dose PO/IV q8h
Note: Consider the addition of Rifampin 600 mg qd OR 300–450 mg bid to Vancomycin.

4.2 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q4h
Preferred regimen (2): Oxacillin 2 g IV q4h
Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h

5. Cerebrospinal fluid shunt infection^[17]^[18]

5.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h with or without Rifampin 600 mg IV or PO q24h
Note: Shunt removal is recommended, and it should not be replaced until cerebrospinal fluid cultures are repeatedly negative.

5.2 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q4h with or without Rifampin 600 mg IV/PO q24h
Preferred regimen (2): Oxacillin 2 g IV q4h

6. Spinal epidural abscess^[19]^[20]^[21]^[22]

6.1 Penicillin-susceptible Staphylococcus aureus or Streptococcus

Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks

6.2 Methicillin-susceptible Staphylococcus aureus or Streptococcus

Preferred regimen (1): Cefazolin 2 g IV q8h for 2–4 weeks, THEN PO to complete 6–8 weeks
Preferred regimen (2): Nafcillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
Preferred regimen (3): Oxacillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, THEN PO to complete 6–8 weeks

6.3 Methicillin-resistant Staphylococcus aureus (MRSA)

6.3.1 In adults

Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV THEN Vancomycin 15–20 mg/kg IV q8–12h for 2–4 weeks, THEN PO to complete 6–8 weeks
Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks

6.3.2 Pediatric dose

Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.

7. Bacterial meningitis

7.1 Methicillin susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 9–12 g/day IV q4h
Preferred regimen (2): Oxacillin 9–12 g/day IV q4h
Alternative regimen (1): Vancomycin 30–45 mg/kg/day IV q8–12h
Alternative regimen (2): Meropenem 6 g/day IV q8h

7.2 Methicillin resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
Alternative regimen (1): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h
Alternative regimen (2): Linezolid 600 mg IV q12h
Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.

8. Septic thrombosis of cavernous or dural venous sinus^[23]

8.1 Methicillin-resistant Staphylococcus aureus (MRSA)

8.1.1 In adults

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 4–6 weeks
Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks

8.1.2 Pediatric dose

Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
Note (1): Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible.
Note (2): Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.

9. Subdural empyema

9.1 Methicillin-resistant Staphylococcus aureus (MRSA)^[24]

9.1.1 In adults

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks

9.1.2 In children

Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.

10. Acute conjunctivitis^[25]

10.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin ointment 1% qid

11. Appendicitis

11.1 Health care–associated complicated intra-abdominal infection^[26]

11.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h

12. Diverticulitis

12.1 Health care–associated complicated intra-abdominal infection^[26]

12.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h.

13. Peritonitis secondary to bowel perforation, peritonitis secondary to ruptured appendix, peritonitis secondary to ruptured appendix, typhlitis

13.1 Health care–associated complicated intra-abdominal infection^[26]

13.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h

14. Cystic fibrosis^[27]

14.1 Adults

14.1.1 If methicillin sensitive staphylococcus aureus

Preferred Regimen (1): Nafcillin 2 gm IV q4h
Preferred Regimen (2): Oxacillin 2 gm IV q4h

14.1.2 If methicillin resistant staphylococcus aureus

Preferred Regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
Preferred Regimen (2): Linezolid 600 mg PO/IV q12h

14.2 Pediatric

14.2.1 If methicillin sensitive staphylococcus aureus

Preferred Regimen (1): Nafcillin 5 mg/kg q6h (Age >28 days)
Preferred Regimen (2): Oxacillin 75 mg/kg q6h (Age >28 days)

14.2.2 If methicillin resistant staphylococcus aureus

Preferred Regimen (1): Vancomycin 40 mg/kg q6-8h (Age >28 days)
Preferred Regimen (2): Linezolid 10 mg/kg PO/IV q8h (up to age 12)

15. Bronchiectasis^[28]

15.1 In adults

15.1.1 Recommended first-line treatment and length of treatment

15.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Flucloxacillin 500 mg PO qds for 14 days

15.1.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Patient's body weight is < 50 kg

Preferred regimen: Rifampicin 450 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days

Patient's body weight is > 50 kg

Preferred regimen: Rifampicin 600 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days

15.1.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen (1): Vancomycin 1 g IV bd (monitor serum levels and adjust dose accordingly)
Preferred regimen (2): Teicoplanin 400 mg qd for 14 days

15.1.2 Recommended second-line treatment and length of treatment

15.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Clarithromycin 500 mg PO bd 14 days

15.1.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Patient's body weight is < 50 kg

Preferred regimen: Rifampicin 450 mg PO qd AND Doxycycline 200 mg PO qd for 14 days

Patient's body weight is > 50 kg

Preferred regimen: Rifampicin 600 mg PO qd AND Doxycycline 200 mg PO qd for 14 days

Third-line: Linezolid 600 mg bd for 14 days

15.1.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Linezolid 600 mg IV bd for 14 days

15.2 In children

15.2.1 Recommended first-line treatment and length of treatment

15.2.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Flucloxacillin

15.2.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)

15.2.1.2.1 Children (< 12 yr)

Preferred regimen: Trimethoprim 4-6 mg/kg/day PO q12h

15.2.1.2.2 Children (> 12 yr)

Preferred regimen (1): Trimethoprim 100-200 mg PO q12h
Preferred regimen (2): Rifampicin 450 mg PO od (or Rifampicin 600 mg PO od)

15.2.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen (1): Vancomycin 45-60 mg/kg/day IV q8-12h
Preferred regimen (2): Teicoplanin 400 mg qd for 14 days

15.2.2 Recommended second-line treatment and length of treatment

15.2.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Clarithromycin 15 mg/kg/day PO q12h

15.2.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen (1): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
Preferred regimen (2): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
Third-line: Linezolid 10 mg/kg PO/IV q12h

15.2.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Linezolid 10 mg/kg PO/IV q12h

15.3 Long-term oral antibiotic treatment

15.3.1 In adults

15.3.1.1 Recommended first-line treatment and length of treatment

15.3.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Flucloxacillin 500 mg PO bd

15.3.1.2 Recommended second-line treatment and length of treatment

15.3.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen: Clarithromycin 250 mg PO bd

16. Empyema^[29]

Preferred regimen (1): Nafcillin 2 gm IV q4h
Preferred regimen (2): oxacillin 2 gm IV q4h (if MSSA)
Alternative regimen (1): Vancomycin 1 gm IV q12h
Alternative regimen (2): Linezolid 600 mg PO bid (if MRSA)

17. Community-acquired pneumonia^[30]

17.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred Regimen (1): Nafcillin 1000-2000 mg q4h
Preferred Regimen (2): Oxacillin 2 g IV q4h
Preferred Regimen (3): Flucloxacillin 250 mg IM/IV q6h
Alternative Regimen (1): Cefazolin 500 mg IV q12h
Alternative Regimen (2): Clindamycin 150-450 mg PO q6-8h

17.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred Regimen (1): Vancomycin 45-60 mg/kg/day q8-12h (max: 2000 mg/dose) for 7-21 days
Preferred Regimen (2): Linezolid 600 mg PO/IV q12h for 10-14 days
Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

18. Olecranon bursitis or prepatellar bursitis

18.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q4h
Preferred regimen (2): Oxacillin 2 g IV q4h
Preferred regimen (3): Dicloxacillin 500 mg PO qid

18.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen (1): Vancomycin 1 g IV q12h
Preferred regimen (2): Linezolid 600 mg PO qd
Note: Initially aspirate q24h and treat for a minimum of 2–3 weeks.

19. Septic arthritis

19.1 In adults

19.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
Alternative regimen (2): Linezolid 600 mg PO/IV q12h
Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h

19.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q6h
Preferred regimen (2): Clindamycin 900 mg IV q8h
Alternative regimen (1): Cefazolin 0.25–1 g IV/IM q6–8h
Alternative regimen (2): Vancomycin 500 mg IV q6h or 1 g IV q12h

19.2 In childern

Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
Preferred regimen (2): Daptomycin 6–10 mg/kg IV q24h
Preferred regimen (3): Linezolid 10 mg/kg PO/IV q8h
Preferred regimen (4): Clindamycin 10–13 mg/kg PO/IV q6–8h

20. Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)

20.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin 2 g IV q4–6h
Preferred regimen (2): Oxacillin 2 g IV q4–6h
Alternative regimen (1): Cefazolin 1–2 g IV q8h
Alternative regimen (2): Ceftriaxone 2 g IV q24h
Alternative regimen (if allergic to penicillins) (3): Clindamycin 900 mg IV q8h
Alternative regimen (if allergic to penicillins) (4): Vancomycin 15–20 mg/kg IV q8–12h, (max: 2 g per dose)

20.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Early-onset (2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)
Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
Alternative regimen (1): Daptomycin 6 mg/kg IV q24h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
Alternative regimen (2): Linezolid 600 IV q8h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
Note: The above regimen should be followed by Rifampin and a Fluoroquinolone, TMP/SMX, a Tetracycline or Clindamycin for 3-6 months for hips and knees, respectively.

21. Hematogenous osteomyelitis

21.1 Adult (> 21 yrs)

21.1.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible

Preferred regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)

21.1.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely

Preferred regimen (1): Nafcillin
Preferred regimen (2): Oxacillin 2 gm IV q4h

21.2 Children (> 4 months)-Adult

21.2.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible

Preferred regimen: Vancomycin 40 mg IV q6–8h

21.2.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely

Preferred regimen (1): Nafcillin
Preferred regimen (2): Oxacillin q6h (max. 8–12 gm per day)
Note: Add Ceftazidime 50 mg q8h or Cefepime 150 mg q8h if Gram negative bacilli on Gram stain

21.3 Newborn (< 4 months.)

21.3.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible

Preferred regimen (1): Vancomycin AND Ceftazidime 2 gm IV q8h
Preferred regimen (2): Vancomycin AND Cefepime 2 gm IV q12h

21.3.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely

Preferred regimen (1): Nafcillin AND Ceftazidime
Preferred regimen (2): Oxacillin AND Cefepime

21.4 Specific therapy

21.4.1 Methicillin-susceptible Staphylococcus aureus (MSSA)

Preferred regimen (1): Nafcillin
Preferred regimen (2): Oxacillin 2 gm IV q4h
Preferred regimen (3): Cefazolin 2 gm IV q8h
Alternative regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)

21.4.2 Methicillin-resistant Staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin 1 gm IV q12h
Alternative regimen: Linezolid 600 mg q12h PO/IV with or without Rifampin 300 mg PO/IV bid

22. Diabetic foot osteomyelitis

High risk for MRSA

Preferred regimen (1): Linezolid 600 mg IV or PO q12h
Preferred regimen (2): Daptomycin 4 mg/kg IV q24h
Preferred regimen (3): Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)

23. Necrotizing fasciitis^[31]

23.1 In adult

Preferred regimen (1): Nafcillin 1–2 g IV q4h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
Preferred regimen (2): Oxacillin 1–2 g IV q4h
Preferred regimen (3): Cefazolin 1 g IV q8h
Preferred regimen (4): Vancomycin 15 mg/kg IV bid
Preferred regimen (5): Clindamycin 600–900 mg IV q8h

23.2 In childern

Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (Bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin resistent staphylococcus aureus)

24. Staphylococcal toxic shock syndrome^[32]

24.1 Methicillin sensitive Staphylococcus aureus

Preferred regimen (1): Cloxacillin 250-500 mg PO q6h (max dose: 4 g/24 hr)
Preferred regimen (2): Nafcillin 4-12 g/24 hr IV q4-6hr (max dose: 12 g/24 hr)
Preferred regimen (3): Cefazolin 0.5-2g IV/IM q8h (max dose: 12 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
Alternative regimen (1): Clarithromycin 250-500 mg PO q12h (max dose: 1 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO)
Alternative regimen (2): Rifampicin AND Linezolid 600 mg IV/PO q12h
Alternative regimen (3): Daptomycin
Alternative regimen (4): Tigecycline 100 mg loading dose THEN 50 mg IV q12h

24.2 Methicillin resistant Staphylococcus aureus

Preferred regimen (1): Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24h IV/IM or 2 g/24h PO)
Preferred regimen (2): Linezolid 600 mg IV/PO q12h AND Vancomycin 15-20 mg/kg IV q8-12h, (max: 2 g per dose)
Preferred regimen (3): Teicoplanin
Alternative regimen (1): Rifampicin AND Linezolid 600 mg IV/PO q12h
Alternative regimen (2): Daptomycin
Alternative regimen (3): Tigecycline 100 mg loading dose THEN 50 mg IV q12h

24.3 Glycopeptide resistant or intermediate Staphylococcus aureus

Preferred regimen: Linezolid 600 mg IV/PO q12h AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO) (if sensitive)
Alternative regimen (1): Daptomycin
Alternative regimen (2): Tigecycline 100 mg loading dose THEN 50 mg IV q12h

Staphylococcus aureus ,prophylaxis

1. Prophylaxis for coronary artery bypass graft-associated acute mediastinitis^[33]

1.1 Methicillin susceptible staphylococcus aureus (MSSA)

Preferred regimen: A first- or second-generation Cephalosporin is recommended for prophylaxis in patients without MRSA colonization.

1.2 Methicillin resistant staphylococcus aureus (MRSA)

Preferred regimen: Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recommended for prophylaxis in patients with proven or suspected MRSA colonization
Note (1): Preoperative antibiotics should be administered to all patients to reduce the risk of mediastinitis in cardiac surgery.
Note (2): The use of intranasal Mupirocin is reasonable in nasal carriers of Staphylococcus aureus.

Staphylococcus haemolyticus Return to Top

1. Methicillin-susceptible strain^[34]^[35]

Preferred regimen (1): Nafcillin 1–2 g IV q4-6h (maximum 12 g/day)
Preferred regimen (2): Oxacillin 1–2 g IVq4-6h (maximum 12 g/day)
Preferred regimen (3): Cefazolin 0.5–2 g IV q6-8h
Alternative regimen (1): TMP-SMX 4–5 mg/kg IV q6–12h
Alternative regimen (2): Doxycycline 100–200 mg IV q12-24h

2. Methicillin-resistant, Glycopeptide-susceptible strain

Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h

3. Methicillin-resistant, Glycopeptide-resistant strain

Preferred regimen (1): Daptomycin 4–6 mg/kg IV q24h
Preferred regimen (2): Linezolid 600 mg PO/IV q12h

Staphylococcus epidermidis Return to Top
Staphylococcus epidermidis^[36]

1. Methicillin-sensitive Staphylococcus epidermidis

Preferred regimen (1): Oxacillin 1-2 g IV q4h
Preferred regimen (2): Nafcillin 1-2 g IV q4h
Preferred regimen (3): Cephalothin
Alternative regimen: Rifampin 600 mg/day PO qd PLUS Sulfamethoxazole and Trimethoprim OR Fluoroquinolones AND Daptomycin 600 mg PO/IV q12h^[37]
Note: 75% of the S. epidermidis are methicillin-resistant.

2. Methicillin-resistant Staphylococcus epidermidis

Preferred regimen: Vancomycin 1 g IV q12h ± Rifampin 600 mg/day PO qd

Note: For deep-seated infections consider adding Gentamicin AND/OR Rifampin 600 mg/day PO qd to the regimen^[11]
3. Prosthetic device infections

Preferred regimen: Oxacillin 1-2 g IV q4h OR Vancomycin 1 g IV q12h PLUS Rifampin 600 mg/day PO qd AND Gentamicin 3 mg/kg/day IV/IM q8-24h is appropriate^[11]

Note: Duration depends on site of infection and severity.

Staphylococcus lugdunensis Return to Top

Staphylococcus lugdunensis treatment

1. Skin and soft tissue infections^[38]

Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks

Note: Abscesses should be drained if possible.

2. Endocarditis^[39]

2.1 Native valve infectious endocarditis

Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)

Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).

2.2 Prosthetic valve infective endocarditis

Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks

Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system

3. Bacteremia^[12]

Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks

Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable

2.1 The patient is not diabetic or immunosuppressed.
2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.

4. Prosthetic devices^[40],^[12]

Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
Preferred regimen (4): Linezolid 600 mg IV q12h

5. Vertebral osteomyelitis, discitis

Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose

6. Septic arthritis in adults

Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks

Staphylococcus saprophyticus Return to Top

1. Urinary tract infections^[41]

Preferred regimen (1): Cephalexin 500 mg PO qid
Preferred regimen (2): Amoxicillin-Clavulanate 875/125 mg PO bid
Preferred regimen (3): TMP-SMX 160–800 mg PO bid
Alternative regimen: Levofloxacin 500 mg PO qd

Streptobacillus moniliformis Return to Top

Streptococcus moniliformis treatment^[42]

1. Migratory arthropathy and arthritis

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

2. Diarrhea, (especially kids) liver or spleen abscess

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

3. Undifferentiated fever

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

4. Endocarditis, myocarditis, pericarditis (cardiac)

Preferred regimen: Penicillin 20 MU/day IV divided q4h. Optimal duration recommendation for infective endocarditis is 4 weeks.
Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.

5. Meningitis, brain abscess

Preferred regimen: Penicillin 20 MU/day IV divided q4h.
Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.

6. Anemia

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

7. Pneumonia

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

8. Amnionitis (pregnancy)

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

9. Renal abscess

Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.

Streptococcus anginosus Return to Top

1. Dental abscess^[43]

Preferred regimen: Penicillin V 500 mg PO qid
Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h

2. Brain abscess

Preferred regimen (1): Penicillin G 18–24 MU/day IV q4–6h
Preferred regimen (2): Ceftriaxone 2 g IV q12h
Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h

Streptococcus pneumoniae Return to Top

Streptococcus pneumonia treatment

1. Lung (Community-acquired pneumonia)^[30]

1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mcg/ml)

Preferred regimen: Penicillin G 5 to 24 MU IV in equally divided doses q4-6h, Amoxicillin 1 g PO tid (+/- macrolide)
Alternative regimen: Macrolides (Azithromycin (IV) 500 mg IV qd for at least 2 days followed by 500 mg PO qd 7 to 10 days or Clarithromycin extended-release tablets 1000 mg PO qd for 7 days) and Oral Cephalosporins-Cefpodoxime 200 mg PO bd, (Cefprozil 500 mg PO bd, Cefditoren 400 mg PO bd, Cefdinir 300 mg PO bd), OR parenteral Cephalosporins-Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), Clindamycin 600 to 1200 mg IV or IM q6-12h, do not give single IM doses >600 mg; IV infusion rates should not exceed 30 mg/min , Doxycycline 100 mg PO bd, respiratory flouroquniolones.

1.2 Penicillin-resistant (Penicillin minimum inhibitory concentration ≥2)

Preferred regimen: Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), respiratory Flouroquniolones Levofloxacin (Levaquin) 500 mg IV/PO q24h for 7 to 14 days or 750 mg IV/PO q24h for 5 days (or Moxifloxacin (Avelox) 400 mg PO/IV over 60 minutes q24h for 7 to 14 days)
Alternative regimen: Vancomycin 2 g/day IV q6-12h over at least 60 minutes, Linezolid 600 mg IV/PO q12h for 7 to 21 days , high-dose Amoxicillin (3 g qd with Penicillin minimum concentration of inhibitory <4 mcg/mL).

2.Endocarditis^[11]

Preferred regimen (1): Aqueous crystalline Penicillin-G 6 MU q4-6h IV for 4 weeks
Preferred regimen (2) (who are unable to tolerate beta lactams therapy): Vancomycin 15 mg/kg IV every 12 hours (target trough concentration, 10 to 15 mcg/mL) [9]; for troughs of 15 to 20 mcg/mL (MIC, 1 mcg/mL or less), dose 15 to 20 mg/kg (actual body weight) IV every 8 to 12 hours for most patients with normal renal function
Preferred regimen (3) (If the isolate is resistant (MIC 2 g/mL) to cefotaxime): Cefotaxime 1-2 g q8-12h IV or IM (max dose: 12 g/24 hr) AND Vancomycin 15 mg/kg/day IV q12h AND Rifampin 300 mg IV/PO q8h for 6 weeks, in combination with appropriate antimicrobial therapy
Alternative regimen (1): Cefazolin 0.5-2 g q8h IV or IM (max dose: 12 g/24 hr)
Alternative regimen (2): Ceftriaxone 2 g IV q12h

Note : Streptococcus pneumoniae with intermediate doses minimum inhibitory concentration (MIC) 0.12 g/mL–0.5 g/mL Penicillin resistance (MIC 0.1 to 1.0 g/mL) or high Penicillin resistance (MIC 2.0 g/mL) is being recovered from patients with bacteremia.

3. Sinuses (sinusitis)^[44]

Empiric therapy

3.1 For initial empiric treatment of acute bacterial rhinosinusitis in adults

Preferred regimen: Amoxicillin 500 mg/Clavulanate 125 mg PO tid or Amoxicillin 875 mg/Clavulanate 125 mg PO bid for 5 to 7 days recommended by the Infectious Disease Society of America (IDSA)
Alternative regimen (1): Doxycycline 100 mg PO q12h

Note: Doxycycline can be used in patients with Penicillin allergy.

Alternative regimen (2): A respiratory Fluoroquinolone (Levofloxacin or Moxifloxacin) is another recommended drug for Penicillin-allergic patients.

3.2 For second-line high-dose therapy for acute bacterial rhinosinusitis in adults

Preferred regimen: Amoxicillin 2 g/Clavulanate 125 mg PO bid recommended by the Infectious Disease Society of America (IDSA).
Note: The second line high dose therapy is recommended in adults who have failed initial therapy, in regions of high endemic rates (10% or greater) of invasive Penicillin-nonsusceptible Streptococcus pneumoniae, severe infection.

4. Bronchi (acute exacerbation of chronic bronchitis)^[45]

Preferred regimen (1): Amoxicillin 875 mg PO q12h or 500 mg PO q8h
Preferred regimen (2): Doxycycline 100 mg PO q12h

5. CNS (meningitis)^[4]

Empiric therapy

Preferred regimen: Vancomycin 15 mg/kg/day IV q12h AND a third-generation cephalosporin (Ceftriaxone 2 g IV q12h OR Cefotaxime 2 g IV q4h or 3 g q6h) AND Rifampin 600 mg IV qd in combination with Vancomycin
Alternative regimen: Meropenem, fluoroquinolones

Note: Middle ear infections (otitis media), peritoneum infections (spontaneous bacterial peritonitis), pericardium infections (purulent pericarditis), skin infections (cellulitis) and eye infections (conjunctivitis) caused by Streptococcus pneumonia.

Prevention

1. Pneumovax (23-valent) prevents bacteremia; impact on rates of CAP are modest or nil.
2. Prevnar vaccine for children <2 yrs age prevents invasive pneumococcal infection in adults by herd effect. Impact is impressive with rates of invasive pneumococcal infection down 80% in peds and 20-40% in adults.
3. Risk for bacteremia in splenectomy, HIV, smokers, black race, multiple myeloma, asthma.

Streptococcus pyogenes Return to Top
1. Streptococcus pyogenes tonsilitis^[46]

Preferred regimen (1): Penicillin V 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days^[47]
Preferred regimen (2): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose^[48]
Alternative regimen (1): Amoxicillin 50 mg/kg/day PO qd for 10 days OR 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract^[49]
Alternative regimen (2): first generation Cephalosporins are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy^[50]^[48]
Alternative regimen (3): Clarithromycin 250 mg PO bid for 10 days OR Azithromycin 12 mg/kg maximum 500 mg PO on day 1 THEN 6 mg/kg maximum 250 mg PO qd on days 2 through 5 OR Erythromycin 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
Alternative regimen (4): Clindamycin for penicillin-intolerant patients with erythromycin-resistant strains.
Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies^[51]

2. Recurrent Streptococcus pyogenes tonsilitis^[52]

Preferred regimen (1): Clindamycin 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
Preferred regimen (2): Amoxicillin-clavulanic acid 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
Alternative regimen: Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose ± Rifampin 20 mg/kg/day PO bid for 4 days

3. Secondary prophylaxis for rheumatic fever^[48]

Preferred regimen (1): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM every 4 weeks
Alternative regimen (1): Penicillin V potassium 250 mg PO bid
Alternative regimen (2): Sulfadiazine if <27kg 0.5 g PO qd, if >27kg 1 g PO qd
Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic

4. Streptococcus pyogenes bacteremia^[53]

Preferred regimen: Penicillin G 4 million units IV q4h AND Clindamycin 900 mg IV q8h for at least 14 days
Penicillin is added to the regimen to cover any other group A streptococcus which might be resistant to Clindamycin.
Alternative regimen (1): Erythromycin
Alternative regimen (2): Azithromycin
Alternative regimen (3): Clarithromycin
Alternative regimen (4): any other β-lactam^[54]
Note (1): Macrolide resistance is increasing.
Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
Note (3): If shock, administer massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.

5. Streptococcus pyogenes celulitis

Preferred regimen: treat as Streptococcus pyogenes bacteremia

6 Epiglottitis in childern^[55]

Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h
Alternative regimen (1): Amoxicillin-SB 100–200 mg/kg qd q6h
Alternative regimen (2): Trimethoprim-Sulfamethoxazole 8–12 mg/kg bid
Note: Have tracheostomy set “at bedside.” Chloro is effective, but potentially less toxic alternative agents available.

7 Burn wound sepsis^[56]

Preferred regimen: Vancomycin 1 gm IV q12h AND (Amikacin 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) AND [ Piperacillin 4 g IV q4h (give ½ q24h dose of Piperacillin into subeschar tissues with surgical eschar removal within 12 hours]. Can use Piperacillin-Tazobactam if Piperacillin not available.

8. Soft tissue^[57]

Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.

9. Muscle^[58]

Note: For myositis-debirdement is recommended.

10. Eye^[59]

10.1 Keratitis

10.1.1 Acute bacterial keratitis

Preferred regimen: Moxifloxacin eye gtts. 1 gtt tid for 7 days
Alternative therapy: Gatifloxacin eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
Note: Prefer Moxifloxacin due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).

10.1.2 Keratitis due to dry cornea, diabetes, immunosuppression

Preferred regimen: Cefazolin (50 mg/mL) AND (Gentamicin OR Tobramycin (14 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction)
Alternative therapy: Vancomycin (50 mg/mL) AND Ceftazidime (50 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction.
Note: Specific therapy guided by results of alginate swab culture and sensitivity. Ciprofloxacin 0.3% found clinically equivalent to CefazolinAND Tobramycin; only concern was efficacy of Ciprofloxacin vs S. pneumoniae

10.2 Dacryocystitis (lacrimal sac)

Preferred regimen: Moxifloxacin 1 gtt tid for 7 days OR Cefazolin (50 mg/mL) (1 gtt = 1 drop)

11. Suppurative phlebitis^[60]

Preferred regimen: Vancomycin 15 mg/kg IV q12h (normal weight)
Alternative regimen: Daptomycin 6 mg/kg IV q12h
Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.

12. Infected prosthetic joint^[61]

Preferred regimen: Penicillin G 2 million units IV q4h OR Ceftriaxone 2 g IV q24h for 4 weeks
Note: Debridement & prosthesis retention with intravenous antibiotics.

13. “Hot” tender parotid swelling^[62]

Preferred regimen: Nafcillin OR Oxacillin 2 g IV q4h
Note: Predisposing factors are stone(s) in Stensen’s duct, dehydration. Therapy depends on ID of specific etiologic organism.

14. Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)^[63]

Preferred regimen: (Trimethoprim-Sulfamethoxazole 800/160 mg 1-2 tabs PO bid OR Minocycline 100 mg PO bid) AND (Penicillin VK 500 mg PO qid OR selected Cephalosporins 2nd, 3rd generation - cefprozil 500 mg PO bid OR cefuroxime axetil 500 mg PO bid OR cefdinir 300 mg PO bid or 600 mg PO qd OR cefpodoxime 200 mg PO bid OR Fluoroquinolones Levofloxacin 750 mg PO qd).

15. Recurrent cellulitis, chronic lymphedema prophylaxis^[64]

Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxazole 800/160 mg 1 tablet PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.

Streptococcus agalactiae Return to Top

Streptococcus agalactiae treatment (GBS-group B Streptococcus)

1. Early onset group B streptococcal infections^[65]

1.1 Bacteremia or sepsis or pneumonia

1.1.1 Empiric therapy

Preferred regimen: Ampicillin 150 mg/kg IV q12h for 10 days AND Gentamicin 4 mg/kg IV q12h for 10 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 10 days-for infants born at < 35 weeks gestation

1.1.2 Definitive therapy

Preferred regimen: Penicillin G 50,000-100,000 units/kg per day IV divided q12h for 10 days

1.2 Meningitis

1.2.1 Empiric therapy

Preferred regimen: Ampicillin 100-150 mg/kg IV q8h for 14-21 days AND Gentamicin 4 mg/kg IV q24h for 14-21 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 14-21 days-for infants born at < 35 weeks gestation

1.2.2 Definitive therapy

Preferred regimen: Penicillin G 250,000-450,000 units/kg per day IV divided q8h for 14-21 days
Note: Cellulitis is the most frequent clinical manifestation of GBS-associated skin and soft tissue infections.

2. Late onset group b streptococcus infections in neonates and young infants (age > 1 week and body weight ≥ 1 kg with normal renal function)^[66]

2.1 Bacteremia without a focus

2.1.1 Empiric therapy

Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)

2.1.2 Definitive therapy

Preferred regimen: Penicillin G 75,000-150,000 units/kg per day IV divided q8h for 10 days

2.2 Meningitis

2.2.1 Empiric therapy

Preferred regimen: Ampicillin IV for 14-21 days with or without Vancomycin IV for 14-21 day AND Gentamicin IV for 14-21 days OR Cefotaxime IV for 14-21 day

2.2.2 Definitive therapy

Preferred regimen: Penicillin G 450,000-500,000 units/kg per day IV divided q6h for 14-21 days

2.3 Cellulitis or adenitis

2.3.1 Empiric therapy

Preferred regimen: Nafcillin IV for 10-14 days (OR [[Vancomycin IV for 10-14 days) AND Gentamicin IV for 10-14 days (OR Cefotaxime IV for 10-14 days)

2.3.2 Definitive therapy

Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10-14 days

2.4 Septic arthritis

2.4.1 Empiric therapy

Preferred regimen: Nafcillin IV for 14-21 days OR Vancomycin IV for 14-21 days AND Cefotaxime IV for 14-21 days

2.4.2 Definitive therapy

Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 14-21 days

2.5 Osteomyelitis

2.5.1 Empiric therapy

Preferred regimen: Nafcillin IV for 21-28 days OR Vancomycin IV for 21-28 days AND Cefotaxime IV for 21-28 days

2.5.2 Definitive therapy

Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 21-28 days

2.6 Urinary tract infection

2.6.1 Empiric therapy

Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)

2.6.2 Definitive therapy

Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10 days

Neonatal prophylaxis^[67]

Group B streptococcus infection (maternal dose for neonatal prophylaxis)

Preferred regimen: Penicillin-G, Ampicillin 2 g IV initial dose, THEN 1 g q4h until delivery, Cefazolin ≥ 4h prior to delivery

Bacteria – Gram-Positive Bacilli

Actinomycosis Return to Top
Actinomyces species including A. israeli^[68]

Preferred regimen: Penicillin 3-4 million units IV q4h for 2-6 weeks THEN Penicillin V 2-4 g/day PO qid for 6-12 months
Alternative regimen (1): Erythromycin 500-1000 mg IV q6h OR 500 mg PO qid
Alternative regimen (2): Tetracyclin 500 mg PO qid
Alternative regimen (3): Doxycycline 100 mg IV q12h OR 100 mg PO bid
Alternative regimen (4): Clindamycin 900 mg IV q8h OR 300-450 mg PO qd
Alternative regimen (5): Minocycline 100 mg IV q12h OR 100 mg PO bid

Arcanobacterium haemolyticum Return to Top

Arcanobacterium haemolyticum treatment

Preferred regimen: Erythromycin Base: 333 mg PO q8h; estolate/stearate/base: 250-500 mg q6h PO
Alternative regimen: Benzathine Penicillin G 1.2 MU IM q3-4 weeks

Note: Arcanobacterium haemolyticum is sensitivity to most drugs but resistent to Trimethoprim-Sulfamethoxazole

Anthracis

Bacillus anthracis Return to Top

Bacillus anthracis treatment

1. Treatment for cutaneous anthrax, without systemic involvement^[69]

Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (1): Ciprofloxacin 500 mg PO bid for 7-10 days

Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (2): Doxycycline 100 mg PO bid for 7-10 days

Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (3): Levofloxacin 750 mg PO qd for 7-10 days

Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (4): Moxifloxacin 400 mg PO qd for 7-10 days

Alternative regimen (1): Clindamycin 600 mg PO tid for 7-10 days

Alternative regimen (2): Amoxicillin 1 g PO tid (for penicillin-susceptible strains) for 7-10 days

Alternative regimen (3): Penicillin VK 500 mg PO qid (for penicillin-susceptible strains) for 7-10 days

Note: Duration of treatment is 60 days for bioterrorism-related cases and 7-10 days for naturally acquired cases.

2. Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck^[69]

2.1 Systemic anthrax with possible/confirmed meningitis

2.1.1 Bactericidal agent (fluoroquinolone)

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2-3 weeks

Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2-3 weeks

Preferred regimen (3): Moxifloxacin 400 mg IV q24h for 2-3 weeks AND

2.1.2 Bactericidal agent (ß-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen (1): Meropenem 2 g IV q8h for 2-3 weeks

Preferred regimen (2): Imipenem 1 g IV q6h for 2-3 weeks

Preferred regimen (3): Doripenem 500 mg IV q8h for 2-3 weeks

Preferred regimen (4): Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) for 2-3 weeks

Preferred regimen (5): Ampicillin 3 g IV q6h (for penicillin-susceptible strains) for 2-3 weeks AND

2.1.3 Protein synthesis inhibitor

Preferred regimen (1): Linezolid 600 mg IV q12h for 2-3 weeks

Preferred regimen (2): Clindamycin 900 mg IV q8h for 2-3 weeks

Preferred regimen (3): Rifampin 600 mg IV q12h for 2-3 weeks

Preferred regimen (4): Chloramphenicol 1 g IV q6-8h for 2-3 weeks

Note (1): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.

Note (2): Increased risk for seizures associated with Imipenem/Cilastatin treatment.

Note (3): Linezolid should be used with caution in patients with thrombocytopenia because it might exacerbate it. Linezolid use for > 14 days has additional hematopoietic toxicity.

Note (4): Rifampin is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.

2.2 Systemic anthrax when meningitis has been excluded

2.2.1 Bactericidal agent

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks

Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks

Preferred regimen (3): Moxifloxacin 400 mg q24h for 2 weeks

Preferred regimen (4): Meropenem 2 g IV q8h for 2 weeks

Preferred regimen (5): Imipenem 1 g IV q6h for 2 weeks

Preferred regimen (6): Doripenem 500 mg IV q8h for 2 weeks

Preferred regimen (7): Vancomycin 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) for 2 weeks

Preferred regimen (8): Penicillin G 4 MU IV q4h (penicillin-susceptible strains) for 2 weeks

Preferred regimen (9): Ampicillin 3 g IV q6h (penicillin-susceptible strains) for 2 weeks AND

2.2.2 Protein synthesis inhibitor

Preferred regimen (1): Clindamycin 900 mg IV q8h for 2 weeks

Preferred regimen (2): Linezolid 600 mg IV q12h for 2 weeks

Preferred regimen (3): Doxycycline 200 mg IV initially, then 100 mg IV q12h for 2 weeks

Preferred regimen (4): Rifampin 600 mg IV q12h for 2 weeks

Note: Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.

3. Specific considerations

3.1 Treatment of anthrax for pregnant Women

3.1.1 Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis ^[70]

3.1.1.1 A Bactericidal Agent (Fluoroquinolone)

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2–3 weeks OR

Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2–3 weeksOR

3.1.1.2 A Bactericidal Agent (ß-lactam)

3.1.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen: Meropenem 2 g q8h for 2–3 weeks

3.1.1.2.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1): Ampicillin 3 g IV q6h for 2–3 weeks

Alternative regimen (2): Penicillin G 4 MU IV q4h for 2–3 weeks OR

3.1.1.3 A Protein Synthesis Inhibitor

Preferred regimen (1): Clindamycin 900 IV mg q8h for 2–3 weeks

Preferred regimen (2): Rifampin 600 IV mg q12h for 2–3 weeks

Note: At least one antibiotic with transplacental passage is recommended.

3.1.2 Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded

3.1.2.1 A Bactericidal Antimicrobial

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks

Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks OR

3.1.2.2 A Bactericidal Agent (ß-lactam)

3.1.2.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen: Meropenem 2 g q8h for 2 weeks OR

3.1.2.2.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1): Ampicillin 3 g IV q6h for 2 weeks

Alternative regimen (2): Penicillin G 4 MU IV q4h for 2 weeks OR

3.1.2.3 A Protein Synthesis Inhibitor

Preferred regimen (1): Clindamycin 900 IV mg q8h for 2 weeks

Preferred regimen (2): Rifampin 600 IV mg q12h for 2 weeks

3.1.3 Oral antimicrobial treatment for cutaneous anthrax without systemic involvement

3.1.3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen: Ciprofloxacin 400 mg IV q8h

Note: Duration of treatment is 60 days

3.2 Treatment for anthrax in childern ^[71]

3.2.1 Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)

3.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose) for 7-10 days

Preferred regimen (2):

If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not to exceed 100 mg/dose) for 7-10 days

If patients body weight is = 45 kg: Doxycycline 100 mg/dose PO bid for 7-10 days

Preferred regimen (3): Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose) for 7-10 days

Preferred regimen (4):

If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose) for 7-10 days

If patients body weight is > 50 kg: Levofloxacin 500 mg PO qd for 7-10 days

3.2.1.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1):Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose) for 7-10 days

Alternative regimen (2): Penicillin VK 50-75 mg/kg/day PO tid or qid for 7-10 days

3.2.2 Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)

3.2.2.1 A bactericidal antimicrobial

3.2.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 14 days

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 14 days

Preferred regimen (3):

If patients body weight is < 50 kg: Levofloxacin 20 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 14 days

If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 14 days

Preferred regimen (4): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 14 days

Preferred regimen (5): Vancomycin 60 mg/kg/day IV divided q8h (follow serum concentrations) for 14 days

3.2.2.1.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 14 days

Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 14 days AND

3.2.2.2 A Protein Synthesis Inhibitor

Preferred regimen (1): Clindamycin, 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 14 days

Preferred regimen (2): (non-CNS infection dose)

If patient is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 14 days

If patient is = 12 y old: Linezolid 30 mg/kg/day IV divided q12h (not to exceed 600 mg/dose) for 14 days

Preferred regimen (3):

If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day IV loading dose (not to exceed 200 mg) THEN Doxycycline 4.4 mg/kg/day IV divided q12h (not to exceed 100 mg/dose) for 14 days

If patients body weight is =45 kg: Doxycycline 200 mg IV loading dose THEN Doxycycline 100 mg IV given q12h for 14 days

Preferred regimen (4): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 14 days

Note: Duration of therapy for 14 days or longer until clinical criteria for stability are met. Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.

3.2.3 Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older

3.2.3.1 A bactericidal antimicrobial (fluoroquinolone)

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 2–3 wks

Preferred regimen (2):

If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 2–3 wks

If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 2–3 wks

Preferred regimen (3):

If patients age is 3 months to < 2 years: Moxifloxacin 12 mg/kg/day IV, divided q12h (not to exceed 200 mg/dose) for 2–3 wks

If patients age is 2-5 years: Moxifloxacin 10 mg/kg/day IV divided q1h (not to exceed 200 mg/dose) for 2–3 wks

If patients age is 6–11 years: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks

If patients age is 12–17 years, = 45 kg body weight: Moxifloxacin 400 mg IV q24h for 2–3 wks

If patients age is 12–17 years, < 45 kg body weight: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks AND

3.2.3.2 A bactericidal antimicrobial (ß-lactam or glycopeptide)

3.2.3.2.1 For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown:

Preferred regimen (1): Meropenem 120 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 2–3 wks

Preferred regimen (2): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 2–3 wks

Preferred regimen (3): Doripenem 120 mg/kg/day IV divided q8h (not to exceed 1 g/dose) for 2–3 wks

Preferred regimen (4): Vancomycin 60 mg/kg/day IV divided q8h for 2–3 wks

3.2.3.2.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 2–3 wks

Alternative regimen (2): Ampicillin 400 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 2–3 wks AND

3.2.3.3 A Protein Synthesis Inhibitor

Preferred regimen (1):

If patients age is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 2–3 wk

If patients age is = 12 y old: Linezolid 30 mg/kg/day,IV divided q12h (not to exceed 600 mg/dose) for 2–3 wk

Preferred regimen (2): Clindamycin 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 2–3 wk

Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 2–3 wk

Preferred regimen (4): Chloramphenicol 100 mg/kg/day IV divided q6h for 2–3 wk

Note (1): Duration of therapy for 2–3 wk or greater, until clinical criteria for stability are met.Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.

Note (2): A 400-mg dose of Ciprofloxacin IV, provides an equivalent exposure to that of a 500-mg ciprofloxacin oral tablet.

3.2.4 Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)

3.2.4.1 A bactericidal antimicrobial

3.2.4.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose)

Preferred regimen (2):

If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose)

If patients body weight is = 50 kg: Levofloxacin 500 mg PO qd

3.2.4.1.2 Alternatives for penicillin-susceptible strains

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose)

Alternative regimen (2): Penicillin VK 50–75 mg/kg/day PO tid or qds AND

3.2.4.2 A protein synthesis inhibitor:

Preferred regimen (1):Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose)

Preferred regimen (2):

If the patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not exceed 100 mg/dose)

If the patients body weight is = 45 kg: Doxycycline 100 mg PO bid

Preferred regimen (3): (non-CNS infection dose):

If the patients age is < 12 yrs old: Linezolid 30 mg/kg/day PO tid

If the patients age is = 12 yrs old: Linezolid 30 mg/kg/day PO bid (not to exceed 600 mg/dose)

Note: Duration of therapy to complete a treatment course of 14 days or greater. May require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.

3.2.5 Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)

3.2.5.1 Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)

3.2.5.1.1 Bactericidal antimicrobial (fluoroquinolone) therapy

3.2.5.1.1.1 For 32–34 weeks gestational age

For 0–1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks

For 1–4 weeks of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks

3.2.5.1.1.2 For 34–37 week gestational age

For 0–1 wk of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2):Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks

For 1–4 wk of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks

3.2.5.1.1.3 Term newborn infant

For 0–1 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks

For 1–4 weeks of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks AND

3.2.5.1.2 A bactericidal antimicrobial (ß-lactam)

3.2.5.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown:

3.2.5.1.2.1.1 For 32–34 weeks gestational age

For 0–1 week of Age :

Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 wk of Age :

Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks

3.2.5.1.2.1.2 For 34–37 week gestational age

For 0–1 week of Age :

Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 week of Age :

Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks

3.2.5.1.2.1.3 Term newborn infant

For < 1 week of age

Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks

3.2.5.1.2.2 Alternatives for penicillin-susceptible strains

3.2.5.1.2.2.1 For 32–34 weeks gestational age

For 0–1 week of age

Alternative regimen (1): Penicillin G 200000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 week of age :

Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day divided IV q12h for 2–3 weeks

3.2.5.1.2.2.2 For 34–37 week gestational age

For < 1 week of age

Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 week of age

Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks

3.2.5.1.2.2.3 Term newborn infant

For 0–1 week of age

Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks

For 1–4 week of age

Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks

Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks AND

3.2.5.1.3 A protein synthesis inhibitor

3.2.5.1.3.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen (1): Linezolid 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (2): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks

3.2.5.1.3.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks

Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks

3.2.5.1.3.3 Term newborn infant

For < 1 week of age

Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks

Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks

Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h for 2–3 weeks

Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks

Note :Duration of therapy for 2–3 weeks, until clinical criteria for stability are met. Will require prophylaxis to complete an antibiotic course of upto 60 days from onset of illness.

3.2.5.2 Therapy for severe anthrax when meningitis can be ruled out

3.2.5.2.1 A bactericidal antimicrobial

3.2.5.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

3.2.5.2.1.1.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 40 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 40 mg/kg/day IV divided q12h for 2-3 weeks

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks

3.2.5.2.1.1.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks

3.2.5.2.1.1.3 Term Newborn Infant

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks

Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks

Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks

Vancomycin IV (dosing based on serum creatinine for infants of 32 wk gestational age). Follow vancomycin serum concentrations to modify dose.

If Serum creatinine < 0.7 then Vancomycin 15 mg/kg/dose IV q12h for 2-3 weeks

If Serum creatinine 0.7 -0.9 then Vancomycin 20 mg/kg/dose IV q24h for 2-3 weeks

If Serum creatinine 1–1.2 then Vancomycin 15 mg/kg/dose IV q24h for 2-3 weeks

If Serum creatinine 1.3–1.6 then Vancomycin 10 mg/kg/dose IV q24h for 2-3 weeks

If Serum creatinine > 1.6 then Vancomycin mg/kg/dose IV q48h for 2-3 weeks

Note: Begin treatment with a 20 mg/kg loading dose OR

3.2.5.2.1.2 Alternatives for penicillin-susceptible strains

3.2.5.2.1.2.1 For 32–34 weeks gestational age

For < 1 week of age

Alternative regimen (1): Penicillin G 200000 U/kg/day IV divided q12h for 2-3 weeks

Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2-3 weeks

For 1–4 week of age

Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks

3.2.5.2.1.2.2 For 34–37 week gestational age

For < 1 week of age

Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks

For 1–4 week of age

Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks
Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks

3.2.5.2.1.2.3 Term newborn infant

For < 1 week of age

Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks

Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks

For 1–4 week of age

Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks

Alternative regimen (2):Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks

3.2.5.2.2 A protein synthesis inhibitor

3.2.5.2.2.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen (1): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 wks

Preferred regimen (2): Linezolid 20 mg/kg/day IV divided q12h for 2–3 wks

Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

For 1–4 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

3.2.5.2.2.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

For 1–4 week of age

Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks

Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

3.2.5.2.2.3 Term newborn infant

For 0–1 week of age :

Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks

Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

For 1–4 week of age :

Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks

Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks

Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks

Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks

Note: Duration of therapy for 2–3 wks, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness

3.2.5.3 Oral follow-up combination therapy for severe anthrax

3.2.5.3.1 A bactericidal antimicrobial

3.2.5.3.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

3.2.5.3.1.1.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid

For 1–4 week of age

Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid

3.2.5.3.1.1.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid

For 1–4 week of age

Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid

3.2.5.3.1.1.3 Term newborn infant

For < 1 week of age

Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid

For 1–4 week of age

Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid OR

3.2.5.3.1.2 Alternatives for penicillin-susceptible strains

3.2.5.3.1.2.1 For 32–34 weeks gestational age

For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid

Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid

Alternative regimen (2): Penicillin VK 75 mg/kg/day PO bid

3.2.5.3.1.2.2 For 34–37 week gestational age

For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid

Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid

Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid

3.2.5.3.1.2.3 Term newborn infant

For < 1 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid

Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid or qid

3.2.5.3.2 A protein synthesis inhibitor

3.2.5.3.2.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen (1): Clindamycin 10 mg/kg/day PO bid

Preferred regimen (2): Linezolid 20 mg/kg/day PO bid

For 1–4 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day PO bid

Preferred regimen (2): Linezolid 30 mg/kg/day PO bid

3.2.5.3.2.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid

Preferred regimen (2): Linezolid 30 mg/kg/day PO tid

For 1–4 week of age

Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid

Preferred regimen (2): Linezolid 30 mg/kg/day PO tid

3.2.5.3.2.3 Term newborn infant

For < 1 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid

Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
Preferred regimen (3): Linezolid 30 mg/kg/day PO tid

For 1–4 week of age

Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid
Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
Preferred regimen (3): Linezolid 30 mg/kg/day PO tid

Note: Duration of therapy to complete a treatment course of 10–14 days or greater. May require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness.

3.2.5.4 Treatment of cutaneous anthrax without systemic involvement

3.2.5.4.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

3.2.5.4.1.1 For 32–34 weeks gestational age

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid

Preferred regimen (2): Clindamycin 10 mg/kg/day PO bid

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid

3.2.5.4.1.2 For 34–37 week gestational age

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid

Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid

Preferred regimen (2): Clindamycin 20 mg/kg/day PO qid

3.2.5.4.1.3 Term newborn infant

For < 1 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid

Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)

Preferred regimen (3): Clindamycin 15 mg/kg/day PO tid

For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid

Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)

Preferred regimen (3): Clindamycin 20 mg/kg/day PO qid

3.2.5.4.2 Alternatives for penicillin-susceptible strains

3.2.5.4.2.1 For 32–34 weeks gestational age

For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid

3.2.5.4.2.2 For 34–37 week gestational age

For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO bid

3.2.5.4.2.3 Term newborn infant

For < 1 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid

For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid or qid
Note : Duration of therapy for naturally acquired infection is 7–10 days and for a biological weapon–related event,may require additional prophylaxis for inhaled spores to complete an antimicrobial course of up to 60 days from onset of illness.

Bacillus anthracis, postexposure prophylaxis

1. For adults^[69]

1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

Preferred regimen (1): Ciprofloxacin 500 mg IV q12h

Preferred regimen (2): Doxycycline 100 mg IV q12h

Preferred regimen (3): Levofloxacin 750 mg IV q24h

Preferred regimen (4): Moxifloxacin 400 mg IV q24h

Preferred regimen (5): Clindamycin 600 mg IV q8h

1.2 Alternatives for penicillin-susceptible strain

Preferred regimen (1): Amoxicillin 1 g IV q8h

Preferred regimen (2): Penicillin VK 500 mg IV q6h

2. For children = 1 month^[71]

2.1 For penicillin-resistant strains or prior to susceptibility testing

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid (not to exceed 500 mg/dose)

Preferred regimen (2):

If patients body weight < 45 kg: Doxycycline 4.4 mg/kg/day, PO, bid (not to exceed 100 mg/dose)

If patients body weight > 45 kg: Doxycycline 100 mg/dose, PO, bid

Preferred regimen (3): Clindamycin 30 mg/kg/day, PO, tid (not to exceed 900 mg/dose)

Preferred regimen (4):

If patients body weight < 50 kg: Levofloxacin 16 mg/kg/day, PO, bid (not to exceed 250 mg/dose)

If patients body weight > 50 kg: Levofloxacin 500 mg, PO, qd

2.2 For penicillin-susceptible strains

Preferred regimen (1): Amoxicillin 75 mg/kg/day, PO, tid (not to exceed 1 g/dose)

Preferred regimen (2): Penicillin VK 50-75 mg/kg/day, PO, id or tid

Note: Duration of Therapy is 60 days after exposure

3. For children < 1 month

3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown

3.1.1 For 32–34 weeks gestational age

3.1.1.1 For < 1 week of Age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid

Preferred regimen (2): Clindamycin 10 mg/kg/day, PO, bid

3.1.1.2 For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO,bid

Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid

3.1.2 For 34–37 week gestational age

3.1.2.1 For < 1 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid

Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid

3.1.2.2 For 1–4 week of age

Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid

Preferred regimen (2): Clindamycin 20 mg/kg/day, PO, id

3.1.3 Term newborn infant

3.1.3.1 For < 1 week of age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid

Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)

Preferred regimen (3): Clindamycin 15 mg/kg/day, PO, tid

3.1.3.2 For 1–4 week of Age

Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid

Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)

Preferred regimen (3): Clindamycin 20 mg/kg/day, PO, qid

3.2 Alternatives for penicillin-susceptible strains

3.2.1 For 32–34 weeks gestational age

3.2.1.1 For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid

Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid

3.2.1.2 For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid

3.2.2 For 34–37 week gestational age

3.2.2.1 For < 1 week of age

Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid

Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid

3.2.2.2 For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid

3.2.3 Term newborn infant

3.2.3.1 For < 1 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid

3.2.3.2 For 1–4 week of age

Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid

Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, id or tid

Note: Duration of therapy is 60 days from exposure

Bacillus cereus Return to Top

1. Food poisoning^[72]

Preferred regimen: Food poisoning is usually self-limited and requires no antibiotic therapy.

2. Bacteremia

Preferred regimen: Vancomycin 15 mg/kg IV q12h
Alternative regimen: Clindamycin 600 mg IV q8h
Note (1): Bacillus cereus is commonly resistant to beta-lactams.
Note (2): Pseudobacteremia is transient and usually results from contaminated blood cultures, gloves, or syringes.

3. Meningitis or brain abscess

Preferred regimen: Vancomycin 15 mg/kg IV q12h
Alternative regimen: Clindamycin 600 mg IV q8h
Note: Blood culture isolates are mostly contaminates until proven otherwise, especially in intravenous drug user population.

4. Endophthalmitis

Preferred regimen: Clindamycin 450 μg intravitreal AND Gentamicin 400 μg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h
Alternative regimen: Clindamycin 600 mg IV q8h
Note: Ophthalmological consultation, culture ocular fluids, early vitrectomy, and intravitreal antibiotics are necessary.

5. Endocarditis

Preferred regimen: Vancomycin 15 mg/kg IV q12h
Note: Most blood cultures in intravenous drug users are contaminates or represent transient bacteremia.

6. Soft tissue infection

Preferred regimen: Vancomycin 15 mg/kg IV q12h
Alternative regimen: Clindamycin 600 mg IV q8h

7. Pneumonia

Preferred regimen: Vancomycin 15 mg/kg IV q12h
Alternative regimen: Clindamycin 600 mg IV q8h

Bacillus subtilis Return to Top

Bacillus subtilis infection treatment^[73]^[74]^[75]

1. Food poisoning

Preferred regimen: supportive treatment

2. Other infections

Preferred regimen: Vancomycin OR Clindamycin
Alternative regimen: Ciprofloxacin OR Imipenem
Note: Distinguish clinically significant infection from contamination before administering antibiotics.

Clostridium botulinum Return to Top

1. Antibiotics

Antibiotics are not recommended in gastrointestinal botulism due to the risk of worsening of neurological symptoms caused by the lysis of the bacteria. For wound botulism antibiotics are indicated with surgical treatment as followed:
Preferred regimen: Metronidazole 500 mg IV q8h
Alternative regimen: Penicillin G 3 million units IV q4h

2. Antitoxin ^[76]

Preferred regimen: Trivalent antitoxin (A 7,500 IU, B 5,000 IU, and E 5,000 IU) 1 vial diluted 1:10, IV infusion over 30 min
Alternative regimen: Equine antitoxin

3. General Therapy

Preferred regimen: Mechanical ventilation; IV hydration; tube feedings

Clostridium perfringens Return to Top

Clostridium perfringens ^[77]
Gas gangrene

Preferred regimen: Penicillin G 3-4 million units IV q4h AND (Clindamycin 900 mg IV q8h OR Tetracycline 500 mg IV q6h)^[78]

Clostridium tetani Return to Top

1. General measures

Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated

2. Immunotherapy

Preferred regimen: Human TIG 500 units IV/IM as soon as possible AND Age-appropriate TT-containing vaccine, 0.5 cc IM at a separate site
Note: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later

3. Antibiotic treatment^[79]

Preferred regimen: Metronidazole 500 mg IV/PO q6h OR Penicillin G 100,000–200,000 IU/kg/day IV, administered in 2–4 divided doses
Alternative regimen: Tetracyclines OR Macrolides OR Clindamycin OR Cephalosporins OR Chloramphenicol

4. Muscle spasm control

Preferred regimen: Diazepam 5 mg IV OR Lorazepam 2 mg IV titrating to achieve spasm control without excessive sedation and hypoventilation
Alternative regimen (1): Magnesium sulphate 5 g (or 75mg/kg) IV loading dose, then 2–3 g per hour until spasm control is achieved ± Benzodiazepines
Note: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased
Alternative regimen (2): Baclofen OR Dantrolene 1–2 mg/kg IV/PO q4h
Alternative regimen (3): Barbiturates 100–150 mg q1-4h by any route
Alternative regimen (4): Chlorpromazine 50–150 mg IM q4–8h
Pediatric regimen: Lorazepam 0.1–0.2 mg/kg IV q2–6h, titrating upward as needed; Barbiturates 6–10 mg/kg in children by any route; Chlorpromazine 4–12 mg IM every q4–8h
Note: As for Benzodiazepines, large amounts may be required (up to 600 mg/day); oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest

5. Autonomic dysfunction control

Preferred regimen: Magnesium sulphate OR Morphine OR Esmolol

6. Airway/respiratory control

Note: Drugs used to control spasm and provide sedation can result in respiratory depression. If spasm, including laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke spasm and exacerbate airway compromise.

Clostridium difficile Return to Top

1. Pseudomembranous colitis - mild to moderate^[80]

Preferred regimen:Metronidazole 500 mg PO tid for 10-14 days
Alternative regimen: Vancomycin 125 mg PO qid for 10-14 days
Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

2. Pseudomembranous colitis - severe^[80]

Preferred regimen: Vancomycin 125 mg PO qid for 10-14 days
Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days

3. Pseudomembranous colitis - severe, complicated^[80]

Preferred regimen: Vancomycin 125-500 mg PO qid for 10-14 days AND Vancomycin 500 mg diluted in 500 ml of saline as enema per rectum q6h AND Metronidazole 500 mg IV q8h
Note: Consider urgent surgical consult

4. Recurrent pseudomembranous colitis^[80]

First recurrence treatment

Preferred regimen: same as first episode or [Fidaxomicin]] 200 mg PO bid for 10 days

Second or more recurrence treatment

Preferred regimen: Vancomycin 125 mg PO qid for 14 days THEN Vancomycin 125 mg PO tid for 7 days THEN Vancomycin 125 mg PO bid for 7 days THEN Vancomycin 125 mg PO qd for 7 days THEN Vancomycin 125 mg PO q48h for 7 days THEN Vancomycin 125 mg PO q72h for 7 days OR Fidaxomicin 200 mg PO bid for 10 days
Note: Consider expert consult for fecal microbiota transplantation

Corynebacterium

Corynebacterium diphtheriae Return to Top

Diphtheria treatment ^[81] ^[82]

1. Antitoxin

1.1 Pharyngeal disease <48 hrs

Preferred regimen: 20,000-40,000 U IV/IM

1.2 Nasopharyngeal

Preferred regimen: 40-60,000 U IV/IM

1.3 Extensive disease, or > 72 hrs

Preferred regimen: 80-120,000 U IV/IM

Note: IV administration for severe disease

2. Antibiotics

Preferred regimen: Erythromycin 40 mg/kg/day (Maximum, 2 gm/day) PO/IV for 14 days
Alternative regimen: Procaine penicillin G 600,000 U/day IM qd for 14 days
Note: Procaine penicillin G 300,000 U/day for those weighing 10 kg or less

3. Preventive antibiotic use

Note: For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given
Preferred regimen: Benzathine penicillin G

younger than 6 years old: 600,000 U IM
6 years old and older: 1,200,000 U IM

Alternative regimen: Erythromycin

Adult: 1 g/day PO 7-10 days

Pediatric: 40 mg/kg/day PO 7-10 days

Note (1): If surveillance of contacts cannot be maintained, they should receive benzathine penicillin G
Note (2): Maintain close surveillance and begin antitoxin at the first signs of illness

Corynebacterium jeikeium Return to Top

Corynebacterium jeikeium^[83]

Preferred regimen : Vancomycin 1 gm IV q12h
Alternative regimen : Penicillin G AND Anti pseudomonal aminoglycosides like Tobramycin, Gentamicin, Amikacin

Corynebacterium urealyticum Return to Top

Corynebacterium urealyticum^[84]

1. Post renal transplant obstructive uropathy

Preferred regimen (1): Vancomycin 1 gm IV q12h
Preferred regimen (2): Teicoplanin 6 mg/kg/day IV q24h

Coxiella burnetii Return to Top

Q fever^[85]

1. Acute Q fever

1.1 Adults

Preferred Regimen: Doxycycline 100 mg PO bid for 14 days

1.2 Children

1.2.1 Children with age ≥8 years

Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum 100 mg per dose)

1.2.2 Children with age <8 years with high risk criteria

Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum: 100 mg per dose)

1.2.3 Children with age <8 years with mild or uncomplicated illness

Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 5 days (maximum 100 mg per dose).

1.2.3 Children with age < 8 years with mild or uncomplicated illness,who remains febrile past 5 days of treatment

Preferred regimen: Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (maximum: 800 mg per dose)

1.3 Pregnant women

Preferred regimen: Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO bid a day throughout pregnancy

2. Chronic Q fever

2.1 Endocarditis or vascular infection

Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for ≥18 months
Note: childern and pregnant women- consultation Recommended

2.2 Noncardiac organ disease

Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid
Note: childern and pregnant women- consultation Recommended

2.3 Postpartum with serologic profile for chronic Q fever

Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for 12 months
Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
Note (2): Post-Q fever fatigue syndrome- no current recommendation.

Ehrlichia Return to Top

1. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (adult) ^[86]

Preferred regimen: Doxycycline 100 mg PO/IV q12h for 7-14 days
Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement
Alternative regimen (1): Chloramphenicol 500mg PO qid

Alternative regimen (2): Rifampin 600 mg PO/IV qd for 7-10 days

2. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (pediatric)

2.1 ≥ 8 years old

Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 10 days

2.2 < 8 years old without Lyme disease

Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 4-5 days (or 3 days after resolution of fever)

2.3 co-infected with Lyme disease

Preferred regimen: Doxycycline (see above) THEN Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg/dose) OR Cefuroxime 30 mg/kg/day bid (Maximum, 500 mg/dose) for 14 days

Erysipelothrix rhusiopathiae Return to Top

Erysipelothrix rhusiopathiae ^[87]

1. Erysipeloid of Rosenbach (localized cutaneous infection)

Preferred regimen (1): Penicillin G benzathine 1.2 MU IV single dose
Preferred regimen (2): Penicillin VK 250 mg PO qid for 5-7 days
Preferred regimen (3): Procaine penicillin 0.6-1.2 MU IM qd for 5-7 days
Alternative regimen (1): Erythromycin 250 mg PO qid for 5-7 days
Alternative regimen (2): Doxycycline 100 mg PO bid for 5-7 days

2. Diffuse cutaneous infection

Preferred regimen: See localized infection

3. Bacteremia or endocarditis

Preferred regimen: Penicillin G benzathine 2-4 MU IV q4h for 4-6 weeks
Alternative regimen (1): Ceftriaxone 2 g IV q24h for 4-6 weeks
Alternative regimen (2): Imipenem 500 mg IV q6h for 4-6 weeks
Alternative regimen (3): Ciprofloxacin 400 mg IV q12h for 4-6 weeks
Alternative regimen (4): Daptomycin 6 mg/kg IV q24h for 4-6 weeks
Note: Recommended duration of therapy for endocarditis is 4 to 6 weeks, although shorter courses consisting of 2 weeks of intravenous therapy followed by 2 to 4 weeks of oral therapy have been successful

Listeria monocytogenes Return to Top

1. Meningitis ^[88]

Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for more than 3 weeks

Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) IV q6h for more than 3 weeks

2. Bacteremia

Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 2 weeks
Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks

3. Brain abscess or rhomboencephalitis

Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 4-6 weeks
Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks

4. Gastroenteritis

Preferred regimen (1): Amoxicillin 2g IV q4-6h
Preferred regimen (2): TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 7 days

Lactobacillus Return to Top

1. Endovascular Infection ^[89]

Preferred regiemn (1): Penicillin G 20 MU/day for 6 weeks
Preferred regiemn (2): Gentamicin 1.3 mg/kg IV q8h (trough <1.5 mg/L) AND Polychlorinated naphthalene

2. Odontogenic Infection

Preferred regiemn: Clindamycin 450 mg PO qid

3. Intrabdominal Abscess

Preferred regiemn: Clindamycin 450 mg PO qid

Leuconostoc Return to Top

Leuconostoc ^[90]

Preferred regimen (1): Penicillin G

Preferred regimen (2): Ampicillin

Alternative regimen (1): Clindamycin

Alternative regimen (2): Erythromycin

Alternative regimen (3): Minocycline

Nocardia Return to Top

1. Sulfonamide-based therapies ^[91]

1.1 Pulmonary

Preferred regimen: TMP-SMX 10 mg/kg/day (TMP) IV q6-12h for 3-6 weeks THEN 2 DS PO bid for at least 5 months

1.2 Pulmonary alternatives

Preferred regimen: Sulfisoxazole OR Sulfadiazine OR Trisulfapyrimidine 3-6 g/day PO bid-qid OR TMP-SMX 2 DS bid up to 2 DS tid

1.3 CNS (AIDS, severe or disseminated disease)

Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV for 3-6 weeks THEN 3 DS PO bid for 6-12 months

1.4 CNS alternatives

Preferred regimen: Imipenem 1000 mg IV q8h OR Ceftriaxone 2 g IV q12h OR Cefotaxime 2-3 g IV q6h AND Amikacin

1.5 Severe disease, compromised host, multiple sites

Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV AND Amikacin 7.5 mg/kg q12h OR Sulfonamide 6-12 mg/day PO

1.6 Sporotrichoid (cutaneous)

Preferred regimen: TMP-SMX 1 DS bid for 4-6 months

Note (1): Immunocompetent medicine use for 6 months; Immunosuppressed medicine for 12 months
Note (2): Treat based on host, site of disease and in vitro activity; Sulfonamide usually preferred, must treat for 6-12 months; Preferred drugs for resistant strains are Amikacin and/or Imipenem
Note (3): Seriously ill usually treated with IV Imipenem or Sulfonamide or Cefotaxime all potentially combined with Amikacin; less seriously ill treated with oral agents— especially TMP-SMX or Minocycline

2. Sulfonamide alternatives

2.1 Severe

Preferred regimen (1): (For AIDS) (Imipenem 1000 mg IV q8h OR Meropenem 2 g q8h AND Amikacin 7.5 mg/kg q12h IV
Preferred regimen (2): Cefotaxime 2-3 g q6-8h OR Ceftriaxone 2 g/day IV ± Amikacin

2.2 Mild

Preferred regimen: Minocycline 100 mg bid for at least 6 months (initial treatment of local disease or maintenance)
Alternative regimen: Amoxicillin clavulanate 875/125 mg bid OR Doxycycline OR Erythromycin OR Clarithromycin OR Linezolid OR Fluoroquinolone OR combinations for at least 6 months

Propionibacterium acnes Return to Top

Propiobacterium acnes ^[92]

1. Systemic infection

Preferred regimen: Penicillin G 2 MU IV q4h for 2-4 weeks
Alternative regimen (1): Clindamycin 600 mg IV q8h for 2-4 weeks

Alternative regimen (2): Vancomycin 15 mg/kg IV q12h for 2-4 weeks

2. Shoulder prosthesis infection

Preferred regimen: Amoxicillin AND Rifampin for 3-6 months

3. Acne vulgaris

Topical antibiotics: Erythromycin OR Clindamycin
Systemic antibiotics: Minocycline OR Doxycycline OR Trimethoprim-Sulfamethoxazole

Rhodococcus equi Return to Top

Rhodococcus equi ^[93]

First line:

Preferred regimen: Vancomycin 1 g IV q12h (15 mg/kg q12 for >70 kg) OR Imipenem 500 mg IV q6h AND Rifampin 600 mg PO qd OR Ciprofloxacin 750 mg PO bid OR Erythromycin 500 mg PO qid for at least 4 weeks or until infiltrate disappears
Note: Should be administrated at least 8 weeks in immunocompromised patients

Oral/maintenance therapy (after infiltrate clears):

Preferred regimen (1): Ciprofloxacin 750 mg PO bid

Preferred regimen (2): Erythromycin 500 mg PO qid

Alternative regimen: Azithromycin OR TMP-SMX OR Chloramphenicol OR Clindamycin
Note: Avoid Penicillins/Cephalosporins due to development of resistance; Linezolid effective in vitro, but no clinical reports of use

Rickettsia prowazekii Return to Top
Rickettsia rickettsii Return to Top

1. Adult ^[94] ^[95]

Preferred regimen: Doxycycline 100 mg q12h
Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 7-14 days
Alternative regimen: Chloramphenicol 500 mg PO qid for 7 days or stop 3 days after defervescence

2. Pediatric (under 45 kg (100 lbs))

Preferred regimen: Doxycycline 2.2 mg/kg bid
Note: The recommended dose and duration of medication needed to treat RMSF has not been shown to cause staining of permanent teeth, even when five courses are given before the age of eight. Healthcare providers should use doxycycline as the first-line treatment for suspected Rocky Mountain spotted fever in patients of all ages

Rickettsia typhi Return to Top

Bacteria – Gram-Negative Cocci and Coccobacilli

Aggregatibacter aphrophilus Return to Top

1. Endocarditis^[96]

1.1 Adults

Preferred regimen (1): Ceftriaxone 2 g/day TV/IM q24h for 4 weeks
Preferred regimen (2): Ampicillin-sulbactam 12 g/day TV q6h for 4 weeks
Preferred regimen (3): Ciprofloxacin 1000 mg PO q24h OR 800 mg/day IV q12h for 4 weeks

1.2 Pediatrics

Preferred regimen (1): Ceftriaxone 100 mg/kg/day TV/IM q24h for 4 weeks
Preferred regimen (2): Ampicillin-sulbactam 300 mg/kg/day TV q6h/q4h for 4 weeks
Preferred regimen (3): Ciprofloxacin 20-30 mg/kg/day IV/PO bid for 4 weeks
Note (1): Floroquinolone therapy recommended for patients unable to tolerate Cephalosporin and ampicillin thearpy
Note (2): For patients < 18 years, Flourouinolones are generally not recommended
Note (3): For patients with endocarditis involving the prosthetic cardiac valve or other prosthetic cardiac material should be treated for 6 weeks

2. Abscess ^[97]

The small number of patients reported and the variety of antibiotics used, do not permit identification of the optimal therapeutic regimen for this organism

Bordetella pertussis Return to Top

Brucella

Brucella Return to Top

Brucellosis ^[98],^[99]

1.Uncomplicated brucellosis in adults and children ≥8yrs of age

Preferred regimen: Doxycycline 100 mg PO bid for 6 weeks AND Streptomycin 1 g/day IM for 2-3 weeks
Alternative regimen (1): Doxycycline 100 mg/day PO for six weeks AND Gentamicin 5mg/kg IM for 7-days
Alternative regimen (2): Gentamicin 5mg/kg/day IV/ IM for 7-10 days AND Rifampicin 600–900 mg/day PO for six weeks

2. Complications of brucellosis

2.1 Spondylitis

Preferred regimen:Doxycycline for 3 months AND Streptomycin for 2 to 3 weeks.

2.2 Neurobrucellosis

Preferred regimen: Ceftriaxone 2 mg IV q12h for 1 month AND Doxycycline 100 mg PO bid for 4-5 month AND Rifampicin 600–900 mg/day PO for 4-5 month

2.3 Brucella endocarditis

Preferred regimen: Doxycycline AND an Aminoglycoside for at least 8 weeks, and therapy should be continued for several weeks after surgery when valve replacement is necessary
Note: Rifampicin OR Trimethoprim/sulfamethoxazole are used for their ability to penetrate cell membranes

3. Pregnancy

Preferred regimen: Rifampin 900 mg PO qd for 6 weeks
Note: Adding Trimethoprim-sulfamethoxazole can be considered, but this option should probably be avoided preceding the 13th week and after the 36th week of gestation because of concern about teratogenicity and kernicterus.

4.For children < 8 yrs of age

Preferred regimen (1): TMP/SMZ 8/40 mg/ kg/day PO bid for 6 weeks AND Streptomycin 30 mg/kg/day IM q24h for 3 weeks
Preferred regimen (2): Gentamicin 5 mg/kg/day IM/ IV q24h for 7-10 days
Alternative regimen (1): TMP/SMZ AND Rifampicin 15 mg/kg/day PO for 6 weeks
Alternative regimen (2): Rifampicin AND an Aminoglycoside

Eikenella corrodens Return to Top

1. Human bite/soft tissue infections ^[100]

1.1 Severe

Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
Alternative regimen (1): Doxycycline 100 mg IV bid

Alternative regimen (2): Moxifloxacin 400 mg IV q24h

Alternative regimen (3): Levofloxacin 500 mg IV q24h

1.2 Mild

Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
Alternative regimen (1): Doxycycline 100 mg PO bid

Alternative regimen (2): Moxifloxacin 400 mg PO qd

Alternative regimen (3): Levofloxacin 500 mg PO qd

2. Head and neck infections

2.1 Severe

Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
Alternative regimen (1): Doxycycline 100 mg IV bid

Alternative regimen (2): Moxifloxacin 400 mg IV q24h

Alternative regimen (3): Levofloxacin 500 mg IV q24h

2.2 Mild

Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
Alternative regimen (1): Doxycycline 100 mg PO bid

Alternative regimen (2): Moxifloxacin 400 mg PO qd

Alternative regimen (3): Levofloxacin 500 mg PO qd

3. Endocarditis

Preferred regimen (1): Ceftriaxone 1 g IV q12h

Preferred regimen (1): Cefotaxime 1-2 g IV q8h

Preferred regimen (1): Cefepime 1-2g IV q8h

Haemophilus ducreyi

Haemophilus ducreyi Return to Top

1. Chancroid^[101]

Preferred Regimen (1): Azithromycin 1 g PO in a single dose
Preferred Regimen (2): Ceftriaxone 250 mg IM in a single dose
Preferred Regimen (3): Ciprofloxacin 500 mg PO bid for 3 days
Preferred Regimen (4): Erythromycin base 500 mg PO tid for 7 days
Note: Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.
1.1 Follow-up

Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial.
Clinical resolution of fluctuant lymphadenopathy is slower than that of ulcers and might require needle aspiration or incision and drainage, despite otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage might be preferred because of reduced need for subsequent drainage procedures.

1.2 Management of sex partners

Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.

1.3 Pregnancy

Ciprofloxacin presents a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding. Alternative drugs should be used during pregnancy and lactation

1.4 HIV Infection

Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.

Haemophilus influenzae

Haemophilus influenzae Return to Top

Haemophilus influenzae^[102]

1. Non- life threatening infections^[103]

1.1 Adults

Preferred regimen (1): Amoxicillin-clavulanate 500 mg PO tid or 875 mg PO bid
Preferred regimen (2): Amoxicillin 500 mg PO tid
Preferred regimen (3): TMP-SMX DS PO bid
Preferred regimen (4): Cefuroxime 250-500 mg PO bid
Preferred regimen (5): Moxifloxacin 400 mg PO qd
Preferred regimen (6): Levofloxacin 500 mg PO qd
Preferred regimen (7): Azithromycin 500 mg PO single dose then 250 mg for 4 days

Preferred regimen (8): Clarithromycin 500 mg PO bid or XL 500 mg PO q24h
Note: Treatment duration of otitis media is 10-14 days, acute exacerbation of chronic bronchitis is 5 days (quinolone - 14 days), sinusitis is 10-14 days.

2. Meningitis^[104]

Dexamethasone 0.15 mg/kg 15-20 mins before first dose of antibiotic and then q6h for 4 days

2.1 Adults

Preferred regimen (1): Ceftriaxone 2 g IV q12h (4 g maximum)
Preferred regimen (2): Cefotaxime 2 g IV q4-6h (12 g maximum)
Preferred regimen (3): Ampicillin 2 g IV q4h if sensitive
Alternative regimen: Ciprofloxacin 400 mg IV q8h OR other Fluoroquinolones

2.2 Pediatric

2.2.1 Neonates < 7 days

2.2.1.1 Weight < 2 kg

Preferred regimen: Cefotaxime 50 mg/kg IV q12h for 10-14 days

2.2.1.2 Weight > 2 kg

Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h

Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h for 10-14 days

2.2.2 Neonates >7 days

2.2.2.1 Weight > 2 kg

Preferred regimen (1): Cefotaxime 50 mg/kg IV q6-8h
Preferred regimen (2): Ceftriaxone 75 mg/kg IV q24h for 10-14 days

2.2.3 Children

Preferred regimen (1): Cefotaxime 200 mg/kg/day IV q6h
Preferred regimen (2): Ceftriaxone 100 mg/kg IV q12-24h for 10-14 days

2.3 Post-meningitis exposure prophylaxis^[105]

Preferred regimen (1): Rifampin 600 mg PO qd for 4 days

3. Severe infections^[106]

3.1 Adults

Preferred regimen (1): Ceftriaxone 1-2 g IV q24 or q12h
Preferred regimen (2): Cefotaxime 2 g IV q6h
Alternative regimen (1): Ciprofloxacin 400 mg IV q8h or other Fluoroquinolones

Alternative regimen (2): Ampicillin 2 g IV q6h if sensitive

Neisseria gonorrhoeae

Neisseria gonorrhoeae Return to Top

Neisseria gonorrhoeae treatment^[107]

1. Gonococcal infections in adolescents and adults

1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)

1.2 Uncomplicated gonococcal infections of the pharynx

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose

1.2.1 Management of sex partners

Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present.

1.2.2 Allergy, intolerance, and adverse reactions

Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
Note: Use of ceftriaxone or cefixime is contraindicated in persons with a history of an IgE-mediated penicillin allergy (e.g., anaphylaxis, Stevens Johnson syndrome, and toxic epidermal necrolysis).

1.2.3 Pregnancy

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose

1.2.4 Suspected cephalosporin treatment failure

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
Note: Treatment failure should be considered in: (1) persons whose symptoms do not resolve within 3–5 days after appropriate treatment and report no sexual contact during the post-treatment follow-up period; (2) persons with a positive test-of-cure (i.e., positive culture ≥ 72 hours or positive NAAT ≥ 7 days after receiving recommended treatment) when no sexual contact is reported during the post-treatment follow-up period; (3) persons who have a positive culture on test-of-cure (if obtained) if there is evidence of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the post-treatment follow-up period.

1.3 Gonococcal conjunctivitis

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose

Note: Consider one-time lavage of the infected eye with saline solution.

1.3.1 Management of sex partners

Patients should be instructed to refer their sex partners for evaluation and treatment.

1.4 Disseminated gonococcal infection

1.4.1 Arthritis and arthritis-dermatitis syndrome

Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
Alternative regimen (1): Cefotaxime 1 g IV q8h for 7 days
Alternative regimen (2): Ceftizoxime 1 g IV q8h for 7 days AND Azithromycin 1 g PO in a single dose

1.4.2 Gonococcal meningitis and endocarditis

Preferred regimen: Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose

2. Gonococcal infections among neonates

2.1 Ophthalmia neonatorum caused by N. gonorrhoeae

Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg

2.1.1 Management of mothers and their sex partners

Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).

2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates

Preferred regimen (1): Ceftriaxone 25-50 mg/kg/day IM/IV q24h for 7 days
Preferred regimen (2): Cefotaxime 25 mg/kg IM/IV q12h for 7 days.
Note (1): The duration of treatment is 10-14 days if meningitis is documented.
Note (2): Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely.

2.2.1 Management of mothers and their sex partners

Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).

2.3 Neonates born to mothers who have gonococcal infection

Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg

2.3.1 Management of mothers and their sex partners

Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.

3. Gonococcal infections among infants and children

3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis

Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg

3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis

Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)

3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis

Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days

3.4 Children who weigh > 45 kg and who have bacteremia or arthritis

Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days

Neisseria meningitidis

Neisseria meningitidis Return to Top

1. Meningococcal meningitis or meningococcemia, treatment^[4]^[108]

1.1 Adults

1.1.1 Penicillin MIC < 0.1 mcg/mL

Preferred regimen (1): Penicillin G 4 MU IV q4h for 7 days
Preferred regimen (2): Ampicillin 2 g IV q4h for 7 days
Alternative regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
Alternative regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
Alternative regimen (3): Chloramphenicol 4-6 g/day IV q6h for 7 days

1.1.2 Penicillin MIC 0.1-1.0 mcg/mL

Preferred regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
Preferred regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
Alternative regimen (1): Cefepime 2 g IV q8h for 7 days
Alternative regimen (2): Chloramphenicol 4-6 g/day IV q6h for 7 days
Alternative regimen (3): Moxifloxacin 400 mg IV q24h for 7 days
Alternative regimen (4): Meropenem 2 g IV q8h for 7 days

1.2 Neonates (birth-7 days old)

1.2.1 Penicillin MIC < 0.1 mcg/mL

Preferred regimen (1): Penicillin G 0.15 MU/kg/day IV q8-12h for 7 days
Preferred regimen (2): Ampicillin 150 mg/kg/day IV q8h for 7 days
Alternative regimen (1): Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
Alternative regimen (2): Chloramphenicol 25 mg/kg/day IV q24h for 7 days

1.2.2 Penicillin MIC 0.1-1.0 mcg/mL

Preferred regimen: Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
Alternative regimen: Chloramphenicol 25 mg/kg/day IV q24h for 7 days

1.3 Neonates (8-28 days old)

1.3.1 Penicillin MIC < 0.1 mcg/mL

Preferred regimen (1): Penicillin G 0.2 MU/kg/day IV q6-8h for 7 days
Preferred regimen (2): Ampicillin 200 mg/kg/day IV q6-8h for 7 days
Alternative regimen (1): Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
Alternative regimen (2): Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days

1.3.2 Penicillin MIC 0.1-1.0 mcg/mL

Preferred regimen : Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
Alternative regimen : Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days

1.4 Infants and children

1.4.1 Penicillin MIC < 0.1 mcg/mL

Preferred regimen (1): Penicillin G 0.3 MU/kg/day IV q4-6h for 7 days
Preferred regimen (2): Ampicillin 300 mg/kg/day IV q6h for 7 days
Alternative regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
Alternative regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
Alternative regimen (3): Chloramphenicol 75-100 mg/kg/day IV q6h for 7 days

1.4.2 Penicillin MIC 0.1-1.0 mcg/mL

Preferred regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
Preferred regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
Alternative regimen (1): Cefepime 150 mg/kg/day IV q8h for 7 days
Alternative regimen (2): Chloramphenicol 75-100 mg/kg/day q6h for 7 days
Alternative regimen (3): Meropenem 120 mg/kg/day IV q8h for 7 days

Note (1): Dexamethasone has not been shown to be beneficial in meningococcal meningitis and should be discontinued once this diagnosis is established.^[109]^[110]
Note (2): Clinical data are limited on the use of fluoroquinolones for therapy for meningococcal meningitis but may be considered in patients not responding to standard therapy or when disease is caused by resistant organisms.

2. Meningococcal meningitis, prophylaxis for household and close contacts^[111]

2.1 Adults

Preferred regimen (1): Rifampin 600 mg PO bid for 2 days
Preferred regimen (2): Ciprofloxacin 500 mg PO single dose
Preferred regimen (3): Ceftriaxone 250 mg IM single dose

2.2 Children < 15 years

Preferred regimen: Ceftriaxone 12 mg IM single dose

2.3 Children ≥ 1 month

Preferred regimen: Rifampin 10 mg /kg PO bid for 2 days

2.4 Children < 1 month

Preferred regimen: Rifampin 5 mg/kg PO bid for 2 days

Moraxella catarrhalis Return to Top

Moraxella catarrhalis ^[112]

Preferred regimen(1): TMP-SMX 1DS PO bid
Preferred regimen(2): Erythromycin 500 mg PO qid
Preferred regimen(3): Clarithromycin 500 mg PO bid or XL 1 g PO qd
Preferred regimen(4): Azithromycin 500 mg PO single dose THEN 250 mg PO qd
Preferred regimen(5): Doxycycline 100 mg PO/IV bid/q12h
Preferred regimen(6): Cefprozil 200-500 mg PO bid

Preferred regimen(7): Cefpodoxime 200-400 mg PO bid

Preferred regimen(8): Cefuroxime 250-500 mg PO bid

Preferred regimen(9): Cefdinir 300 mg PO bid
Preferred regimen(10): Moxifloxacin 400 mg IV/PO qd

Preferred regimen(11): Levofloxacin 500 mg IV/PO qd
Preferred regimen(12): Amoxicillin clavulanate 875/125 mg PO bid or XL 2000/125 PO bid

Pasteurella multocida Return to Top

Pasteurella multocida ^[113]

Preferred regimen (1): Amoxicillin clavulanate 500 mg PO tid or 875 mg PO bid with food
Note: Its also a preferred empirical coverage of animal bite wounds
Preferred regimen (2): Ampicillin sulbactam 3 g IV q6h
Preferred regimen (3): Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
Preferred regimen (4): Levofloxacin 500 mg PO qd or IV q24h
Alternative regimen (1): Doxycycline 100 mg PO bid
Alternative regimen (2): TMP-SMX DS PO bid (for beta-lactam allergic patients )
Alternative regimen (3): Penicillin 500 mg PO qid or 4 MU IV q4h (use only if isolate known to be susceptible)

Bacteria – Spirochetes

Borrelia burgdorferi Return to Top

Lyme disease ^[114]

1. Early Lyme Disease

1.1 Erythema migrans

1.1.1 Adult

Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
Preferred regimen (2): Amoxicillin 500 mg PO tid for 14-21 days
Preferred regimen (3): Cefuroxime axetil 500 mg bid for 14-21 days
Alternatie regimen (1): Azithromycin 500 mg PO qd for 7–10 days
Alternatie regimen (2): Clarithromycin 500 mg PO bid for 14–21 days (if the patient is not pregnant)

Alternatie regimen (3): Erythromycin 500 mg PO qid for 14–21 days

1.1.2 Pediatric

1.1.2.1 children <8 years of age

Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h (Maximum of 500 mg per dose)

Preferred regimen (2): Cefuroxime axetil 30 mg/kg/day PO q12h（Maximum, 500 mg per dose)

1.1.2.2 children ≥8 years of age

Preferred regimen (1): Doxycycline 4 mg/kg/day PO q12h（Maximum, 100 mg per dose）
Preferred regimen (2): Azithromycin 10 mg/kg PO qd (Maximum, 500 mg qd)

Preferred regimen (3): Clarithromycin 7.5 mg/kg PO bid (Maximum, 500 mg per dose)

Preferred regimen (4): Erythromycin 12.5 mg/kg PO qid (Maximum, 500 mg per dose)

1.2 When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis

Preferred regimen: Amoxicillin-Clavulanate 500 mg PO tid
Pediatric regimen: Amoxicillin-Clavulanate 50 mg/kg/day q8h (Maximum, 500 mg per dose)

1.3 Lyme meningitis and other manifestations of early neurologic Lyme disease

1.3.1 Adult

Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
Alternative regimen (1): Cefotaxime 2 g IV q8h
Alternative regimen (2): Penicillin G 18–24 MU q4h (for patients with normal renal function)
Alternative regimen (3): Doxycycline 200–400 mg/day PO bid for 10–28 days

1.3.2 Pediatric

Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV single dose (Maximum, 2 g)
Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6-8h (Maximum, 6 g per day)
Alternative regimen (1): Penicillin G 200,000–400,000 units/kg/day IV q4h (for normal renal function) (maximum, 18–24 MU per day)
Alternative regimen (2): Doxycycline 4–8 mg/kg/day PO bid (maximum, 100–200 mg per dose) (≥8 years old)

1.4 Lyme carditis

Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
Note: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)

1.5 Borrelial lymphocytoma

Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)

2. Late Lyme Disease

2.1 Lyme arthritis

Preferred regimen (1): Doxycycline 100 mg PO bid

Preferred regimen (2): Amoxicillin 500 mg PO tid
Alternative regimen: Cefuroxime axetil 500 mg PO bid for 28 days
Pediatric regimen: Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg per dose); Cefuroxime axetil 30 mg/kg/day bid (Maximum,500 mg per dose); (≥8 years of age) Doxycycline 4 mg/kg/day bid (Maximum, 100 mg per dose)
Note: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4 weeks course of Ceftriaxone IV

2.2 patients with arthritis and objective evidence of neurologic disease

Preferred regimen: Ceftriaxone IV for 2–4 weeks
Alternative regimen (1): Cefotaxime IV

Alternative regimen (1): Penicillin G IV
Pediatric regime: Ceftriaxone; Cefotaxime; Penicillin G IV

2.3 Late neurologic Lyme disease

Preferred regimen: Ceftriaxone IV for 2 to 4 weeks
Alternative regimen (1): Cefotaxime IV

Alternative regimen (2): Penicillin G IV
Pediatric regimen: Ceftriaxone; Cefotaxime; Penicillin G

2.4 Acrodermatitis chronica atrophicans

Preferred regimen (1): Doxycycline 100 mg PO bid for 21 days
Preferred regimen (2): Amoxicillin 500 mg PO tid for 21 days
Preferred regimen (3): Cefuroxime axetil 500 mg PO bid for 21 days

3. Post–Lyme Disease Syndromes

Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)

Borrelia recurrentis Return to Top

1. Tick-Borne Relapsing Fever ^[115]

Preferred regimen: Doxycycline 100 mg PO bid for 5-10 days
Alternative regimen: Erythromycin 500 mg PO qid for 5-10 days
Note: If meningitis/encephalitis present, use Ceftriaxone 2 g IV q12h for 14 days

2. Louse-Borne Relapsing Fever

Preferred regimen: Tetracycline 500 mg PO single dose
Alternative regimen: Erythromycin 500 mg PO single dose

Leptospira Return to Top

1. Severe ^[116] ^[117]

Preferred regimen: Penicillin 1.5 MU IV q6h for 5-7 days

2. Less severe

Preferred regimen (1): Amoxycillin

Preferred regimen (2): Ampicillin

Preferred regimen (3): Doxycycline 100 mg IV/PO q12h/bid for 5-7 days

Preferred regimen (4): Erythromycin

Preferred regimen (5): Ceftriaxone 1 g IV q24h for 5-7 days

Preferred regimen (6): Cefotaxime

Preferred regimen (7): Quinolone PO

Treponema pallidum Return to Top

1. Syphilis Among non-HIV-Infected Persons ^[118]

1.1 Primary and Secondary Syphilis

Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose

1.2 Latent Syphilis

1.2.1 Early Latent Syphilis

Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose

1.2.2 Late Latent Syphilis or Latent Syphilis of Unknown Duration

Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
Pediatric regimen: Benzathine penicillin G 50,000 U/kg IM (Maximum, 2.4 MU), administered as 3 doses at 1 week intervals (total 150,000 U/kg up to the adult total dose of 7.2 MU)

1.3 Tertiary Syphilis

Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals

1.4 Neurosyphilis and ocular syphilis

Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days

2. Syphilis Among HIV-Infected Persons

2.1 Primary and Secondary Syphilis Among HIV-Infected Persons

Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose

2.2 Latent Syphilis Among HIV-Infected Persons

2.2.1 early latent

Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose

2.2.2 late latent

Preferred regimen: Benzathine penicillin G 2.4 MU once a week for 3 weeks

2.3 Neurosyphilis Among HIV-Infected Persons

Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days

3. Syphilis During Pregnancy

Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection

4. Congenital Syphilis in neonates

4.1 condition1: Infants with proven or highly probable disease and (1) an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer; or（3）a positive darkfield test of body fluid(s).

Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days

Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.

4.2 condition2: Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was not treated, inadequately treated, or has no documentation of having received treatment; (2) mother was treated with erythromycin or another nonpenicillin regimen; or (3) mother received treatment <4 weeks before delivery.

Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days

Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days

Preferred regimen (3): Benzathine penicillin G 50,000 U/kg/dose IM single dose
Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered

4.3 condition3: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and (2) mother has no evidence of reinfection or relapse.

Preferred regimen: Benzathine penicillin G 50,000 U/kg/dose IM single dose

4.4 condition4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother's treatment was adequate before pregnancy; and (2) mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).

No treatment is required
Benzathine penicillin G 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain.

5. Congenital Syphilis in infants and children

Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days

Bacteria – Gram-Negative Bacilli

Achromobacter xylosoxidans Return to Top

Acinetobacter baumannii

Acinetobacter baumannii Return to Top

Acinetobacter baumannii^[119]

Preferred regimen (1): Imipenem 0.5-1 g IV q6h
Preferred regimen (2): Ampicillin/sulbactam 3 g IV q4h
Preferred regimen (3): Cefepime 1-2 g IV q8h
Preferred regimen (4): Colistin 2.5 mg/kg IV q12h
Preferred regimen (5): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h or 15 mg/kg IV q24h
Preferred regimen (7) (pan-resistant isolates): Colistin 5 mg/kg/day IV q12h ± Imipenem
Preferred regimen (8) (pan-resistant isolates): Ampicillin-sulbactam 3 g IV q4h
Alternative regimen (1): Ceftriaxone 1-2 g IV qd
Alternative regimen (2): Cefotaxime 2-3 g IV q6-8h
Alternative regimen (3): Ciprofloxacin 400 mg IV q8-12h or 750 mg PO bid
Alternative regimen (4): TMP-SMX 15-20 mg (TMP)/kg/day IV q6-8h or 2 DS PO bid

Aeromonas hydrophila

Aeromonas hydrophila Return to Top

Aeromonas hydrophila ^[120]

1. Diarrhea

Preferred regimen (if not self-limiting, or if severe): Ciprofloxacin 500 mg PO bid.
Alternate regimen: TMP-SMX 1 DS PO bid
Note: High resistance to sulfa agents described in Taiwan and Spain

2. Skin and soft tissue infection

2.1 Mild infection

Preferred regimen (1): Ciprofloxacin 500 mg PO bid
Preferred regimen (2): Levofloxacin 500 mg qd

2.2 Severe infection or sepsis

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h
Preferred regimen (2): Levofloxacin 750 mg IV q24h
Note (1): For suspicion of water-based injury,empiric coverage for Vibrio doxycycline 100 mg bid, although flouroquinolones may also cover and vancomycin 15 mg/kg IV q12h with or without clindamycin or linezolid for inhibition of gram-positive toxin production
Note (2): Alternatives to fluoroquinolones for Aeromonas coverage include carbapenems (ertapenem, doripenem, imipenem or meropenem), ceftriaxone, cefepime and aztreonam

3. Prevention

Preferred regimen: Frequent recommendations include using a Cephalosporin (e.g.,cefuroxime,ceftriaxone or cefixime) OR a Fluoroquinolone (e.g.,ciprofloxacin or levofloxacin) during treatment with medicinal leeches
Note (1): Duration of antibiotic use is 3-5 days, some recommend continuing until wound or eschar resolves
Note (2): Aeromonas isolates from leeches have been described as uniformly susceptible to fluoroquinolones

Bartonella

Bartonella Return to Top

Bartonella^[121]

1. Bartonella quintana

1.1 Acute or chronic infections without endocarditis^[122]

Preferred regimen: Doxycycline 200 mg PO qd or 100 mg bid for 4 weeks AND Gentamicin 3 mg/kg IV qd for the first 2 weeks

1.2 Endocarditis^[11]

Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

2. Bartonella elizabethae

2.1 Endocarditis^[11]

Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks

3. Bartonella bacilliformis

3.1 Oroya fever

Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
Note: If severe disease, add Ceftriaxone 1 g IV qd for 14 days

3.2 Verruga peruana^[123]

Preferred regimen: Azithromycin 500 mg PO qd for 7 days
Alternative regimen (1): Rifampin 600 mg PO qd for 14-21 days
Alternative regimen (2): Ciprofloxacin 500 mg bid for 7-10 days

4. Bartonella henselae^[124]

4.1 Cat scratch disease

No treatment recommended for typical cat scratch disease, consider treatment if there is an extensive lymphadenopathy
4.1.1 If extensive lymphadenopathy

Preferred regimen (1) (pediatrics): Azithromycin 500 mg PO on day 1 THEN 250 mg PO qd on days 2 to 5
Preferred regimen (2) (adults): Azithromycin 1 g PO at day 1 THEN 500 mg PO for 4 days

4.2 Endocarditis

Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6weeks ± Doxycycline 100 mg PO bid for 6 weeks

4.3 Retinitis

Preferred regimen: Doxycycline 100 mg bid AND Rifampin 300 mg bid PO for 4-6 weeks

4.4 Bacillary angiomatosis^[125]

Preferred regimen (1): Erythromycin 500 mg PO qid for 2 months at least
Preferred regimen (2): Doxycycline 100 mg PO bid for 2 months at least

4.5 Bacillary Pelliosis^[125]

Preferred regimen (1): Erythromycin 500 mg PO qid for 4 months at least
Preferred regimen (2): Doxycycline 100 mg PO bid for 4 months at least

Bordetella pertussis

Bordetella pertussis Return to Top

Bordetella pertussis^[126]

1. Whooping cough

1.1 Adults

Preferred regimen (1): Azithromycin 500 mg PO single dose on day 1 THEN 250 mg PO qd on 2-5 days
Preferred regimen (2): Erythromycin 2 g/day PO qid for 14 days
Preferred regimen (3): Clarithromycin 1 g PO bid for 7 days.
Alternative regimen (intolerant of macrolides): Trimethoprim 320 mg/day AND Sulfamethoxazole 1600 mg/day PO bid for 14 days

1.2 Infants <6 months of age

1.2.1 Infants <1 month

Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
Preferred regimen (2) (if azithromycin unavailable): Erythromycin 40-50 mg/kg/day PO q6h for 14 days
Note: TMP-SMX contraindicated for infants aged < 2 months

1.2.2 Infants of 1-5 months of age

Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
Preferred regimen (2): Erythromycin 40-50 mg/kg/day PO qid for 14 days
Preferred regimen (3): Clarithromycin 15 mg/kg PO bid for 7 days
Alternative regimen: For infants aged ≥ 2 months TMP 8 mg/kg q24h AND SMX 40 mg/kg/day PO bid for 14 days

1.3 Infants ≥6 months of age-children

Preferred regimen(1): Azithromycin 10 mg/kg single dose THEN 5 mg/kg (500 mg Maximum) qd for 2-5 days
Preferred regimen(2): Erythromycin 40-50 mg/kg PO (2 g daily Maximum) qid for 14 days
Preferred regimen(3): Clarithromycin 15 mg/kg PO (1 g daily Maximum) bid for 7 days
Preferred regimen(4): TMP 8 mg/kg/day AND SMX 40 mg/kg/day bid for 14 days

2. Post exposure prophylaxis^[127]

Preferred regimen: The antibiotic regimens for post exposure prophylaxis are similar to the regimens used for the treatment of pertussis
Note (1): Post exposure prophylaxis to an asymptomatic contacts within 21 days of onset of cough in the index patient can potentially prevent symptomatic infection
Note (2): Close contacts include persons who have direct contact with respiratory, oral or nasal secretions from a symptomatic patient (eg: cough, sneeze, sharing food, eating utensils, mouth to mouth resuscitation, or performing a medical examination of the mouth, nose, throat.
Note (3): Some close contacts are at high risk for acquiring severe disease following exposure to pertussis. These contacts include infants aged < 1 year , persons with some immunodeficiency conditions, or other underlying medical conditions such as chronic lung disease, respiratory insufficiency and cystic fibrosis.

Burkholderia cepacia

Burkholderia cepacia Return to Top

Burkholderia cepacia complex^[128]

Preferred regimen (1): Ceftazidime 2 g IV q8h
Preferred regimen (2): Imipenem 1 g IV q6h
Preferred regimen (3): Meropenem 1-2 g IV q8h
Preferred regimen (4): Minocycline 100 mg IV/PO bid

Burkholderia pseudomallei

Burkholderia pseudomallei Return to Top

Burkholderia pseudomallei

1. Melioidosis^[129]

1.1 Intial intensive therapy (Minimum of 10-14 days)

Preferred regimen (1): Ceftazidime 50 mg/kg upto 2 g q6h
Preferred regimen (2): Meropenem 25 mg/kg upto 1 g q8h
Preferred regimen (3): Imipenem 25 mg/kg upto 1 g q6h
Note: Any one of the three may be combined with TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h (recommended for neurologic, bone, joint, cutaneous and prostatic melioidosis)

1.2 Eradication therapy (Minimum of 3 months)

Preferred regimen: TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h

Campylobacter fetus

Campylobacter fetus Return to Top

Campylobacter fetus^[130]

1. Gastroenteritis

Preferred regimen: Gentamicin 5 mg/kg IV q24h
Alternative regimen (1): Ampicillin 100 mg/kg IV q6h

Alternative regimen (2): Imipenem 500 mg IV q6h

Campylobacter jejuni Return to Top

Campylobacter jejuni

1. Gastroenteritis^[131]

Most patients donot require antibiotics and symptoms last < 1 week
1.1 Indications for the treatment

Highfevers
Bloodystools
Prolonged illness > 1 week
Pregnancy
HIV and other immunosuppressed states

1.2 Treatment regimen ^[132]

Preferred regimen (1):Erythromycin stearate 500 mg PO bid for 5 days
Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 3–5 days
Alternative regimen (1): TMP-SMX DS PO bid for 3–5 days
Note (1): Campylobacter resistance to TMP-SMX common in tropics
Note (2): Extraintestinal infections should be treated for longer duration (e.g.,2-4 weeks)

Capnocytophaga canimorsus

Capnocytophaga canimorsus Return to Top

Capnocytophaga canimorsus^[133]

1. Severe cellulitis/sepsis or endocarditis

Preferred regimen (1) (Beta-lactam/beta-lactamase inhibitor): Ampicillin/sulbactam 3 g IV q6h
Preferred regimen (2) (Non-beta-lactamase producing): Penicillin G 2-4 MU IV q24h
Alternative regimen (1): Ceftriaxone 1-2 g IV q24h
Alternative regimen (2): Meropenem 1 g IV q8h
Alternative regimen (3) (complicated infections or immunocompromise): Clindamycin 600 mg IV q8h may be combined with above agents
Note (1): Resistance to aztreonam described, and variable susceptibility reported to TMP-SMX and aminoglycosides
Note (2): For endocarditis, alternatives to penicillins not well established, treated for duration of 6 weeks
Note (3): For non-endocarditis infections, duration not well established, but most authorities recommend at least 14-21 days of therapy

2. Mild cellulitis/dog or cat bites

Preferred regimen (1): Amoxicillin/clavulanate 500 mg PO q8h or 875 mg PO bid
Preferred regimen (2): Amoxicillin 500 mg PO q8h
Alternative regimen (1): Clindamycin 300 mg PO q6h
Alternative regimen (2): Doxycycline 100 mg PO bid
Alternative regimen (3): Clarithromycin 500 mg PO bid
Alternative regimen (4): Moxifloxacin 400 mg PO qd

3. Meningitis or brain abscess

Preferred regimen (1): Ceftriaxone 2 g IV q12h AND Ampicillin 2 g IV q4h
Preferred regimen (2) (if beta-lactamase producing or polymicrobial brain abscess): Imipenem/Cilastin 1000 mg q6-8h AND Clindamycin 600 mg IV q8h

4. Prevention

Although no firm data supports this recommendation, many clinicians do give prophylaxis for dog and cat bites in asplenic patients with Amoxicillin/clavulanate for 7-10 days.

Citrobacter freundii

Citrobacter freundii Return to Top

Citrobacter freundii^[134]

Preferred regimen (1): Meropenem 1-2 g IV q8h
Preferred regimen (2): Imipenem 1 g IV q6h
Preferred regimen (3): Doripenem 500 mg IV q8h
Preferred regimen (4): Cefepime 1-2 g IV q8h
Preferred regimen (5): Ciprofloxacin 400 mg IV q12h or 500 mg PO bid for UTI
Preferred regimen (6): Gentamicin 5 mg/kg IV q24h
Alternate regimen (1): Piperacillin-tazobactam 3.375 mg IV q6h
Alternate regimen (2): Aztreonam 1-2 g IV q6h
Alternate regimen (3): TMP-SMX 5 mg/kg q6h IV or DS PO bid for UTI
Note: Usually carbenicillin sensitive, cephalothin resistant

Citrobacter koseri

Citrobacter koseri Return to Top

Citrobacter koseri^[135]

Preferred regimen (1): Ceftriaxone 1-2 g IV q12-24h
Preferred regimen (2): Cefotaxime 1-2 g IV q6h
Preferred regimen (3): Cefepime 1-2 IV q8h
Alternate regimen (1): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h for UTI
Alternate regimen (2): Imipenem 1 g IV q6h
Alternate regimen (3): Doripenem 500 mg IV q8h
Alternate regimen (4): Meropenem 1-2 g IV q8h
Alternate regimen (5): Aztreonam 1-2 g IV q6h
Alternate regimen (6): TMP-SMX 5 mg/kg IV q6h or DS PO bid for UTI
Note: Usually Ampicillin resistant, but may be sensitive to first generation cephalosporins

Elizabethkingia meningoseptica Return to Top

1. Bacteremia^[136]^[137]

Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
Preferred regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
Alternative regimen (1): Ciprofloxacin 400 mg IV q12h
Alternative regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h

Enterobacter

Enterobacter Return to Top

Enterobacter species including E. aerogenes and E. cloacae^[138]^[139]^[140]^[141]^[142]

1. Empiric antimicrobial therapy pending in vitro susceptibility

1.1 Non–life-threatening infections or MDR-GNB prevalence < 20%

Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h ± Aminoglycosides
Alternative regimen: Ciprofloxacin 400 mg IV q8–12h

1.2 Life-threatening infections or MDR-GNB prevalence > 20%

Preferred regimen: Meropenem 0.5–1 g IV q8h
Alternative regimen (1): Colistin AND Meropenem 0.5–1 g IV q8h
Alternative regimen (2): Colistin AND Imipenem 500 mg IV q6h
Alternative regimen (3): Colistin AND Doripenem 500 mg IV q8h
Alternative regimen (4): Colistin AND Ertapenem 1 g IV q24h
Alternative regimen (5): Colistin AND Fosfomycin 6 g IV q6h

2. In vitro susceptibility available

2.1 Susceptible to all tested agents

Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h
Alternative regimen (1): Ciprofloxacin 400 mg IV q8–12h
Alternative regimen (2): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)

2.2 Extended spectrum beta-lactamase (ESBL)-producing Enterobacter spp.

Preferred regimen: Meropenem 0.5–1 g IV q8h
Alternative regimen (1): Imipenem 500 mg IV q6h
Alternative regimen (2): Doripenem 500 mg IV q8h
Alternative regimen (3): Ertapenem 1 g IV q24h
Alternative regimen (4): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)

2.3 Resistant to all tested agents

Preferred regimen: Colistin AND Meropenem 0.5–1 g IV q8h
Alternative regimen (1): Colistin AND Imipenem 500 mg IV q6h
Alternative regimen (2): Colistin AND Doripenem 500 mg IV q8h
Alternative regimen (3): Colistin AND Ertapenem 1 g IV q24h
Alternative regimen (4): Colistin AND Minocycline 100 mg IV q12h

Escherichia coli

Escherichia coli Return to Top

Escherichia coli^[143]

1. Meningitits

Preferred regimen (1): Ceftriaxone 4 g IV q12–24h
Preferred regimen (2): Cefotaxime 8–12 g/day IV q4–6h
Alternative regimen (1): Aztreonam 6–8 g/day IV q6–8h
Alternative regimen (2): Gatifloxacin 400 mg/day IV q24h
Alternative regimen (3): Moxifloxacin 400 mg/day IV q24h
Alternative regimen (4): Meropenem 6 g/day IV q8h
Alternative regimen (5): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day IV q6–12h
Alternative regimen (6): Ampicillin 12 g/day IV q4h

2. Uncomplicated urinary tract infection^[144]

Preferred agents (IDSA/AUA Guidelines): TMP-SMX DS PO bid for 3 days
Alternative regimen (1): Ciprofloxacin 250 mg PO bid
Alternative regimen (2): Ciprofloxacin 500 mg XR qd for 3 days
Alternative regimen (3): Levofloxacin 250 mg PO qd for 3 days.
Alternative regimen (4): Nitrofurantoin 100 mg PO q6h
Alternative regimen (5): Nitrofurantoin macrocrystals 100 mg PO bid for 7 days
Alternative regimen (6): Fosfomycin 3 g sachet PO single dose
Note: For older patients, those with comorbidities (e.g., diabetes mellitus) use 7-10 days course.

3. Pyelonephritis

3.1 Acute uncomplicated pyelonephritis^[145]

Preferred regimen (1): Ciprofloxacin 500 mg bid PO for 5-7 days
Preferred regimen (2): Ciprofloxacin-Erythromycin 1000 mg q24h
Preferred regimen (3): Levofloxacin 750 mg q24h
Preferred regimen (4): Ofloxacin 400 mg bid
Preferred regimen (5): Moxifloxacin 400 mg q24h
Alternative regimen (1): Amoxicillin-Clavulanic acid 875/125 mg PO q12h or 500/125 mg PO tid or 1000 /125 mg PO bid
Alternative regimen (2): Oral Cephalosporins
Alternative regimen (3): TMP-SMX 2 mg/kg IV q6h PO for 14 days

3.2 Acute pyelonephritis (Hospitalized)^[146]

Preferred regimen (1): Ciprofloxacin 400 mg IV q12h
Preferred regimen (2): Ampicillin and Gentamicin
Preferred regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h for 14 days
Alternative regimen (1): Ticarcillin-Clavulanate 3.1 g IV q6h
Alternative regimen (2): Ampicillin-Sulbactam 3 g IV q6h
Alternative regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h
Alternative regimen (4): Ertapenem 1 g IV q24h
Alternative regimen (5): Doripenem 500 mg q8h for 14 days

4. Traveler’s diarrhea^[147]

4.1 Prophylaxis

Preferred regimen (1): Bismuth subsalicylate two chewable tablets qid

Preferred regimen (2): Norfloxacin 400 mg PO qd

Preferred regimen (3): Ciprofloxacin 500 mg PO qd

Preferred regimen (4): Rifaximin 200 mg PO qd or bid

4.2 Symptomatic treatment

Preferred regimen (1): Bismuth subsalicylate 1 oz PO every 30 min for 8 doses

Preferred regimen (2): Loperamide 4 mg PO then 2 mg after each loose stool not to exceed 16 mg daily

4.3 Antibiotic treatment

Preferred regimen (1): Fluoroquinolones, Norfloxacin 400 mg PO bid

Preferred regimen (2): Ciprofloxacin 500 mg PO bid

Preferred regimen (3): Ofloxacin 200 mg PO bid

Preferred regimen (4): Levofloxacin 500 mg PO qd

Preferred regimen (5): Azithromycin 1000 mg PO single dose

Preferred regimen (6): Rifaximin 200 mg PO tid

5. Malacoplakia^[148]

Preferred regimen (1): Bethanechol chloride AND Ciprofloxacin 400 mg IV q12h
Preferred regimen (2): Bethanechol chloride AND TMP-SMX 2 mg/kg (TMP component IV q6h)

6. Bacteremia/pneumonia^[149]

Preferred regimen (1): Ceftriaxone 1-2 g IV q24h
Preferred regimen (2): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h
Preferred regimen (3): Levofloxacin 500 mg PO/IV q24h
Preferred regimen (4): Moxifloxacin 400 mg IV/PO q24h
Preferred regimen (5): Ampicillin 2 g IV q6h (if sensitive)
Preferred regimen (6): TMP-SMX 5-10 mg/kg/day for q6-8h IV (if sensitive)
Alternative regimen (1): Imipenem, Meropenem, Ertapenem, Doripenem; Ceftazidime, Cefepime; Cefazolin or Cefuroxime (if sensitive); Aztreonam; Ticarcillin, Piperacillin; Piperacillin-Tazobactam
Alternative regimen (2): Ampicillin-sulbactam 3 g IV q6h AND (Gentamicin 1.5 mg/kg IV q8h or 5-7 mg/kg/day IV OR Tobramycin 5 mg/kg/day IV)
Note (1): A 7- to 14-day course of antibiotic therapy is usually recommended.
Note (2): The choice of antimicrobial agents should be based on susceptibility results.
Note (3): Monotherapy with aminoglycosides is generally not recommended for bacteremia or pneumonia.

Francisella tularensis

Francisella tularensis Return to Top

Francisella tularensis^[150]

1. Tularemia

Preferred regimen (1): Streptomycin 1 g IM bid
Preferred regimen (2): Gentamicin 5 mg/kg IV q24h for 10 days
Preferred regimen (3) (pregnancy): Gentamicin 5 mg/kg IV q24h for 10 days
Alternative regimen (1): Doxycycline 100 mg IV bid
Alternative regimen (2): Chloramphenicol 1 g IV q6h
Alternative regimen (3): Ciprofloxacin 400 mg IV bid until stable THEN PO for 14-21 days (total)

Helicobacter pylori

Helicobacter pylori Return to Top

1. Peptic ulcer disease^[151]

In patients aged 55 years or younger with no alarm features, two management options may be considered:
1.1 Indications for eradication therapy

In moderate to high prevalence of H. pylori infection (≥ 10%): Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test)
In low prevalence situations: Treatment indicated after the empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks

1.2 Proton pump inhibitors (PPI)

Preferred regimen (1): Lansoprazole 30 mg q12h
Preferred regimen (2): Omeprazole 20 mg q12h
Preferred regimen (3): Esomeprazole 40 mg q24h
Preferred regimen (4): Rabeprazole 20 mg q12h

1.3 Regimens for Initial Treatment

1.3.1 Triple therapy

Preferred regimen (1): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Clarithromycin 500 mg bid for 7-14 days
Preferred regimen (2): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Metronidazole 500 mg bid for 7-14 days
Preferred regimen (3) (Levofloxacin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days
Preferred regimen (4) (Rifabutin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Rifabutin 150-300 mg/day for 10 days

1.3.2 Quadruple therapy

Preferred regimen (1): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
Preferred regimen (2) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days

1.3.3 Sequential therapy

Preferred regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days

Note: Alternative triple therapies appropriate for patients with an allergy to Amoxicillin include (Proton pump inhibitor and Clarithromycin and Metronidazole) or (Proton pump inhibitor and Tetracycline and Metronidazole)

1.5 Clarithromycin resistance

1.5.1 Clarithromycin resistance ≥ 20%

Preferred regimen (1) (bismuth quadruple therapy): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
Preferred regimen (2) (sequential therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days
Preferred regimen (3) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days
Alternative regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days

1.5.2 Clarithromycin resistance < 20%

Preferred regimen (1): Proton pump inhibitor standard dose bid for 7-14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 7–14 days OR Metronidazole 250 mg qid for 7–14 days
Preferred regimen (2): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
Alternative regimen (1):Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
Alternative regimen (2): Proton pump inhibitor standard dose bid for 10 days AND Levofloxacin 500 mg bid for 10 days AND Amoxicillin 1 g bid for 10 days

Klebsiella granulomatis

Klebsiella granulomatis Return to Top

Klebsiella granulomatis (formly known as Calymmatobacterium granulomatis)

1. Granuloma inguinale (donovanosis)^[152]

Preferred regimen: Azithromycin 1 g PO once a week or 500 mg qd for 3 weeks THEN until all lesions have completely healed
Alternative regimen (1): Doxycycline 100 mg PO bid for 3 weeks THEN until all lesions have completely healed
Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks THEN until all lesions have completely healed
Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks THEN until all lesions have completely healed
Alternative regimen (4): Trimethoprim-sulfamethoxazole DS (160 mg/800 mg) tablet PO bid for at least 3 weeks THEN until all lesions have completely healed

Klebsiella pneumoniae

Klebsiella pneumoniae Return to Top

Klebsiella pneumoniae^[153]

1. Severe, nosocomial infections

1.1 Non-ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections

Preferred regimen (1): Cefepime 2 g IV q8h
Preferred regimen (2): Ceftazidime 2 g IV q8h
Preferred regimen (3): Imipenem 500 mg IV q6h
Preferred regimen (4): Meropenem 1 g IV q8h
Preferred regimen (5): Piperacillin-tazobactam 4.5 g IV q6h AND Aminoglycoside
Alternative regimen (1): Ceftriaxone 1 g IV q24h AND Metronidazole 500 mg IV q6h or 1 g IV q12h
Alternative regimen (2): Moxifloxacin 400 mg IV/PO q24h

1.2 ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections

Preferred regimen (1): Imipenem 500 mg IV q6h
Preferred regimen (2): Meropenem 1 g IV q8h
Preferred regimen (3): Ertapenem 1 g IV q24h
Preferred regimen (4): Doripenem 500 mg IV q8h
Note: In ESBLs, inconsistent activity is seen with aminoglycosides, fluoroquinolones, and piperacillin-tazobactam. Avoid cephalosporins.

Klebsiella rhinoscleromatis

Klebsiella rhinoscleromatis Return to Top

1. Rhinoscleroma^[154]^[155]^[156]

Preferred regimen (1): Ciprofloxacin 500–750 mg PO bid for 2–3 months
Preferred regimen (2): Levofloxacin 750 mg PO qd for 2–3 months
Preferred regimen (3): Trimethoprim-Sulfamethoxazole 1 DS tab PO bid for 3 months AND Rifampicin 300 mg PO bid for 3 months
Alternative regimen: Tetracycline OR Streptomycin OR Doxycycline OR Ceftriaxone OR Ofloxacin
Note (1): The optimal duration of antimicrobial therapy remains unclear. A 6-week to 6-month course of antibiotics until histology exams and cultures are negative may be required.
Note (2): Use of topical antiseptics such as Acriflavinium and Rifampin ointment has been reported with resolution of symptoms.^[157]

Legionella pneumophila

Legionella pneumophila Return to Top

1.Atypical pneumonia (Legionnaires' disease )^[158]

1.1 Mild pneumonia inpatient or outpatient, non immunocompromised

Preferred regimen (1): Azithromycin 500 mg PO qd for 3-5 days
Preferred regimen (2): Levofloxacin 500 mg PO qd for 7-10 days
Preferred regimen (3): Ciprofloxacin 500 mg PO bid for 7-10 days
Preferred regimen (4): Moxifloxacin 400 mg PO qd for 7-10 days
Preferred regimen (5): Clarithromycin 500 mg PO bid for 10-14 days
Alternative regimen (1): Doxycycline 200 mg PO loading dose, then 100 mg PO bid for 10-14 days
Alternative regimen (2): Erythromycin 500 mg PO qid for 10-14 days
Note: Patients with mild disease may be treated entirely with oral therapy.

1.2 Moderate to severe pneumonia or immunocompromised

Preferred regimen (1): Azithromycin 500 mg PO/IV q24h for 5-7 days
Preferred regimen (2): Levofloxacin 500 mg PO/IV q24h for 7-10 days OR 750 mg PO/IV q24h for 5-7 days
Alternative regimen (1): Ciprofloxacin 750 mg PO bid for 14 days
Alternative regimen (2): Moxifloxacin 400 mg PO qd for 14 days
Alternative regimen (3): Erythromycin 750-1000 mg IV q6h for 3-7 days, then 500 mg PO qid for a total course of 21 days
Alternative regimen (4): Clarithromycin 500 mg IV q12h for 3-7 days, and then 500 mg PO bid for a total course of 21 days
Note: Severely ill patients parenteral therapy is advised until improvement is seen and oral absorption is sufficient.

2 Pontiac fever

Pontiac fever is febrile, self-limited form of Legionella infection which requires only symptomatic therapy, such as analgesics for headache. Antibiotics are not indicated.

Moraxella catarrhalis

Moraxella catarrhalis Return to Top

Moraxella catarrhalis^[159]

Preferred regimen (1): TMP-SMX 1DS PO bid
Preferred regimen (2): Erythromycin 500 mg PO q6h
Preferred regimen (3): Clarithromycin 500 mg bid or XL 1 g PO qd
Preferred regimen (4): Azithromycin 500 mg single dose THEN 250 mg PO qd
Preferred regimen (5): Doxycycline 100 mg PO/IV bid
Preferred regimen (6): Parenteral cephalosporins such as Cefuroxime OR Cefotaxime OR Ceftriaxone
Preferred regimen (7): Cefprozil 200-500 mg PO bid
Preferred regimen (8): Cefpodoxime 200-400 mg PO bid
Preferred regimen (9): Cefuroxime 250-500 mg PO bid
Preferred regimen (10): Cefdinir 300 mg bid
Preferred regimen (11): Moxifloxacin 400 mg IV/PO qd
Preferred regimen (12): Levofloxacin 500 mg IV/PO qd
Preferred regimen (13): Amoxicillin-Clavulanate 875/125 mg PO bid or XL 2000/125 PO bid

Morganella morganii

Morganella morganii Return to Top

Morganella morganii^[160]

Preferred regimen (1): Imipenem 500 mg IV q6h
Preferred regimen (2): Meropenem 1.0 g IV q8h (adjust dose if necessary for renal function).
Note (1): Carbapenems are considered first line therapy due to inducible cephalosporinases, and presence of extended-spectrum beta-lactamases in some isolates
Note (2): Duration of treatment for UTI (generally complicated) is 7 days and duration of treatment for bacteremia is 14 days
Note (3): Tigecycline is not reliably effective
Alternative Regimen (1): Cefepime 2.0 g IV q8-12h
Alternative Regimen (2): Ciprofloxacin 500 mg PO/400 mg IV q12h
Alternative Regimen (3): Piperacillin 3 g IV q6h
Alternative Regimen (4): Ticarcillin 3 g IV q4h
Alternative Regimen (5): Gentamicin
Alternative Regimen (6): Tobramycin 1 mg/kg IV q24h
Alternative Regimen (7): Amikacin 3 mg/kg IV q24h
Note: Aminoglycosides can be used alone for treatment of UTI

Plesiomonas shigelloides

Plesiomonas shigelloides Return to Top

Plesiomonas shigelloides^[161]

1. Immunocompetent hosts or severe Infection

Preferred regimen: Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
Alternative regimen (1): Ofloxacin 300 mg PO bid
Alternative regimen (2): Norfloxacin 400 mg PO bid
Alternative regimen (3): TMP-SMX DS PO bid for 3 days
Alternative regimen (4): Ceftriaxone 1-2 g IV qd in severe cases

2. Immunocompromised hosts

Preferred regimen: Ciprofloxacin 500 mg PO bid for 3 days
Alternative regimen (1): Ofloxacin 300 mg PO bid
Alternative regimen (2): Norfloxacin 400 mg PO bid
Alternative regimen (3): TMP-SMX DS PO bid for 3 days if susceptible

Proteus mirabilis

Proteus mirabilis Return to Top

Proteus mirabilis^[162]

Preferred regimen (1): Ampicillin 500 mg PO q6h or 2 g IV q6h
Preferred regimen (2): Cefuroxime 250 mg PO bid or 750 mg IV q8h
Preferred regimen (3): Ciprofloxacin 250-500 mg PO bid or 400 mg IV q12h
Preferred regimen (4): Levofloxacin 500 mg PO OD or 500 mg IV q24h
Note: Duration of treatment for uncomplicated UTI 3 days, pyelonephritis 7-14 days, complicated UTI 10-21 days and bacteremia is 7-14 days

Indole positive Proteus species

Indole positive Proteus species^[163]

Preferred regimen (1): Ceftriaxone 1 g IV q24h
Preferred regimen (2): Imipenem 500 mg IV q6h
Preferred regimen (3): Ciprofloxacin 400 mg IV q12h or 250-500 mg PO bid
Preferred regimen (4): Levofloxacin 500 mg IV/PO q24h

Providencia

Providencia Return to Top

Providencia^[164]

1. Complicated uti/bacteremia/acute prostatitis

Preferred regimen (1): Ciprofloxacin 500-750 mg PO q12h or 400 mg IV q8-12h
Preferred regimen (2): Levofloxacin 500 mg IV/PO q24h
Preferred regimen (3): Piperacillin-Tazobactam 3.375 mg IV q6h
Preferred regimen (4): Ceftriaxone 1-2 g IV q24h (donot use if ESBL suspected or critically ill)
Preferred regimen (5): Meropenem 1 g IV q8h (consider if critically ill or ESBL suspected)
Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h
Preferred regimen (7): Gentamicin
Preferred regimen (8): Tobramycin acceptable if susceptible but many species are resistant
Note (1): Duration of treatment for (UTI) is 7 days common or 3-5 days after defervescence or control/elimination of complicating factors (e.g.,removal of foreign material catheter).
Note (2): Duration of treatment for (bacteremia) is 10-14 days or 3-5 days after defervescence or control/elimination of complicating factors
Note (3): Duration for acute prostatitis (2 weeks), shorter than chronic prostatitis (4-6 weeks)
Alternative regimen: TMP-SMX DS PO q12h for 10-14 days or TMP 5-10 mg/kg/day IV q6h

Pseudomonas aeruginosa

Pseudomonas aeruginosa Return to Top

Pseudomonas aeruginosa^[165]

Preferred regimen (1): Cefepime 2 g IV q8h
Preferred regimen (2): Ceftazidime 2 g IV q8h
Preferred regimen (3): Piperacillin 3-4 g IV q4h in (no benefit for pseudomonas from beta-lactamase inhibitor)
Preferred regimen (4): Ticarcillin 3-4 g IV q4h (no benefit for pseudomonas from beta-lactamase inhibitor)
Preferred regimen (5): Imipenem 500 mg—1 g IV q6h
Preferred regimen (6): Meropenem 1 g IV q8h
Preferred regimen (7): Doripenem 500 mg IV q8h
Preferred regimen (8): Ciprofloxacin 400 mg IV q8h or 750 mg PO q12h (for less serious infections)
Preferred regimen (9): Aztreonam 2 g IV q6-8h
Preferred regimen (10): Colistin 2.5 mg/kg IV q12h
Preferred regimen (11): Polymyxin B 0.75-1.25 mg/kg IV q12h
Preferred regimen (12): Gentamicin
Preferred regimen (13): Tobramycin 1.7-2.0 mg/Kg IV q8h or 5-7 mg/kg IV
Preferred regimen (14): Amikacin 2.5 mg/kg IV q12h
Note: Amikacin > Tobramycin > Gentamicin with respect to P.aeruginosa susceptibility percentages at most institutions.

Salmonella

Salmonella Return to Top

1. Salmonellosis in immunocompetent hosts^[166]

1.1 Gastroenteritis

Antimicrobial therapy is usually not recommended for uncomplicated diarrheal illness.
1.1.1 Indications for antimicrobial therapy

severedisease,
Age > 50 yrs
Prosthesis
Presence of valvular heart disease
Severe atherosclerosis
Cancer
Uremia
Immunosuppression

1.1.2 Treatment regimens

Preferred regimen (1): TMP-SMX DS PO bid for 5-7 days
Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 5-7 days
Preferred regimen (3): Ceftriaxone 2 g IV q24h for 5-7 days

1.2 Typhoid fever^[167]

1.2.1 Uncomplicated typhoid

Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg PO qd for 5–7 days)
Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg PO qd for 5–7 days)
Preferred regimen (3) (quinolone-resistant): Azithromycin 8–10 mg/kg PO qd for 7 days
Preferred regimen (4) (quinolone-resistant): Fluoroquinolone 20 mg/kg PO qd for 10-14 days
Alternative regimen (1) (fully susceptible): Chloramphenicol 50–75 mg/kg PO qd for 14-21 days
Alternative regimen (2) (fully susceptible): Amoxicillin 75–100 mg/kg PO qd for 14 days
Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) PO qd for 14 days
Alternative regimen (4) (multi drug-resistant): Azithromycin 8–10 mg/kg PO for 7 days
Alternative regimen (5) (multi drug-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
Alternative regimen (6) (quinolone-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days

1.2.2 Severe typhoid

Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg IV qd for 10-14 days)
Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg IV qd for 10-14 days)
Preferred regimen (3) (quinolone-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
Preferred regimen (4) (quinolone-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
Alternative regimen (1) (fully susceptible): Chloramphenicol 100 mg/kg PO qd for 14-21 days
Alternative regimen (2) (fully susceptible): Ampicillin 100 mg/kg PO qd for 14-21 days
Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) IV qd for 10-14 days
Alternative regimen (4) (multi drug-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
Alternative regimen (5) (multi drug-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
Alternative regimen (6) (quinolone-resistant): Fluoroquinolone 20 mg/kg IV qd for 10-14 days

1.3 Non-typhoid (serious infection)^[168]

Preferred regimen (1): 3rd generation cephalosporin (Ceftriaxone/Cefotaxime)
Preferred regimen (2): Fluoroquinolone (Ciprofloxacin, Levofloxacin)

1.4 Bacteremia^[169]

Preferred regimen (1): Ceftriaxone 2 g IV q24h

Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 7-14 days

Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 7-14 days

1.5 Vascular prosthesis infection^[170]

Preferred regimen (1): Ceftriaxone

Preferred regimen (2): Cefotaxime

Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 6 weeks

1.6 Osteomyelitis^[171]

Preferred regimen (1): Ceftriaxone 2 g IV q24h

Preferred regimen (2): Cefotaxime 2 g IV q6-8h

Preferred regimen (3): Ciprofloxacin 750 mg PO bid for ≥ 4 weeks

1.7 Arthritis^[172]

Preferred regimen (1): Ceftriaxone 2 g IV q24h

Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks

1.8 Endocarditis^[173]

Preferred regimen (1): Ceftriaxone 2 g IV q24h

Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks

1.9 UTI^[174]

Preferred regimen (1): Ceftriaxone

Preferred regimen (2): Cefotaxime

Preferred regimen (3): Ciprofloxacin IV for 1-2 weeks THEN (oral Ciprofloxacin OR TMP-SMX for 6 weeks)

1.10 Carrier state^[175]

Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 4-6 weeks
Preferred regimen (2): TMP-SMX 1DS bid PO for 6 weeks
Preferred regimen (3): Amoxicillin 500 mg PO for 6 weeks

2. Salmonellosis in immunocompromised hosts

2.1 HIV and salmonellosis^[176]

2.1.1 Gastroenteritis

Preferred regimen: Ciprofloxacin 500-750 mg PO bid or 400 mg IV q12h, if susceptible
Alternative regimen (1): Levofloxacin 750 mg PO/IV q24h
Alternative regimen (2): Moxifloxacin 400 mg PO/IV q24h
Alternative regimen (3): TMP 160 mg AND SMX 800 mg PO/IV q12h
Alternative regimen (4): Ceftriaxone 1 g IV q24h
Alternative regimen (5): Cefotaxime 1 g IV q8h
Duration of treatment for gastroenteritis without bacteremia

If CD4 count ≥ 200 cells/μL: Duration of treatment is 7–14 days
If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks

Duration of treatment for gastroenteritis with bacteremia

If CD4 count ≥ 200/μL: Duration of treatment is 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks

Note (1): Secondary prophylaxis should be considered for

Patients with recurrent Salmonella gastroenteritis with or without bacteremia
Patients with CD4 < 200 cells/μL with severe diarrhea

Serratia marcescens

Serratia marcescens Return to Top

Serratia marcescens^[177]

1. Bacteremia, pneumonia or serious infections

Preferred regimen (1): Cefepime 1-2 g IV q8h
Preferred regimen (2): Imipenem 0.5-1.0 g IV q6h
Preferred regimen (3): Ciprofloxacin 400 mg IV q8h
Alternative regimen (1): Aztreonam
Alternative regimen (2): Gentamicin
Alternative regimen (3): Amikacin
Alternative regimen (4): Piperacillin-tazobactam also often effective
Note: Duration depends on clinical response, usually 7-14 days

2. Endocarditis

Note: Choice dictated by sensitivities, 4 to 6 week duration of parenteral therapy.

3. Osteomyelitis

Note (1): Choice dictated by sensitivity profile, treat for 6-12 weeks depending upon response.
Note (2): Use IV treatment until stable/clinically improved (10-14 days Minimum) then may convert to oral therapy if appropriate.

4. UTI

Preferred regimen (1): Ciprofloxacin 250 mg PO bid or 400 mg IV q12h
Preferred regimen (2): Levofloxacin 250 mg PO qd or 500mg IV q24h
Note: Fluoroquinolones often sensitive but in seriously ill patient consider empiric coverage with two drugs (e.g.,beta-lactam and aminoglycoside or fluoroquinolones and carbapenem) until susceptibilities known.

Shigella

Shigella Return to Top

1. Shigellosis ^[178]

1.1 Adults

Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 3 days
Alternative regimen (1): Pivmecillinam 100 mg PO qid for 5 days
Alternative regimen (2): Azithromycin 1-1.5 g PO qd for 1 to 5 days

1.2 Pediatrics

Preferred regimen (1): Ciprofloxacin 15 mg/kg PO bid for 3 days
Alternative regimen (1): Pivmecillinam 20 mg/kg PO qid for 5 days
Alternative regimen (2): Ceftriaxone 50-100 mg/kg IM qd for 2 to 5 days
Alternative regimen (3): Azithromycin 6-20 mg/kg PO qd for 1 to 5 days

Stenotrophomonas maltophilia

Stenotrophomonas maltophilia Return to Top

Stenotrophomonas maltophilia^[179]

Preferred treatment: TMP-SMX 15-20 mg/kg/day (TMP component) IV/PO q8h
Alternative treatment (1): Ceftazidime 2 g IV q8h
Alternative treatment (2): Ticarcillin-clavulanate 3.1 g IV q4h
Alternative treatment (3): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
Alternative treatment (4): Ciprofloxacin 500-750 mg PO /400 mg IV q12h
Alternative treatment (5): Moxifloxacin 400 mg PO/IV
Alternative treatment (6): Levofloxacin 750 mg PO/IV .
Alternative treatment (7) (Multiply-resistantance): Colistin 2.5 mg/kg q12h IV
Note: Treatment duration uncertain, but usually ≥ 14 days

Vibrio cholerae Return to Top

1. WHO ^[180] ^[181]

Note: Antibiotic treatment for cholera patients with severe dehydration only
Adults

Preferred regimen: Doxycycline 300 mg po single dose
Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days

Pediatric

Under 12 years old

Preferred regimen: Erythromycin 12.5 mg/kg PO qid for 3 days

Over 12 years old

Preferred regimen: Doxycycline 300 mg po single dose
Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days

2. Pan American Health Organization ^[182]

Note: Antibiotic treatment for cholera patients with moderate or severe dehydration
2.1 Adult

Preferred regimen: Doxycycline 300 mg po single dose
Alternative regimen (1): Ciprofloxacin 1 g PO single dose
Alternative regimen (2): Azithromycin 1 g PO single dose

2.2 Pediatric

2.2.1 Children over 3 year, who can swallow tablets

Preferred regimen (1): Erythromycin 12.5 mg/kg/ PO qid for 3 days
Preferred regimen (2): Azithromycin 20 mg/kg PO in a single dose
Alternative regimen (1): Ciprofloxacin suspension or tablets 20 mg/kg PO single dose
Alternative regimen (2): Doxycycline suspension or tablets 2-4 mg/kg PO single dose
Note: Although doxycycline has been associated with a low risk of yellowing of the teeth in children, its benefits outweigh its risks

2.2.2 Children under 3 year, or infants who cannot swallow tablets

Preferred regimen (1): Erythromycin suspension 12.5 mg/kg/ PO qid for 3 days
Preferred regimen (2): Azithromycin suspension 20 mg/kg PO single dose
Alternative regimen (1): Ciprofloxacin suspension 20 mg/kg PO single dose
Alternative regimen (2): Doxycycline syrup 2-4 mg/kg PO single dose

2.3 Pregnancy

Preferred regimen (!): Erythromycin 500 mg/ PO qid for 3 days
Preferred regimen (2): Azithromycin 1 g PO single dose

Vibrio parahaemolyticus Return to Top

Vibrio parahaemolyticus ^[183]

1. Mild to Moderate

Treatment is not necessary in most cases of V. parahaemolyticus infection
There is no evidence that antibiotic treatment decreases the severity or the length of the illness
Patients should drink plenty of liquids to replace fluids lost through diarrhea

2. Severe or prolonged illnesses

Preferred regimen: Tetracycline OR Ciprofloxacin

Vibrio vulnificus Return to Top

Vibrio vulnificus ^[184]

Note: If V. vulnificus is suspected, treatment should be initiated immediately because antibiotics improve survival
Preferred regimen: Doxycycline 100 mg PO/IV bid for 7-14 days AND Ceftazidime 1-2 g IV/IM q8h
Note: A single agent regimen with a fluoroquinolone such as Levofloxacin, Ciprofloxacin or Gatifloxacin, has been reported to be at least as effective in an animal model as combination drug regimens with Doxycycline and a Cephalosporin
Pediatric regimen: Doxycycline AND Fluoroquinolones; trimethoprim-sulfamethoxazole AND an Aminoglycoside

Bacteria – Atypical Organisms

Chlamydophila pneumoniae

Chlamydophila pneumoniae Return to Top

1. Atypical pneumonia ^[185]

1.1 Adult

Preferred regimen (1): Doxycycline 100 mg PO bid for 14-21 days
Preferred regimen (2): Tetracycline 250 mg PO qid for 14-21 days
Preferred regimen (3): Azithromycin 500 mg PO as a single dose, followed by 250 mg PO qd for 4 days
Preferred regimen (4): Clarithromycin 500 mg PO bid for 10 days
Preferred regimen (5): Levofloxacin 500 mg IV OR PO qd for 7 to 14 days
Preferred regimen (6): Moxifloxacin 400 mg PO qd for 10 days.

1.2 Pediatric

Preferred regimen (1): Erythromycin suspension PO 50 mg/kg/day for 10 to 14 days
Preferred regimen (2): Clarithromycin suspension PO 15 mg/kg/day for 10 days
Preferred regimen (3): Azithromycin suspension PO 10 mg/kg once on the first day, followed by 5 mg/kg qd daily for 4 days

2. Upper respiratory tract infection^[186]

2.1 Bronchitis

Antibiotic therapy for C. pneumoniae is not required.

2.2 Pharyngitis

Antibiotic therapy for C. pneumoniae is not required.

2.3 Sinusitis

Antibiotic therapy is advisable if symptoms remain beyond 7-10 days.

Chlamydia trachomatis

Chlamydia trachomatis Return to Top

1 Chlaymydial infections ^[187]

1.1 Chlamydial Infections in Adolescents and Adults

Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
Preferred regimen (2): Azithromycin 1 g PO in a single dose
Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
Note: Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient's symptoms or chlamydia diagnosis.

1.2 Chlamydial Infections in patients with HIV Infection

Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
Preferred regimen (2): Azithromycin 1 g PO in a single dose
Preferred regimen (3): Azithromycin 1 g PO in a single dose
Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.

1.3 Pregancy

Preferred regimen: Azithromycin 1 g PO in a single dose
Alternative regimen (1): Amoxicillin 500 mg PO tid for 7 days
Alternative regimen (2): Erythromycin base 500 mg PO qid for 7 days
Alternative regimen (3): Erythromycin base 250 mg PO qid for 14 days
Alternative regimen (4): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
Alternative regimen (5): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
Note:Doxycycline, Ofloxacin, and Levofloxacin are contraindicated in pregnant women

1.4 Management of sex partners

Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
Preferred regimen (2): Azithromycin 1 g PO in a single dose
Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or Chlamydia diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present

2. Chlamydial infection among neonates

2.1 Ophthalmia Neonatorumcaused by C. trachomatis

Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days
Note: The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated.

2.2 Infant Pneumonia

Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days

3.Chlamydial infection among infants and childern

3.1 Infants and childern who weigh < 45 kg

Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days

3.2 Infants and childern who weigh ≥45 kg but who are aged <8 years

Preferred regimen: Azithromycin 1 g PO in a single dose

3.3 Infants and childern aged ≥8 years

Preferred regimen (1): Azithromycin 1 g PO in a single dose
Preferred regimen (2): Doxycycline 100 mg PO bid for 7 days

4. Lymphogranuloma venereum (LGV) ^[188]

Preferred regimen: Doxycycline 100 mg PO bid for 21 days
Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
Note (1): Azithromycin 1 g PO once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required.
Note (2): Pregnant and lactating women should be treated with Erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.
Note (3): Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.
Note (4): Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be examined and tested for urethral, cervical, or rectal chlamydial infection depending on anatomic site of exposure. They should be presumptively treated with a chlamydia regimen ( Azithromycin 1 g PO single dose OR Doxycycline 100 mg PO bid for 7 days).

Chlamydophila psittaci

Chlamydophila psittaci Return to Top

1. Respiratory psittacosis (Pneumonia)^[189]

1.1 Adult

Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
Preferred regimen (2): Tetracycline 500 mg PO qid for 10-21 days
Alternative regimen: Minocycline

1.2 Pediatric

1.2.1 Mild infection, Infants >3 months

Preferred regimen: Azithromycin 10 mg/kg PO qd on day 1 THEN 5 mg/kg PO q24h for 4 days; (Maximum, 500 mg for 1st dose, 250 mg for subsequent doses)

1.2.2 Moderate-severe infection, Infants >3 months

Preferred regimen: Azithromycin 10 mg/kg IV q24h for 2 days THEN 5 mg/kg PO qd for 3 days; (Maximum, 500 mg/dose IV; 250 mg/dose PO)

1.3 Pregnant Patients

Preferred regimen: Azithromycin 500 mg PO on day 1 THEN by 250 mg qd on days 2-5 OR 500 mg IV as a single dose for at least 2 days, followed by 500 mg PO qd for 7- 10 days

Coxiella burnetii

Coxiella burnetii Return to Top

1. Acute Q fever ^[190]

1.1 Adults

Preferred Regimen: Doxycycline 100 mg PO bid for 14 days

1.2 Pediatric

1.2.1 ≥ 8 years old

Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)

1.2.2 < 8 years old with high risk criteria

Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)

1.2.3 < 8 years old with mild or uncomplicated illness

Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 5 days (Maximum, 100 mg per dose)
Alternative regimen: (If patient remains febrile past 5 days of treatment) Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (Maximum, 800 mg per dose)

1.3 Pregnant women

Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO bid
Note: Should be given throughout pregnancy

2. Chronic Q fever

2.1 Endocarditis or vascular infection

Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for ≥18 months
Note: Childern and pregnant women consultation recommended

2.2 Non-cardiac organ disease

Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid
Note: childern and pregnant women consultation recommended

2.3 Postpartumwith serologic profile for chronic Q fever

Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for 12 months
Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024); Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
Note (2): Post-Q fever fatigue syndrome- no current recommendation

Mycoplasma pneumoniae

Mycoplasma pneumoniae Return to Top

1. Atypical pneumonia^[191]^[192]

Preferred regimen (1): Azithromycin 500 mg PO qd on day 1 and 250 mg PO qd on days 2 to 5
Preferred regimen (2): Clarithromycin 500 mg PO qd for 14 days
Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
Preferred regimen (4): Levofloxacin 750 mg PO qd for 14 days
Alternative regimen : Doxycycline 100 mg PO bid for 14 days

Mycoplasma genitalium

Mycoplasma genitalium Return to Top

1. Urethritis and cervicitis^[193]

Preferred regimen (macrolide-susceptible strains) (1): Azithromycin 1 g PO as a single dose
Preferred regimen (macrolide-susceptible strains) (2): Azithromycin 500 mg PO as a dose followed by 250 mg PO qd for 4 days
Preferred regimen (for patients with previous treatment failures): Moxifloxacin 400 mg PO qd for 7–14 days

2. Pelvic inflammatory disease (PID)^[194]

Preferred regimen: Moxifloxacin 400 mg PO qd for 14 days

3. Specific considerations^[195]

3.1 Management of sex partners
Sex partners should be managed according to guidelines for patients with nongonococcal urethritis, cervicitis, and pelvic inflammatory disease.
3.2 HIV infection
Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative.

Bacteria – Miscellaneous

Gardnerella vaginalis Return to Top

1.Bacterial Vaginosis^[196]

Gardnerella vaginalis is one of the anaerobic bacteria causing Bacterial Vaginosis,which is a polymicrobial clinical syndrome

Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
Preferred regimen (3): Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
Alternative regimen (1): Tinidazole 2 g PO qd for 2 days
Alternative regimen (2): Tinidazole 1 g PO qd for 5 days
Alternative regimen (3): Clindamycin 300 mg PO bid for 7 days
Alternative regimen (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
Note: Clindamycin ovules use an oleaginous base that might weaken latex or rubber products (e.g., condoms and vaginal contraceptive diaphragms). Use of such products within 72 hours following treatment with clindamycin ovules is not recommended.

2. Management of Sex Partners

Routine treatment of sex partners is not recommended.

3. Special Considerations

3.1 Allergy, Intolerance, or Adverse Reactions
Intravaginal Clindamycin cream is preferred in case of allergy or intolerance to Metronidazole or Tinidazole. Intravaginal Metronidazole gel can be considered for women who are not allergic to Metronidazole but do not tolerate oral metronidazole. It is advised to avoid consuming alcohol during treatment with nitroimidazoles. To reduce the possibility of a disulfiram-like reaction, abstinence from alcohol use should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.

3.2 Pregnancy

Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
Note: Tinidazole should be avoided during pregnancy

3.3 HIV Infection

Women with HIV who have BV should receive the same treatment regimen as those who do not have HIV infection.

Eikenella corrodens Return to Top
Bordetella pertussis Return to Top
Bartonella Return to Top
Stenotrophomonas maltophilia Return to Top
Acinetobacter baumannii Return to Top

Bacteria – Anaerobic Gram-Negative Bacilli

Bacteroides fragilis Return to Top

Bacteroides fragilis ^[197]

1. Monotherapy

Preferred regimen (1): Imipenem

Preferred regimen (2): Ertapenem

Preferred regimen (3): Meropenem

Preferred regimen (4): Doripenem 0.5-1.0 g IV q6h

Preferred regimen (5): Piperacillin-tazobactam 3.375 g IV q6h

Preferred regimen (6): Ampicillin-sulbactam 1-2 g IV q6h

Preferred regimen (7): Tigecycline 100 mg IV THEN 50 mg IV q12h

2. Combination therapy

Preferred regimen: Metronidazole 0.75-1.0 g IV q12h AND Cefotaxime 1.5-2 g IV q6h OR Aztreonam 1-2 g IV q8h OR Ceftriaxone 1 g IV q12h

Fusobacterium necrophorum Return to Top

Fungi

Aspergillosis Return to Top
^[198]
1. Invasive pulmonary aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

2. Invasive sinus aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

3. Tracheobronchial aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

4. Chronic necrotizing pulmonary aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

5. Aspergillosis of the CNS

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

Note: There are drug interactions with anticonvulsant therapy.

6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.

7. Aspergillus osteomyelitis and septic arthritis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
Note: Surgical resection of devitalized bone and cartilage is important for curative intent.

8. Aspergillus infections of the eye (endophthalmitis and keratitis)

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.

9. Cutaneous aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
Note: Surgical resection is indicated when feasible.

10. Aspergillus peritonitis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

11. Prophylaxis against invasive aspergillosis

Preferred regimen: Posaconazole PO 200 mg tid
Alternative regimen: (1) Itraconazole 200 mg IV bid for 2 days then 200 mg IV qd OR Itraconazole PO 200mg bid
Alternative regimen: (2) Micafungin 50 mg/day PO qd

12. Aspergilloma

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd

13. Chronic cavitary pulmonary aspergillosis

Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (6): Micafungin 100–150 mg/day PO qd^[199]^[198]
Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.

Note: long-term therapy might be needed.

14. Allergic bronchopulmonary Itraconazole aspergillosis

Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Alternative regimen (1): Voriconazole PO 200 mg bid
Alternative regimen (2): Posaconazole PO 400 mg bid
Note: Corticosteroids are a cornerstone of the therapy.

15. Allergic aspergillus sinusitis

Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
Note: Few data available for other agents.

16. Relative indications for surgical treatment of invasive aspergillosis

Pulmonary lesion in proximity to great vessels or pericardium;
Pericardial infection;
Invasion of chest wall from contiguous pulmonary lesion;
Aspergillus empyema;
Persistent hemoptysis from a single cavitary lesion;
Infection of skin and soft tissues;
Infected vascular catheters and prosthetic devices;
Endocarditis;
Osteomyelitis;
Sinusitis;
Cerebral lesions.

Blastomycosis Return to Top
Blastomycosis^[200]

1. Mild to moderate pulmonary blastomycosis

Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
Note: Oral Itraconazole, 200 mg tid PO for 3 days and THEN 200 mg PO qd or bid for 6–12 months

2. Moderately severe to severe pulmonary blastomycosis

Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
Note: Oral Itraconazole, 200 mg tid PO for 3 days THEN 200 mg PO bid, for a total of 6–12 months

3. Mild to moderate disseminated blastomycosis

Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
Note (1): Treat osteoarticular disease for 12 months
Note (2): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months

4. Moderately severe to severe disseminated blastomycosis

Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
Note: oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months

5. CNS disease

Preferred regimen: Lipid Amphotericin B 5 mg/kg IV qd for 4–6 weeks AND an oral azole for at least 1 year
Note (1): Step-down therapy can be with Fluconazole, 800 mg/day PO qd or bid OR Itraconazole, 200 mg bid or tid OR voriconazole, 200–400 mg bid.
Note (2): Longer treatment may be required for immunosuppressed patients.

6. Immunosuppressed patients

Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
Preferred regimen (2): Amphotericin B deoxycholate, 0.7–1 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
Note (1): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 12 months
Note (2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.

7. Pregnant women

Preferred regimen: Lipid Amphotericin B 3–5 mg/kg IV qd
Note (1): Azoles should be avoided because of possible teratogenicity
Note (2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg IV qd

8. Children with mild to moderate disease

Preferred regimen: Itraconazole 10 mg/kg PO qd for 6–12 months
Note: Maximum dose 400 mg/day

9. Children with moderately severe to severe disease

Preferred regimen (1): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
Preferred regimen (2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
Note: Children tolerate Amphotericin B deoxycholate better than adults do.

Paracoccidioidomycosis Return to Top

Preferred regimen (1): ^[201]

Adults: Itraconazole 200 mg/day PO
Children: Itraconazole (<30/kg and >5 yr) 5-10 mg/kg/day PO
Note: Treatment duration based on organ involvement:

Mild involvement: 6-9 months
Moderate involvement: 12-18 months

Preferred regimen (2): ^[201]

Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV bid
Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV, bid
Note (1): Treatment duration based on organ involvement:

Minor involvement: 12 months
Moderate involvement: 18-24 months

Note (2): Preferred treatment in children due to larger experience.
Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV tid until patient condition improves so that oral medication can be given.

Preferred regimen (3): Amphotericin B deoxycholate 1 mg/kg/day IV until patient improves and can be treated by the oral route.^[201]

Note: Preferred in severe forms of the disease.^[201]

Alternative regimen (4): Ketoconazole 200-400 mg/day PO for 9-12 months^[202]
Alternative regimen (5): Voriconazole initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months^[203]

Note: Diminish the dose to 50% if weight is <40 kg.

Candidiasis Return to Top
:*1. Candidemia^[204]

1.1. Nonneutropenic adults

Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
Preferred regimen (3): Micafungin 100 mg daily
Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
Alternative regimen (3): Voriconazole 400 mg (6 mg/kg) PO/IV bid for 2 doses, THEN 200 mg (3 mg/kg) bid
Note (1): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
Note (2): Choose an echinocandin for moderately severe to severe illness and for patients with recent azole exposure.
Note (3): Treat for 14 days after first negative blood culture result and resolution of signs and symptoms associated with candidemia.
Note (4): Ophthalmological examination recommended for all patients.

1.2. Neutropenic patients

Preferred regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily
Preferred regimen (2): Micafungin 100 mg daily
Preferred regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily
Preferred regimen (4): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
Alternative regimen (2): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
Note: Fluconazole is recommended for patients without recent azole exposure and who are not critically ill.

2. Suspected candidiasis treated with empiric antifungal therapy^[204]

2.1. Nonneutropenic patients

Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
Preferred regimen (3): Micafungin 100 mg daily
Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
Note (1): Duration of therapy is uncertain, but should be discontinued if cultures and/or serodiagnostic tests have negative results.
Note (2): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
Note (3): Echinocandin is preferred for patients with recent azole exposure, patients with moderately severe to severe illness, or patients who are at high risk of infection due to C. glabrata or C. krusei.
Note (4): Empirical antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites

2.2. Neutropenic patients

Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
Preferred regimen (3): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
Alternative regimen (2): Itraconazole 200 mg (3 mg/ kg) bid
Note (1): In most neutropenic patients, it is appropriate to initiate empiric antifungal therapy after 4 days of persistent fever despite antibiotics.
Note (2): Do not use an azole in patients with prior azole prophylaxis.

3. Urinary tract infection^[204]

3.1. Asymptomatic cystitis

Preferred regimen: Therapy not usually indicated, unless patients are at high risk (e.g., neonates and neutropenic adults) or undergoing urologic procedures.
Note (1): Elimination of predisposing factors recommended
Note (2): For high-risk patients, treat as for disseminated candidiasis
Note (3): For patients undergoing urologic procedures, fluconazole, 200–400 mg (3–6 mg/kg) daily or Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg daily for several days before and after the procedure.

3.2. Symptomatic cystitis

Preferred regimen: Fluconazole 200 mg (3 mg/kg) daily for 2 weeks
Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg for 1–7 days
Alternative regimen (2): Flucytosine 25 mg/kg qid for 7–10 days
Note: Amphotericin B deoxycholate(AmB-d) bladder irrigation is recommended only for patients with refractory fluconazole-resistant organisms (e.g., Candida krusei and Candida glabrata).

3.3 Pyelonephritis

Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks
Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
Alternative regimen (2): Flucytosine (5-FC) 25 mg/kg qid for 2 weeks
Note: For patients with pyelonephritis and suspected disseminated candidiasis, treat as for candidemia.

4. Urinary fungus balls^[204]

Preferred regimen (1): Surgical removal strongly recommended
Preferred regimen (2): Fluconazole 200–400 mg (3–6 mg/kg) daily
Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
Note (1): Local irrigation with Amphotericin B deoxycholate(AmB-d) may be a useful adjunct to systemic antifungal therapy.
Note (2): Treatment duration should be until symptoms have resolved and urine cultures no longer yield Candida species.

5. Vulvovaginal candidiasis^[204]

Preferred regimen (1): Butoconazole 2% cream 5 g intravaginally for 3 days
Preferred regimen (2): Butoconazole 2% cream 5 g (butoconazole1-sustained release), single intravaginal application
Preferred regimen (3): Clotrimazole 1% cream 5 g intravaginally for 7–14 days
Preferred regimen (4): Clotrimazole 100-mg vaginal tablet for 7 days
Preferred regimen (5): Clotrimazole 100-mg vaginal tablet, 2 tablets for 3 days
Preferred regimen (6): Miconazole 2% cream 5 g intravaginally for 7 days
Preferred regimen (7): Miconazole 100-mg vaginal suppository, 1 suppository for 7 days
Preferred regimen (8): Miconazole 200-mg vaginal suppository, 1 suppository for 3 days
Preferred regimen (9): Miconazole 1200-mg vaginal suppository, 1 suppository for 1 day
Preferred regimen (10): Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
Preferred regimen (11): Tioconazole 6.5% ointment 5 g intravaginally in a single application
Preferred regimen (12): Terconazole 0.4% cream 5 g intravaginally for 7 days
Preferred regimen (13): Terconazole 0.4% cream 5 g intravaginally for 3 days
Preferred regimen (14): Terconazole 80-mg vaginal suppository, 1 suppository for 3 days
Preferred regimen (15): Fluconazole 150 mg single dose for uncomplicated vaginitis
Note: For recurring Candida Vulvovaginal candidiasis (VVC), 10–14 days of induction therapy with a topical or oral azole, followed by fluconazole at a dosage of 150 mg once per week for 6 months, is recommended

6. Chronic disseminated candidiasis^[204]

Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for stable patients
Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for severely ill patients
Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily for severely ill patients
Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily, followed by oral Fluconazole when clinically appropriate
Alternative regimen (2): Micafungin 100 mg daily, followed by oral Fluconazole when clinically appropriate
Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily, followed by oral Fluconazole when clinically appropriate
Note (1): Transition from Lipid formulation of amphotericin B(LFAmB) or Amphotericin B deoxycholate(AmB-d) to fluconazole is favored after several weeks in stable patients.
Note (2): Duration of therapy is until lesions have resolved (usually months) and should continue through periods of immunosuppression (e.g., chemotherapy and transplantation).
Note (3): Therapy should be continued for weeks to months, until calcification occurs or lesions resolve.

7. Candida osteoarticular infection^[204]

7.1. Osteomyelitis

Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for 6–12 months
Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for at least 2 weeks, then Fluconazole 400 mg daily for 6–12 months
Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
Alternative regimen (4): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
Note (1): Duration of therapy usually is prolonged (6–12 months)
Note (2): Surgical debridement is frequently necessary

7.2. Septic arthritis

Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) for at least 6 weeks
Preferred regimen (2): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
Note (1): Duration of therapy usually is for at least 6 weeks, but few data are available.
Note (2): Surgical debridement is recommended for all cases.
Note (3): For infected prosthetic joints, removal is recommended for most cases.

8. CNS candidiasis^[204]

Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid for several weeks followed by Fluconazole 400–800 mg (6–12 mg/kg) daily
Alternative regimen (1): Fluconazole 400–800 mg (6–12 mg/ kg) daily for patients unable to tolerate Lipid formulation of amphotericin B (LFAmB)
Note (1): Treat until all signs and symptoms, CSF abnormalities, and radiologic abnormalities have resolved.
Note (2): Removal of intraventricular devices is recommended.

9. Candida endophthalmitis^[204]

Preferred regimen (1): Amphotericin B deoxycholate(AmB-d) 0.7–1 mg/kg AND Flucytosine 25 mg/ kg qid
Preferred regimen (2): Fluconazole 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily
Alternative regimen (2): Voriconazole 6 mg/kg q12h for 2 doses, then 3–4 mg/kg q12h
Alternative regimen (3): Caspofungin 70 mg loading dose, THEN 50 mg daily
Alternative regimen (4): Micafungin 100 mg daily
Alternative regimen (5): Anidulafungin 200 mg loading dose, THEN 100 mg daily
Note (1): Alternative therapy is recommended for patients intolerant of or experiencing failure of Amphotericin B and Flucytosine therapy
Note (2): Duration of therapy is at least 4–6 weeks as determined by repeated examinations to verify resolution.
Note (3): Diagnostic vitreal aspiration should be done if etiology unknown.
Note (4): Fluconazole at a dosage of 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
Note (5): Surgical intervention for patients with severe endophthalmitis or vitreitis

10. Candida infection of the cardiovascular system^[204]

10.1. Endocarditis

Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
Preferred regimen (2): Amphotericin B deoxycholate AmB-d 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
Preferred regimen (3): Caspofungin 50–150 mg daily
Preferred regimen (4): Micafungin 100–150 mg daily
Preferred regimen (5): Anidulafungin 100–200 mg daily
Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
Note (1): Valve replacement is strongly recommended.
Note (2): For those who are unable to undergo surgical removal of the valve, chronic suppression with fluconazole 400–800 mg (6–12 mg/kg) daily is recommended.
Note (3): Lifelong suppressive therapy for prosthetic valve endocarditis if valve cannot be replaced is recommended.

10.2. Pericarditis or myocarditis

Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
Preferred regimen (3): Caspofungin 50–150 mg daily
Preferred regimen (4): Micafungin 100–150 mg daily
Preferred regimen (5): Anidulafungin 100–200 mg daily
Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
Note(1): Therapy is often for several months, but few data are available
Note(2): A pericardial window or pericardiectomy is recommended.

10.3. Suppurative thrombophlebitis

Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
Preferred regimen (3): Caspofungin 50–150 mg daily
Preferred regimen (4): Micafungin 100–150 mg daily
Preferred regimen (5): Anidulafungin 100–200 mg daily
Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
Note(1): Surgical incision and drainage or resection of the vein is recommended if feasible.
Note(2): Treat for at least 2 weeks after candidemia has cleared.

10.4. Infected pacemaker, ICD, or VAD

Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
Preferred regimen (2): Amphotericin B deoxycholate (AmB-d) 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
Preferred regimen (3): Caspofungin 50–150 mg daily
Preferred regimen (4): Micafungin 100–150 mg daily
Preferred regimen (5): Anidulafungin 100–200 mg daily
Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
Note(1): Removal of pacemakers and ICDs strongly recommended.
Note(2): Treat for 4–6 weeks after the device removed.
Note(3): For VAD that cannot be removed, chronic suppressive therapy with fluconazole is recommended.

11. Neonatal candidiasis^[204]

Preferred regimen (1): Amphotericin B deoxycholate (AmB-d) 1 mg/kg daily for 3 weeks
Preferred regimen (2): Fluconazole 12 mg/kg daily for 3 weeks
Alternative regimen (1): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for 3 weeks
Note (1): A lumbar puncture and dilated retinal examination should be performed on all neonates with suspected invasive candidiasis.
Note (2): Intravascular catheter removal is strongly recommended.
Note (3): Duration of therapy is at least 3 weeks.
Note (4): Lipid formulation of amphotericin B (LFAmB) used only if there is no renal involvement.
Note (5): Echinocandins should be used with caution when other agents cannot be used.

12. Candida isolated from respiratory secretions^[204]

Preferred regimen (1): Therapy not recommended
Note (1): Candida lower respiratory tract infection is rare and requires histopathologic evidence to confirm a diagnosis.

13. Nongenital mucocutaneous candidiasis^[204]

13.1. Oropharyngeal

Preferred regimen (1): Clotrimazole troches 10 mg 5 times daily
Preferred regimen (2): Nystatin suspension at a concentration of 100,000 U/mL and a dosage of 4–6 mL qid OR 1–2 Nystatin pastilles (200,000 U each) administered qid for 7–14 days
Preferred regimen (3): Fluconazole 100–200 mg PO (3 mg/kg) daily for 7–14 days
Alternative regimen (1): Itraconazole solution 200 mg daily
Alternative regimen (2): Posaconazole suspension at a dosage of 400 mg twice daily for 3 days, THEN 400 mg daily for up to 28 days
Alternative regimen (3): Voriconazole 200 mg bid
Alternative regimen (4): Amphotericin B deoxycholate (AmB-d) 1-mL oral suspension administered at a dosage of 100 mg/mL qid
Alternative regimen (5): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
Alternative regimen (6): Micafungin 100 mg IV daily
Alternative regimen (7): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
Alternative regimen (8): Amphotericin B deoxycholate (AmB-d) 0.3 mg/kg daily
Note(1): Fluconazole is recommended for moderate-to-severe disease, and topical therapy with clotrimazole or nystatin is recommended for mild disease.
Note(2): Treat uncomplicated disease for 7–14 days.
Note(3): For refractory disease, itraconazole, voriconazole, posaconazole, or AmB suspension is recommended.

13.2. Esophageal

Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) PO daily
Preferred regimen (2): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
Preferred regimen (3): Micafungin 100 mg IV daily
Preferred regimen (4): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
Preferred regimen (4): AmB-d 0.3–0.7 mg/kg daily
Alternative regimen (1): Itraconazole oral solution 200 mg daily
Alternative regimen (2): Posaconazole 400 mg bid
Alternative regimen (3): Voriconazole 200 mg bid
Note(1): Oral fluconazole is preferred.
Note(2): For patients unable to tolerate an oral agent, IV fluconazole, an echinocandin, or AmB-d is appropriate.
Note(3): Treat for 14–21 days.
Note(4): For patients with refractory disease, the alternative therapy as listed or AmB-d or an echinocandin is recommended.

Chromoblastomycosis Return to Top
^[205]

Preferred regimen: Itraconazole 200-400 mg PO q24h OR 400 mg pulse therapy once daily for 1 week monthly for 6-12 months
Note: Pulse therapy reduces cost but it is questionable if it produces resistance to the drug.
Alternative regimen (1): Terbinafine 500-1000 mg PO qd for 6-12 months
Alternative regimen (2): Posaconazole 800 mg PO qd for 6-12 months
Alternative regimen (3): 5-fluorocytosine 100-150 mg/kg/day PO qd for 6-12 months
Note: This disease has a low cure ratio and high relapse ratio. Physical treatment is needed to achieve better results:

Cryosurgery with liquid nitrogen - most used physical therapy, it's used in localized lesions and it has a very good treatment response, probably achieved by immune mechanisms since fungi are eliminated from lesions as late as 1-2 weeks after the therapy.
Thermotherapy - used in conjunction with systemic therapy, was developed by Japanese authors and consists in placing "pocket warmers" in the lesions for 24h/day for some months, as the fungi is sensible to heat.
Laser vaporization - studied in Germany as an alternative therapy, reported to successfully treat relapsing lesions.

Coccidioidomycosis Return to Top

1. Primary pulmonary infection ^[206]

1.1 Indications for antifungal therapy

Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
Diabetes
Preexisting cardiomyopathy
Pregnancy (third trimester)
Filipino or African
Weight loss of > 10%
Intense night sweats persisting longer than 3 weeks
Infiltrates involving more than one-half of one lung or portions of both lungs
Prominent or persistent hilar adenopathy
Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16

1.2 Patients with low risk of complications or dissemination

For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.

1.3 Patients with high risk of complications or dissemination

1.3.1 Mild to moderate pneumonia

Preferred regimen (1): Itraconazole solution 200 mg PO bid or IV q12h
Preferred regimen (2): Fluconazole 400 mg PO q24h for 3–12 months

1.3.2 Locally severe or disseminated pneumonia

Preferred regimen: (Amphotericin B 0.6–1 mg/kg PO qd every 7 days THEN 0.8 mg/kg PO every other day OR Liposomal Amphotericin B 3-5 mg/kg IV q24 hrs OR Amphotericin B lipid complex 5 mg/kg IV q24 hrs until clinical improvement) followed by Itraconazole OR Fluconazole for at least 1 year.
Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
Note (2): Consultation with specialist recommendation, surgery may be required.

2. Meningitis

2.1 Adult

Preferred regimen: Fluconazole 400–1,000 mg PO q24h indefinitely.
Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg qd intrathecal (intraventricular) via reservoir device OR Itraconazole 400–800 mg q24h OR Voriconazole
Note: Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.

2.2 Child

Preferred regimen: Fluconazole PO (Pediatric dose not established, 6 mg per kg q24h used)
Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device OR itra 400–800 mg q24h OR Voriconazole

3. Special considerations for HIV/AIDS patients^[207]

3.1 Clinically mild infections (e.g., focal pneumonia)

Preferred regimen: Fluconazole 400 mg PO daily OR Itraconazole 200 mg PO bid
Alternative regimen (unresponsive to Fluconazole or Itraconazole): Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional

3.2 Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)

3.2.1 Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV q12hrs OR Lipid formulation Amphotericin B 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
3.2.2 Alternative regimen: Some specialists will add a triazole (Fluconazole or Itraconazole, with Itraconazole (preferred for bone disease) 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped
Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL

3.3 Meningeal Infections

Preferred regimen: Fluconazole 400–800 mg IV or PO daily
Alternative regimen: Itraconazole 200 mg PO tid for 3 days THEN 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid OR Intrathecal Amphotericin B deoxycholate when triazole antifungals are ineffective.
Note (1): Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.
Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy

3.4 Chronic Suppressive Therapy

Preferred regimen (1): Fluconazole 400 mg PO qd
Preferred regimen (2): Itraconazole 200 mg PO bid
Alternative regimen (1): Posaconazole 200 mg PO bid
Alternative regimen (2): Voriconazole 200 mg PO bid

Cryptococcosis Return to Top
Cryptococcus Return to Top

1. Cryptococcus neoformans

1.1 Cryptococcus neoformans meningitis in HIV infected patients^[208]

Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks.
Alternative regimen for induction and consolidation (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd OR Liposomal AmB 3-4 mg/kg IV qd OR AmB lipid complex 5mg/kg IV qd for 4-6 weeks
Alternative regimen for induction and consolidation (2): Amphotericin B deoxycholate 0.7 mg/kg IV qd PLUS Fluconazole 800mg PO qd for 2 weeks, followed by Fluconazole 800mg PO qd for at least 8 weeks
Alternative regimen for induction and consolidation (3): Fluconazole (>800 mg PO qd, 1200mg PO qd is favored) PLUS Flucytosine (100mg/kg/day PO qid) for 6 weeks
Alternative regimen for induction and consolidation (4): Fluconazole PO 800-2000mg qd for 10-12 weeks
Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy AND Fluconazole 200mg PO qd
Alternative regimen for maintenance and prophylactic therapy: Itraconazole 200mg PO bid - monitor drug-level OR Amphotericin B deoxycholate (1 mg/kg) per week IV (should be used in azole-intolerant patients).
Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
Note (2): Do not use acetazolamide OR mannitol OR corticosteroids to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).

1.2. Cerebral cryptococcomas

Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks
Note: Consider surgery if lesions are larger than 3cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.

1.3. Cryptococcus neoformans meningitis in HIV negative patients

Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by Fluconazole 400mg PO qd for 8 weeks. If there's toxicity to AmBd, consider changing to LFAmB in the second 2 weeks.
Note (1): After induction and consolidation therapy, start Fluconazole 200mg (3mg/kg) PO qd for 6-12 months.
Note (2): If Flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks.

1.4. Cryptococcus neoformans pulmonary disease - immunosupressed

Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:

Preferred regimen: Fluconazole 400mg PO qd for 6-12 months

Severe pneumonia or disseminated disease or CNS infection:

Preferred regimen: treat like CNS cryptococcosis.

Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS.

1.5 Cryptococcus neoformans pulmonary disease - non-immunosupressed

Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:

Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
Alternative regimen: if Fluconazole is unavailable or contraindicated, Itraconazole 200mg PO bid, Voriconazole 200 mg PO bid, and Posaconazole 400mg PO bid

If there's severe pneumonia, disseminated disease or CNS infection:

Preferred regimen: treat like CNS cryptococcosis for 6-12 months.

1.6 Cryptococcus neoformans non-lung, non-CNS infection

Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):

Preferred regimen: treat like CNS infection.

If infection occurs at a single site and no immunosupressive risk factors

Preferred regimen: Fluconazole 400mg PO qd for 6-12 months

1.7. Cryptococcosis in Children

Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV PLUS Flucytosine 100mg/kg PO or IV qid for 2 weeks followed by Fluconazole 10-12mg/kg PO qd for 8 weeks
Alternative regimen: patients with renal dysfunction: change Amphotericin B deoxycholate by Liposomal AmB 5mg/kg IV qd or Amphotericin B lipid complex (ABLC) 5mg/kg IV qd
Preferred regimen for maintenance: Fluconazole 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.

Cryptococcal pneumonia:

Preferred regimen Fluconazole 6-12mg/kg PO qd for 6-12 months

1.8. Cryptococcosis in Pregnant Women

Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd. Consider using Flucytosine in relationship to benefit risk basis, since it is a Category C drug for pregnancy. Start Fluconazole after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
Note: If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.

2. Cryptococcus gatti

Disseminated cryptococcosis or CNS disease:

Preferred regimen: treatment is the same as C. neoformans.

Pulmonary disease: single and small cryptococcoma:

Preferred regimen: Fluconazole 400mg per day PO for 6-18months

Pulmonary disease: Very large or multiple cryptococcomas:

Preferred regimen: administer Flucytosine AND AmB deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months.
Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy

Tinea cruris Return to Top

Tinea Cruris^[209]

Preferred regimen: Interdigital: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole, clotrimazole), Griseofulvin 250mg tid PO for 14 days should be used in resistant to topic therapy cases.

Tinea corporis Return to Top

Tinea Corporis

2.1 Small, well-defined lesions:

Preferred regimen: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole, clotrimazole).

2.2 Larger lesions:

Preferred regimen: Larger lesions: terbinafine PO 250mg/day for 2 weeks; itraconazole PO 200mg/day for 1 week, fluconazole PO 250mg weekly for 2-4 weeks.

Tinea pedis Return to Top

1. Tinea Pedis

Preferred regimen: Interdigital: Topical cream/ointment: terbinafine, imidazoles (miconazole, econazole, clotrimazole), undecenoic acid, tolnaftate.
Note (1): If "Dry type": Oral: terbinafine PO 250mg/day for 2-4 weeks, itraconazole PO 400mg/day for 1 week per month (repeat if necessary), fluconazole PO 200mg weekly for 4-8 weeks.

Tinea capitis Return to Top

Tinea Capitis

Preferred regimen: Griseofulvin PO 10-20mg/kg/day for at least 6 weeks (Preferred for children).
Alternative regimens: Terbinafine PO 62.5mg/day if <20kg; 125 mg/day if 20-40kg; 250mg/day if >40kg OR Itraconazole PO 4-6mg/kg pulsed dose weekly.

Note: Nistatin is not effective in the treatment of dermatophytosis.

Tinea barbae Return to Top

Tinea Barbae

Preferred regimen: Terbinafine PO 250mg/day for 4 weeks.
Alternative regimen: Itraconazole PO 200mg/day for 2 weeks.

Tinea incognito Return to Top

Tinea Incognito

Preferred regimen: Stop topical steroids and treat with topical 1% terbinafine cream for 6 weeks.

Tinea manuum Return to Top

Tinea Manuum

Preferred regimen: topical or systemic terbinafine PO 250 mg/day por 2-4 weeks.

Tinea versicolor Return to Top

Tinea Versicolor

Preferred regimen: Itraconazole 200mg daily for a week.
Alternative regimen: Ketoconazole 200mg daily for 4 weeks.

Majocchi's granuloma Return to Top

Majocchi's Granuloma

Preferred regimen: Terbinafine PO 250mg/day for 2-4 weeks.
Alternative regimen: Itraconazole 200mg PO bid for 1 week, per month for 2 months.

Onychomycosis Return to Top

Onychomycosis^[210]

10.1 Fingernails

Preferred regimen: Terbinafine PO 250mg/day for 6 weeks OR Itraconazole PO 200mg twice a day for a week a month for 2 months (European guidelines).

10.2 Toenails

Preferred regimen: Toenails Terbinafine PO 250mg/day for 12 weeks OR Itraconazole PO 200mg/day for 12 weeks (U.S. guidelines) OR Itraconazole PO 200mg twice a day for a week a month for 3 months (European guidelines).

Note (1): There is no evidence that combining systemic and topic treatments has any benefit to the patient.

Histoplasmosis Return to Top

1. Adult treatment: ^[211]

1.1 Pulmonary

1.1.1 Acute pulmonary histoplasmosis

1.1.1.1 Moderate severe or severe

Preferred regimen (1): Lipid formulation of Amphotericin B (3.0–5.0 mg/kg IV q12h for 1–2 weeks) THEN Itraconazole (200 mg tid for 3 days THEN 200 mg bid for a total of 12 weeks).
Preferred regimen (2): Methylprednisolone (0.5–1.0 mg/kg IV q24h) during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress
Alternative regimen: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg q24h IV) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity.
Note (1): In severe cases, cases accompanied by respiratory insufficiency, or hypoxemia, anecdotal reports suggest that corticosteroid therapy may hasten recovery
Note (2): The pulmonary infiltrates should be resolved on the chest radiograph before antifungal therapy is stopped.

1.1.1.2 Mild to moderate:

Treatment is usually unnecessary
Preferred regimen for patients who continue to have symptoms for >1 month: Itraconazole (200 mg tid for 3 days {{then} 200 mg qd OR bid for 6–12 weeks)
Note (1): Antifungal treatment is unnecessary in patients with mild symptoms caused by acute pulmonary histoplasmosis

1.1.2 Chronic cavitary pulmonary histoplasmosis:

Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for at least 1 year) is recommended
Note (1): Blood levels of itraconazole should be obtained after the patient has been receiving this agent for at least 2 weeks to ensure adequate drug exposure
Note (2): Patients with underlying emphysema often develop progressive pulmonary disease, which is characterized by cavities with surrounding inflammation after infection with hysotplasma capsulatum

1.1.3 Broncholithiasis

Antifungal treatment is not recommended
Note: Bronchoscopic or surgical removal of the broncholith is recommended

1.1.4 Pulmonary nodules (Histoplasmomas)

Antifungal treatment is not recommended**
Note: There is no evidence that antifungal agents have any effect on histoplasmomas or that histoplasmomas contain viable organisms.

1.2 Mediastinitis

1.2.1 Mediastinal lymphadenitis

1.2.1.1 Asymptomatic cases

Treatment is usually unnecessary

1.2.1.2 Patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for > 1 month

Itraconazole (200 mg 3 tid for 3 days and THEN 200 mg qd or bid for 6–12 weeks)

1.2.1.2 Severe cases with obstruction or compression of contiguous structures

Preferred regimen: Prednisone (0.5–1.0 mg/kg qd [maximum 80 mg qd] in tapering doses over 1–2 weeks)
Note (1): Antifungal treatment is unnecessary in most patients with symptoms due to mediastinal lymphadenitis
Note (2): Itraconazole is recommended for 6–12 weeks to reduce the risk of progressive disseminated disease caused by corticosteroid-induced immunosuppression in patients who are given corticosteroids and in patients whose symptoms last longer than 1 month.

1.2.2 Mediastinal granuloma

1.2.2.1 Asymptomatic cases

Treatment is usually unnecessary

1.2.2.2 Symptomatic cases

Preferred regimen: Itraconazole (200 mg 3 times qd for 3 days and THEN qd or bid for 6–12 weeks)
Note (1): Itraconazole is appropriate for symptomatic cases but there are no controlled trials to prove its efficacy.
Note (2): There is no evidence that mediastinal granuloma evolves into mediastinal fibrosis. Thus treatment with either surgery or itraconazole should not be used to prevent the development of mediastinal fibrosis

1.2.3 Mediastinal fibrosis

Antifungal treatment is not recommended**

1.2.3.1 If clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma

Preferred regimen: Itraconazole (200 mg qd or bid for 12 weeks)
Note: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
Note (2): Mediastinal fibrosis is characterized by invasive fibrosis that encases mediastinal or hilar nodes and that is defined by occlusion of central vessels and airways

1.3 Pericarditis:

1.3.1 Mild cases

Preferred regimen: Nonsteroidal anti-inflammatory therapy

1.3.2 Patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy

Prednisone (0.5–1.0 mg/kg qd [maximum, 80 mg qd] in tapering doses over 1–2 weeks)

1.3.3 If corticosteroids are administered

Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for 6–12 weeks)
Note (1): Pericardial fluid removal is indicated for patients with hemodynamic compromise.
Note (2): Pericarditis occurs as a complication of inflammation in adjacent mediastinal lymph nodes in patients with acute pulmonary histoplasmosis.

1.4 Central nervous system histoplasmosis

Preferred regimen: Liposomal Amphotericin B (5.0 mg/kg qd for a total of 175 mg/kg given over 4–6 weeks) followed by Itraconazole (200 mg 2 or 3 times qd) for at least 1 year and until resolution of cerebro spinal fluid abnormalities including Histoplasma antigen levels.
Note: Blood levels of Itraconazole should be obtained to ensure adequate drug exposure

1.5 Rheumatologic syndromes

1.5.1 Mild cases

Preferred regimen: Nonsteroidal anti-inflammatory therapy

1.5.2 Severe cases

Preferred regimen: Prednisone (0.5–1.0 mg/kg qd [maximum, 80 mg qd] in tapering doses over 1–2 weeks)

1.5.3 Corticosteroids administration

Itraconazole (200 mg 3 times tid for 3 days and THEN qd or bid for 6–12 weeks)
Note (1): If corticosteroids are used, concurrent itraconazole treatment is recommended to reduce the risk of progressive infection
Note (2): Bone or joint involvement is very rare in progressive disseminated histoplasmosis but it should not be overlooked.

1.6 Progressive disseminated histoplasmosis

1.6.1 Moderately severe to severe disease

Preferred regimen: Liposomal Amphotericin B (3.0 mg/kg qd) is recommended for 1–2 weeks followed by oral Itraconazole (200 mg 3 times qd for 3 days and THEN 200 mg bid for a total of at least 12 months)
Note (1): Substitution of another lipid formulation at a dosage of 5.0 mg/kg qd may be preferred in some patients because of cost or tolerability
Note (2): The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity

1.6.2 Immunosupressed patients

Lifelong suppressive therapy with Itraconazole (200 mg qd)

1.6.3 Mild to moderate disease

Itraconazole (200 mg tid for 3 days and then bid qid for at least 12 months)
Note (1): Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy
Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
Note (3): Antigen levels should be measured during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.
Note (4): Progressive disseminated histoplasmosis is fatal without therapy and treatment with either Amphotericin B or Itraconazole is highly effective. Among patients with AIDS and moderately severe to severe disseminated histoplasmosis, the rate of response was higher (88% vs. 64%) and the mortality rate was lower (2% vs. 13%) among recipients of liposomal amphotericin B (3 mg/kg qd for 1–2 weeks) than among recipients of the deoxycholate formulation.

1.7 Prophylaxis recommended for immunosuppressed patients

Preferred regimen: Itraconazole (200 mg qd) in patients with HIV infection with CD4 cell counts <150 cells/mm3 in specific areas of endemicity where the incidence of histoplasmosis is >10 cases per 100 patient-years
Note: Prophylaxis with Itraconazole (200 mg qd) may be appropriate in specific circumstances in other immunosuppressed patients

1.8 Performance Measures

Preferred regimen: Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of Amphotericin B
Note: When other azole agents are used, the medical record should document the specific reasons that Itraconazole was not used and why other azoles were used.
14.1 Severe or moderately severe histoplasmosis
Preferred regimen: Amphotericin B
Note: When Amphotericin B is used the patient's electrolyte level renal function and blood cell count should be monitored several times per week and documented in the medical record.
Note (2): Itraconazole drug levels should be measured during the first month in patients with disseminated or chronic pulmonary histoplasmosis and these levels should be documented in the medical record as well as the physician's response to levels that are too low.
Note (3): Itraconazole should not be given to patients receiving contraindicated medications (i.e., pimozide, quinidine, dofetilide, lovastatin, simvastatin, midazolam, and triazolam). Reasons for deviation from this practice should be documented in the medical record.

2. Pregnancy treatment

Preferred regimen: Lipid formulation Amphotericin B (3.0–5.0 mg/kg qd for 4–6 weeks) is recommended
Prefered regimen low risk for nephrotoxicity: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation
Note (1): If the newborn shows evidence for infection, treatment is recommended with Amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks)
Note (2): Unique issues in pregnancy include the risk of teratogenic complications of azole therapy and of transplacental transmission of Histoplasma capsulatum to the fetus

3. Children treatment

3.1 Acute pulmonary histoplasmosis
Treatment indications and regimens are similar to those for adults, except that Amphotericin B deoxycholate (1.0 mg/kg daily) is usually well tolerated and the lipid preparations are not preferred
Note: Itraconazole dosage: 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation

Progressive disseminated histoplasmosis
Prefered regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 4–6 weeks)
Alternative regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 2–4 weeks) followed by itraconazole (5.0–10.0 mg/kg qd in 2 divided doses) to complete 3 months of therapy.
Immunosuppressed patients if immunosuppression cannot be reversed and patients in relapse despite appropiate therapy

Preferred regimen: Lifelong suppressive therapy with Itraconazole (5.0 mg/kg qd up to 200 mg qd)

Note (1): Longer therapy may be needed for patients with severe disease, immunosuppression, or primary immunodeficiency syndromes
Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
Note (3): Antigen levels should be monitored during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.

Mucormycosis Return to Top
Mucormycosis^[212]

Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.
Preferred regimen (1): Amphotericin B Deoxycholate 1.0-1.5 mg/kg/day IV q24h
Preferred regimen (2): Lipid Amphotericin B 5-10 mg/kg/day IV q24h
Preferred regimen (3): Amphotericin B lipid complex 5-7.5 mg/kg/day IV q24h
Alternative regimen (1):Caspofungin 70 mg IV load dose, 50 mg/day for >2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

Pediatric dose: Caspofungin 50 mg/m² IV q24h PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

Alternative regimen (2): Micafungin OR Anidulafungin 100 mg/day for 2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h

Pediatric dose: Micafungin 4 mg/kg/day; Micafungin 10mg/kg/day for low-birth weight infants; Anidulafungin 1.5 mg/kg/day

Alternative regimen (3): Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
Alternative regimen (4): Posaconazole 800 mg/day PO qid or bid
Alternative regimen (5): Initial: Isavuconazole 200 mg PO/IV q8h for 6 doses; maintenance: 200 mg PO/IV qd
Note (1): start maintenance dose 12 to 24 hours after the last loading dose.
Note (2): For salvage therapy: (Posaconazole 800 mg/day PO qid or bid ± Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR (Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR Granulocyte transfusions (for persistently neutropenic patients) ∼10ˆ9 cells/kg OR Recombinant cytokines G-CSF 5 μg/kg/day, GM-CSF 100–250 μg/m², or IFN-g at 50 μg/m² for those with body surface area ≥ 0.5 m² and 1.5 μg/kg for those with body surface area <0.5 m²

Penicilliosis Return to Top

Penicilliosis treatment

1. Mild disease

Preferred regimen: Itraconazole 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy^[213]
Alternative regimen: Voriconazole 400 mg PO bid on day 1 THEN 200 mg PO bid for 12 weeks^[214]

2. Moderate-severe disease

Preferred regimen: Liposomal Amphotericin B 3-5 mg/kg/day IV qd OR Amphotericin B lipid complex 5 mg/kg/day IV qd for 2 weeks THEN Itraconazole 200 mg PO bid for 10 weeks^[215]
Alternative regimen: Voriconazole 6 mg/kg IV q12h on day 1 THEN 4 mg/kg q12h for at least 3 days THEN Voriconazole 200 mg PO bid for a total of 12 weeks^[214]

3. Maintenance therapy^[216]

Preferred regimen Itraconazole 200 mg PO qd
Alternative regimen: Voriconazole 200 mg PO bid

Note: Voriconazole and Itraconazole use require serum levels to be monitored to ensure adequate absorption.

Sporotrichosis Return to Top

^[217]

Lymphocutaneous/cutaneous

Preferred regimen: Itraconazole 200mg PO qd
Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg PO bid OR Saturated solution potassium iodide with increasing doses OR Fluconazole 400–800 mg PO qd OR local hyperthermia
Note (1): Treat for 2–4 weeks after lesions resolved
Note (2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) q8h, increasing as tolerated to 40–50 drops q8h

Osteoarticular

Preferred regimen: Itraconazole 200mg PO bid for 12 months
Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV
Note (1): Switch to Itraconazole after favorable response if AmB used
Note (2): Treat for a total of at least 12 months

Pulmonary

Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d IV THEN Itraconazole 200 mg PO bid OR surgical removal
Note (1): Treat severe disease with an AmB formulation followed by Itraconazole
Note (2): Treat less severe disease with Itraconazole
Note (3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease

Meningitis

Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
Note (1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
Note (2): Treat for a total of at least 12 months.
Note (3): May require long-term suppression with Itraconazole.

Disseminated

Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
Note(2): Treat for a total of at least 12 months.
Note(3): May require long-term suppression with Itraconazole.

Pregnant women

Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV for severe sporotrichosis
Preferred regimen(2): Local hyperthermia for cutaneous disease.
Note (1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
Note (2): Azoles should be avoided.

Children

Preferred regimen:

Mild disease: Itraconazole 6–10 mg/kg/day PO (400 mg/day maximum)
Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day IV followed by Itraconazole 6–10 mg/kg PO up to a maximum of 400 mg PO daily, as step-down therapy

Alternative regimen: Saturated solution potassium iodide with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) q8h and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops q8h, whichever is lowest

Pneumocystis jiroveci Return to Top

1. Preventing First Episode of PCP (Primary Prophylaxis)^[218]

Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO bid
Alternative regimen (2): Dapsone 50 mg PO AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
Alternative regimen (3): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
Alternative regimen (5): Atovaquone 1500 mg PO qd with food
Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO daily with food

2. Treatment of Pneumocystis Pneumonia^[219]

2.1. Moderate to Severe PCP

Preferred regimen: TMP-SMX (TMP 15–20 mg and SMX 75–100 mg)/kg/day IV given q6h or q8h
Note: May switch to PO after clinical improvement
Alternative regimen (1): Pentamidine 4 mg/kg IV once daily infused over at least 60 minutes
Note: May reduce the dose to 3 mg/kg IV once daily because of toxicities.
Alternative regimen (2): Primaquine 30 mg (base) PO once daily AND (Clindamycin [IV 600 mg q6h or 900 mg q8h] or [PO 450 mg q6h or 600 mg q8h])

Note (1): Duration of PCP treatment is 21 days
Note (2): Adjunctive corticosteroid may be indicated in some moderate to severe cases.Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy) (AI):
Note (3): Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy)

Days 1–5 40 mg PO BID
Days 6–10 40 mg PO daily
Days 11–21 20 mg PO daily

2.2. Mild to Moderate PCP

Preferred regimen: TMP-SMX (TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day), given PO in 3 divided doses OR TMP-SMX Double-Strength(DS) - 2 tablets tid
Alternative regimen (1): Dapsone 100 mg PO daily AND TMP 15 mg/kg/day PO (3 divided doses)
Alternative regimen (2): Primaquine 30 mg (base) PO daily AND Clindamycin PO (450 mg q6h or 600 mg q8h)
Alternative regimen (3): Atovaquone 750 mg PO BID with food

Note: Duration of PCP treatment is 21 days

3. Preventing Subsequent Episode of PCP (Secondary Prophylaxis)^[220]

Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO BID
Alternative regimen (2): Dapsone 50 mg PO daily AND (Pyrimethamine 50 mg + Leucovorin 25 mg) PO weekly
Alternative regimen (3): Dapsone 200 mg AND Pyrimethamine 75 mg AND Leucovorin 25 mg PO weekly
Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
Alternative regimen (5): Atovaquone 1500 mg PO daily with food
Alternative regimen (6): Atovaquone 1500 mg AND Pyrimethamine 25 mg AND Leucovorin 10 mg PO daily with food

Mycobacteria

Mycobacterium tuberculosis Return to Top

1. Standard Regimens for new patients ^[221]

1.1 Adult

1.1.1 Initial phase

Preferred regimen: Isoniazid 300 mg PO (5 mg/kg/day) qd for 8 weeks AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 8 weeks AND Pyrazinamide 2 g PO (25 mg/kg/day) qd for 8 weeks AND Ethambutol 1.6 g PO (15 mg/kg/day) qd for 8 weeks
Alternative regimen (1): Isoniazid 300 mg/day PO for 2 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO for 2 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO for 2 weeks (25 mg/kg/day) AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day), followed by Isoniazid 300 mg/day PO twice weekly for 6 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly for 6 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO twice weekly for 6 weeks AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day)
Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 8 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 8 weeks (10 mg/kg/day) AND Pyrazinamide 2g/day PO thrice weekly for 8 week (25 mg/kg/day) AND Ethambutol 1.6 g PO thrice weekly for 8 weeks (15 mg/kg/day)

1.1.2 Continuation phase

Preferred regimen (1): Isoniazid 300 mg PO (5 mg/kg/day) qd AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 18 weeks
Preferred regimen (2): Isoniazid 300 mg PO twice weekly (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly (10 mg/kg/day) for 18 weeks
Alternative regimen (1): Isoniazid 300 mg/day PO biweekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO biweekly for 18 weeks (10 mg/kg/day)
Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 18 weeks (10 mg/kg/day)

1.2 Pediatric

1.2.1 Initial phase

Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day) AND Pyrazinamide 35 mg/kg PO (Maximum, 2 g/day) AND Ethambutol 20 mg/kg PO (Maximum, 1.6 g/day), each for 8 weeks

1.2.2 Continuation phase

Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day), each drug daily for 18 weeks

2. MDR Tuberculosis ^[222]

2.1 Adult

Preferred regimen: 4 agents combination

Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
Agent 2: Capreomycin 15 mg/kg OR Kanamycin 15 mg/kg OR Amikacin 7.5-10 mg/kg OR Streptomycin 12–18 mg/kg
Agent 3: Levofloxacin 500-1000 mg OR Moxifloxacin 400 mg OR Ofloxacin 400 mg
Agent 4: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 mg/kg OR Para-aminosalicylic acid 8-12 g/day IV q8-12h

2.2 Pediatric

Preferred regimen: 4 agents combination

Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15-20 mg/kg OR Rifabutin 5 mg/kg
Agent 2: Capreomycin 15-30 mg/kg (Maximum: 1000 mg) OR Kanamycin 15-30 mg/kg (Maximum: 1000 mg) OR Amikacin 15-22.5 mg/kg (Maximum: 1000 mg) OR Streptomycin 12-18 mg/kg AND
Agent 3: Levofloxacin 7.5-10 mg/kg OR Moxifloxacin 7.5-10 mg/kg OR Ofloxacin 15-20 mg/kg/day q12h (Maximum: 800 mg)
Agent 4: Ethionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h(Maximum: 12,000 mg)

3. XDR Tuberculosis ^[223]

3.1 Adult

Preferred regimen: 3 agents combination

Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
Agent 2: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 kg/mg OR Para-aminosalicylic acid 8-12 g/day q8-12h
Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate 500 mg/125 mg q12h OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg

3.2 Pediatric

Preferred regimen: 3 agents combination

Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15 mg/kg OR Rifabutin 5 mg/kg

Agent 2: Ethionamide 15-20 mg/kg (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h

Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg

Mycobacterium abscessus Return to Top
1.Limited, localized extrapulmonary disease ^[224]

Preferred regimen: Clarithromycin 500 mg PO bid ± Amikacin 10-15 mg/kg/day IV or 25 mg/kg three times weekly for 4 months

Alternative regimen (1): Amikacin AND Cefoxitin 12 g/day PO for two weeks
Note: until clinical improvement in severe cases

Alternative regimen (2): Amikacin AND Imipenem 500 mg IV q6-8h for two weeks
Note(1): Until clinical improvement in severe cases
Note(2): Osteomyelitis should be treated for as least 6 months; Infected foreign bodies should be removed

2.Pulmonary or serious extrapulmonary disease

Preferred regimen: Clarithromycin 500 mg PO bid AND Amikacin 15 mg/kg/day IV AND Cefoxitin 2g IV q4h OR Imipenem 1g IV q6h for at least 2-4 months
Note: If limited by adverse effects THEN Clarithromycin 500 mg PO bid or 1000 mg XR qd OR Azithromycin 250 mg PO qd
Alternative regimen(1): Tigecycline 100 mg IV loading dose THEN 50 mg IV q12h
Note: could be substituted as one of the injectables
Alternative regimen(2): Linezolid 600 mg PO bid or 600 mg PO qd AND Clarithromycin
Note: Could replace parental tx if not tolerated or feasible

Mycobacterium bovis Return to Top

Mycobacterium bovis ^[225]

Note: Is intrinsically resistant to Pyrazinamide (PZA). The treatment of M. bovis is extrapolated from experience with the treatment of PZA-resistant M. tuberculosis
1. Pulmonary and most extrapulmonary disease

Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 7 months

2. Meningitis

Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 10 months

Mycobacterium avium-intracellulare Return to Top

1. Treatment of MAC pulmonary disease ^[226]

1.1 Patients with nodular/bronchiectatic disease

Preferreday regimen: Clarithromycin 1,000 mg three times weekly OR Azithromycin 500–600 mg three times weekly AND Ethambutol 25 mg/kg three times weekly AND Rifampin 600 mg three times weekly
Note: Patients should be treated until culture negative on therapy for 1 year

1.2 Patients with fibrocavitary or severe nodular/bronchiectatic disease

Preferreday regimen: Clarithromycin 500–1,000 mg/day OR Azithromycin 250–300 mg/day OR Rifampin 600 mg/day OR Rifabutin 150–300 mg/day AND Ethambutol 15 mg/kg/day
Note(1): Amikacin OR Streptomycin threetimes-weekly can be used early in therapy
Note(2): Patients should be treated until culture negative on therapy for 1 year

2. Disseminateday MAC disease

Preferreday regimen: Clarithromycin 1,000 mg/day OR Azithromycin 250 mg/day AND Ethambutol 15 mg/kg/day ± Rifabutin 150–350 mg/day

Mycobacterium celatum Return to Top

Mycobacterium celatum ^[227]

Preferred regimen: Clarithromycin AND Ethambutol AND Ciprofloxacin ± Rifabutin

Mycobacterium chelonae Return to Top

Mycobacterium chelonae ^[228]
1. Localized infections

Preferred regimen: Clarithromycin 500 mg PO bid
Alternative regimen: Azithromycin

2. Disseminated or extensive disease

2.1 monotherapy

Preferred regimen: Clarithromycin 500 mg PO bid for 6 months

2.2 multidrug therapy

preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 5 mg/kg IV q24h OR Imipenem 0.5-1 g IV q6h OR Linezolid 600 mg IV/PO q12h/bid for 4-8 weeks
Alternative regimen: Moxifloxacin 400 mg PO qd AND Linezolid 600 mg PO bid
Note(1): During initial treatment, multidrug therapy may prevent development of acquired resistance
Note(2): Total treatment duration is 6 months

3. Keratitis (LASIK-related)

Preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 0.3% 2 gtts q4h AND Gatifloxacin 0.3% 1 gtt q4h OR Moxifloxacin 0.5% 1 gtt q4h

Mycobacterium foruitum Return to Top

Mycobacterium foruitum ^[229]

1. In vitro isolates

Susceptible agents: Amikacin (100%), Ciprofloxacin and Ofloxacin (100%), Sulfonamides (100%), Cefoxitin (50%), Imipenem (100%), Clarithromycin (80%), and Doxycycline (50%)

2. Disease

2.1 M. fortuitum lung disease

At least two agents with in vitro activity against the clinical isolate should be given for at least 12 months of negative sputum cultures

2.2 Serious skin, bone, and soft tissue M fortuitum disease

At least two agents with in vitro activity against the clinical isolate should be given for a minimum of 4 months; For bone infections, 6 months of therapy is recommended

Mycobacterium haemophilum Return to Top

Mycobacterium haemophilum ^[230]

1. In vitro

Susceptible: Amikacin, Clarithromycin, Ciprofloxacin, Rifampin, and Rifabutin
Less susceptible: Doxycycline and Sulfonamides

2. Infection

2.1 Disseminated disease

Preferred regimen: Clarithromycin AND Rifampin AND Rifabutin AND Ciprofloxacin

Mycobacterium genavense Return to Top

Mycobacterium genavense ^[231]

Susceptibility: Amikacin, Rifamycin, Fluoroquinolones, Streptomycin, and Macrolides
Note(1): Ethambutol has limited activity
Note(2): Optimal therapy is not determined, but multidrug therapies including Clarithromycin appear to be more effective than those without Clarithromycin

Mycobacterium gordonae Return to Top

Mycobacterium gordonae ^[232]

Preferred regimen: Ethambutol OR Rifabutin OR Clarithromycin OR Linezolid OR Fluoroquinolones

Mycobacterium kansasii Return to Top

Mycobacterium kansasii ^[233]

1. pulmonary disease

Preferred regimen: Rifampin 10 mg/kg/day (Maximum, 600 mg) PO AND Ethambutol 15 mg/kg/ day PO AND Isoniazid 5 mg/kg/day (Maximum 300 mg) PO AND Pyridoxine 50 mg/day PO
Note: Treatment duration for M. kansasii lung disease should include 12 months of negative sputum cultures

2. Rifampin-resistant M. kansasii disease

Preferred regimen: Clarithromycin OR Azithromycin OR Moxifloxacin OR Ethambutol OR Sulfamethoxazole OR Streptomycin
Note(1): Use three-drug regimen
Note(2): Patients undergoing therapy for M. kansasii lung disease should have close clinical monitoring with frequent sputum examinations for mycobacterial culture throughout therapy

3. Disseminated M. kansasii disease

Note: The treatment regimen for disseminated disease should be the same as for pulmonary disease

Mycobacterium marinum Return to Top

Mycobacterium marinum ^[234]

1. In vitro M. marinum isolates

Susceptible: Rifampin, Rifabutin, Ethambutol, Clarithromycin, Sulfonamides, and Trimethoprim sulfamethoxazole
Intermediately susceptible: Streptomycin, Doxycycline, and Minocycline
Resistant: Isoniazid and Pyrazinamide
Note: Two active agents for 1 to 2 months after resolution of symptoms, typically 3 to 4 months in total

2. Infection

2.1 skin and soft tissue infections

Preferred regimen (1): Clarithromycin AND Ethambutol
Preferred regimen (2): Ethambutol AND Rifampin
Note: Azithromycin can replace Clarithromycin

2.2 osteomyelitis or deep structure infection

Preferred regimen: Clarithromycin AND Ethambutol AND Rifampin

Mycobacterium scrofulaceum Return to Top

Mycobacterium scrofulaceum ^[235]

Susceptibility data are lacking and standard treatment regimens for M. scrofulaceum are controversial, emphasizing the need to perform susceptibility testing on confirmed disease-producing isolates of M. scrofulaceum

Mycobacterium simiae Return to Top

Mycobacterium simiae ^[236]

Preferred regimen: Clarithromycin AND Moxifloxacin AND Trimethoprim/sulfamethoxazole

Mycobacterium ulcerans Return to Top

Mycobacterium ulcerans ^[237]

1. Preulcerative lesions

Excision and primary closure, Rifampin monotherapy, or heat therapy

2. Established ulcers

Most antimycobacterial agents are ineffective for the treatment of the ulcer; Surgical debridement combined with skin grafting is the usual treatment of choice

3. Control complications of the ulcer

Preferred regimen: Clarithromycin AND Rifampin

Mycobacterium xenopi Return to Top

Mycobacterium xenopi ^[238]

1. The cornerstone of therapy for M. xenopi

Preferred regimen: Clarithromycin AND Rifampin AND Ethambutol
Note: Therapy should be continued until the patient has maintained negative sputum cultures while on therapy for 12 months

2. Pulmonary disease

Preferred regimen: INH AND Rifabutin OR Rifampin AND Ethambutol AND Clarithromycin ± Streptomycin
Note: A quinolone, preferably Moxifloxacin, could be substituted for one of the antituberculous drugs

3. Extrapulmonary disease

Note: Therapy for extrapulmonary disease would include the same agents as for pulmonary disease

Mycobacterium leprae Return to Top

Mycobacterium leprae ^[239]

1. Multibacillary Leprosy (Skin smear positive)

1.1 Adult

Preferred regimen: Dapsone 100 mg/day PO AND Rifampin 600 mg PO 4 times per week AND Clofazimine 50 mg PO qd for 12-24 months
Note: Clofazimine should be supplemented by loading dose 300 mg PO monthly

1.2 Pediatric

1.2.1 < 35 kg

Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 450 mg PO for 12-24 months

1.2.2 < 20 kg

Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 300 mg PO for 12-24 months

1.2.3 < 12 kg

Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 150 mg PO for 12-24 months

2. Paucibacillary Leprosy (Skin Smear negative)

Preferred regimen: Rifampin 600 mg PO once a month for 6 months AND Dapsone 100 mg PO qd for 6 months

3. Erythema Nodosum Leprosum (ENL)

3.1 Mild

Preferred regimen: Rest affect limb, analgesics, follow-up twice a week, check for iridocyclitis; Chloroquine OR Aspirin may be useful

3.2 Severe (numerous nodules + fever, ulcerating/pustular ENL, visceral involvement, nodules + neuritis, recurrent ENL)

Preferred regimen: Prednisolone 30-40 mg/day PO for 1-2 weeks THEN taper over 12 weeks
Alternative regimen (1): (If unresponsive to corticosteroids or if risk of corticosteroids prevent administration) Clofazimine 100 mg PO tid for maximum of 12 weeks THEN taper the dose to 100 mg PO bid for 12 weeks THEN 100 mg qd for 12-24 weeks
Alternative regimen (2): (if not contraindicated) Thalidomide 200-400 mg/day PO THEN 50-100 mg/day after 1-2 weeks

4. Reversal Reaction

Preferred regimen: Prednisolone start with 40 mg/day PO THEN taper by 10 mg twice a week for 12 weeks

Mycobacterium smegmatis Return to Top

Mycobacterium smegmatis ^[240]

1. Mild disease

Preferred regimen: Doxycycline PO AND Trimethoprim sulfamethoxazole PO

2. Severe disease

Preferred regimen: Amikacin IV OR Imipenem IV

Mycobacterium immunogenum Return to Top

Mycobacterium immunogenum ^[241]

In vitro

Susceptible: Amikacin and Clarithromycin
Resistant: Ciprofloxacin, Doxycycline, Cefoxitin, Tobramycin, and Sulfamethoxazole
Note: The optimal therapy for this organism is unknown; however, successful therapy is likely difficult due to the extensive antibiotic resistance of the organism

Mycobacterium malmoense Return to Top

Mycobacterium malmoense^[242]

1. In vitro

Susceptible: Ethambutol, Ethionamide, Kanamycin, and Cycloserine
Resistant: INH, Streptomycin, Rifampin, and Capreomycin

2. Pulmonary M. malmoense infection

Preferred regimen: INH AND Rifampin AND Ethambutol ± Quinolones AND Macrolides

Mycobacterium mucogenicum Return to Top

Mycobacterium mucogenicum ^[243]

In vitro susceptible agents: Aminoglycosides, Cefoxitin, Clarithromycin, Minocycline, Doxycycline, Quinolones, Trimethoprim/sulfamethoxazole, and Imipenem

Mycobacterium szulgai Return to Top

Mycobacterium szulgai ^[244]^[245]

1. in vitro susceptibility

M. szulgai is susceptible in vitro to most antituberculous drugs including Quinolones and newer Macrolides

2. Infection

2.1 Pulmonary infection

Three- or four-drug regimen based on susceptibility that includes 12 months of negative sputum cultures while on therapy

2.2 Extrapulmonary infection

Combination anti-tuberculous medications based on in vitro susceptibilities for 4-6 months

Mycobacterium terrae Return to Top

Mycobacterium terrae ^[246]

1. In vitro susceptibility

All six of the isolates from a single center and 90% or more of an additional 22 isolates of M. terrae complex were susceptible to Ciprofloxacin and Sulfonamides. Recently, 11 isolates of M. terrae complex were also shown to be susceptible to Linezolid

2. Antimicrobial therapy

Based on in vitro susceptibility results

Parasites – Intestinal Protozoa

Balantidium coli Return to Top

Blastocystis hominis Return to Top

Blastocystis^[247]

Preferred regimen (1): Metronidazole 750 mg PO tid or 1.5 g qd for 10 days

Preferred regimen (2): Trimethoprim-sulfamethoxazole 1 DS PO bid or 2 DS PO qd for 7 days

Preferred regimen (3): Iodoquinol 650 mg PO tid for 20 days

Preferred regimen (4): Nitazoxanide 500 mg PO bid for 3 days

Preferred regimen (5): Paromomycin 25-35 mg/kg/day PO tid for 7 days
Note (1): Treatment of asymptomatic infections is unnecessary
Note (2): One double strength tablet contains 160 mg trimethoprim/800 mg sulfamethoxazole

Cryptosporidium parvum Return to Top

1. Immunocompetent^[248]

Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.

2. HIV^[249]

Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days

3. HIV and Immunodeficiency^[250]

Preferred regimen: Effective antiretroviral therapy
Note: Nitazoxanide is not licensed for immunodeficient patients

Cryptosporidium hominis Return to Top

1. Immunocompetent^[251]

Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.^[252]

2. HIV^[253]

Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days

3. HIV and Immunodeficiency^[254]

Preferred regimen: Effective antiretroviral therapy
Note: Nitazoxanide is not licensed for immunodeficient patients

Cyclospora cayetanensis Return to Top

Cyclosporiasis^[255]

Preferred regimen: Trimethoprim-Sulfamethoxazole double-strength (160 mg TMP/800 mg SMX) 1 tablet PO bid for 7-10 days
Alternative regimen (1): Ciprofloxacin 500 mg PO bid for 7 days
Alternative regimen (2): Nitazoxanide 500 mg PO bid for 7 days
Note: Treatment is continued for 7 days in immunocompetent hosts and for 7 to 10 days in patients with HIV infection.

Dientamoeba fragilis Return to Top

Dientamoebiasis^[256]^[257]^[258]

Preferred regimen: Iodoquinol 650 mg PO tid for 20 days
Alternative regimen (1): Paromomycin 25–35 mg/kg/day PO in three divided doses for 7 days
Alternative regimen (2): Metronidazole 500–750 mg PO tid for 10 days
Alternative regimen (3): Tetracycline 500 mg PO qid for 10 days

1.1 Treatment in pregnancy

The use of Iodoquinol in pregnancy is limited, and risk to the embryo-fetus is unknown, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Oral dose of Paromomycin generally is poorly absorbed from the gastrointestinal tract, with minimal, if any, systemic availability.
Metronidazole is in pregnancy category B. Data on the use of this drug in pregnant women are conflicting. The available evidence suggests use during pregnancy has a low risk of congenital anomalies. May be used during pregnancy in those patients who will clearly benefit from the drug, although its use in the first trimester is generally not advised.

1.2 Treatment during lactation

Iodoquinol should be used with caution in breastfeeding women.
Oral dose of Paromomycin is unlikely to be excreted in breast milk, and the drug generally is poorly absorbed from the gastrointestinal tract.
Metronidazole should be used during lactation only if the potential benefit of therapy to the mother justifies the potential risk to the infant.

1.3 Treatment in pediatric patients

Iodoquinol 30–40 mg/kg/day (maximum 2 g) PO in 3 doses for 􏰄20 days. The safety of iodoquinol in children has not been established.
Paromomycin 25–35 mg/kg/day PO in 3 doses􏰄 for 7 days. The safety of oral dose in children has not been formally evaluated. However, the safety profiles likely are comparable in children and adults.
Metronidazole 35–50 mg/kg/day PO in 3 doses for􏰄 10 days. The safety in children has not been established, is listed as an antiamebic and antigiardiasis medicine on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
Tetracycline 40 mg/kg/day (maximum 2 g) PO in 4 doses for􏰄 10 days

Entamoeba histolytica Return to Top

1. Amebic Liver Abscess^[259]

Preferred regimen: (Metronidazole 750 mg PO tid for 10 days OR Tinidazole 2 g PO qd for 5 days) AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
Alternative regimen (1): Nitazoxanide 500 mg bid for 10 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
Alternative regimen (2): Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
Alternative regimen (2): Tinidazole 2 g PO qd for 5 days

2. Amebic Colitis^[260]

Preferred regimen: Metronidazole 500-750 mg PO tid for 7-10 days. Pediatric dose: 35-50 mg/kg per day tid AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
Alternative regimen: Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)

3. Asymptomatic Intestinal Colonization^[261]

Preferred regimen: Paromomycin 30 mg/kg/day PO tid for 5-10 days
Alternative regimen (1): Diloxanide furoate 500 mg PO tid for 10 days
Alternative regimen (2): Diiodohydroxyquin 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children

Giardia lamblia Return to Top

1. Giardiasis^[262]^[263]

1.1 Adult

Preferred regimen (1): Metronidazole 250 mg tid 5–7 days
Preferred regimen (2): Tinidazole 2 g single dose
Preferred regimen (3): Nitazoxanide 500 mg PO bid (with food)
Alternative regimen (1): Paromomycin 500 mg tid 3 5–10 days
Alternative regimen (2): Quinacrine 100 mg tid 3 5–7 days
Alternative regimen (3): Furazolidone 100 mg qid 3 7–10 days

1.2 Pediatric

Preferred regimen (1): Metronidazole 5 mg/kg tid 3 5–7 days
Preferred regimen (2): Tinidazole 50 mg/kg single dose (max, 2 g)
Preferred regimen (3): Nitazoxanide 100 mg PO bid for age 1-3 years or 200 mg PO bid for age 4-11 years (with food)
Alternative regimen (1): Paromomycin 30 mg/kg/day in 3 doses 3 5–10 days
Alternative regimen (2): Quinacrine 2 mg/kg tid 3 7 days
Alternative regimen (3): Furazolidone 2 mg/kg qid 3 10 days

Cystoisospora belli Return to Top

1. Cystoisospora belli treatment^[264]

1.1 Immunocompetent hosts

In the immunocompetent hosts, symptoms of Cystoisospora infection are usually self-limited.
Antimicrobial therapy to immunocompetent patients may be considered if symptoms do not start to resolve spontaneously after 5 to 7 days (depending upon severity)
Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO bid for 7-10 days
Alternative regimen (1) (for patients who are allergic to or intolerant of TMP-SMX): Pyrimethamine 50-75 mg/day PO qd or divided in 2 equal doses AND Leucovorin 10–25 mg PO qd
Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days (second-line alternative)

1.1.1 In pregnancy

TMP-SMX should be avoided near-term because of the potential for hyperbilirubinemia and kernicterus in the newborn.
Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

1.1.2 During lactation

TMP-SMX generally should be avoided by women when nursing infants who are premature, jaundiced, ill, or stressed, or who have glucose-6-phosphate dehydrogenase deficiency.
The American Academy of Pediatrics classifies Ciprofloxacin as usually compatible with breastfeeding, whereas the World Health Organization recommends avoiding Ciprofloxacin while breastfeeding and CDC recommends Ciprofloxacin should be used during lactation only if the potential benefit justifies the potential risk to the fetus.

1.1.3 In pediatric patients

The use of TMP-SMX in children less than 2 months of age generally is not recommended.
Available evidence is conflicting regarding the potential for growth defects and arthropathies in exposed children. Use of Ciprofloxacin in children requires assessment of potential risks and benefits.

1.2 Immunocompromised hosts

Preferred regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV qid for 10 days
Preferred regimen (2): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV bid for 7-10 days
Note (1): One approach is to start with TMP-SMX (160 mg/800 mg) bid regimen first, and increase daily dose and/or duration (up to 3–4 weeks) if symptoms worsen or persist.
Note (2): IV therapy is recommended for patients with potential or documented malabsorption.
Alternative regimen (1): Pyrimethamine 50–75 mg PO qd AND Leucovorin 10–25 mg PO qd
Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days

2. Cystoisospora belli prophylaxis^[265]

2.1 Primary prophylaxis

Insufficient evidence is available to support a general recommendation for primary prophylaxis for Cystoisosporiasis per se, especially for U.S. travelers in isoporiasis-endemic areas.

2.2 Secondary prophylaxis (preventing recurrence in patients with CD4 count < 200 cells/mm³)

Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO 3 times weekly
Alternative regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO qd
Alternative regimen (2): Trimethoprim-sulfamethoxazole 320 mg/1600 mg PO 3 times weekly
Alternative regimen (3): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
Alternative regimen (4): Ciprofloxacin 500 mg PO 3 times weekly (second-line alternative)
Note (1): Criteria for discontinuation of chronic maintenance therapy: sustained increase in CD4 count > 200 cells/mm³ for > 6 months in response to ART and without evidence of active Cystoisospora belli infection
Note (2): Because of concerns about possible teratogenicity associated with first-trimester drug exposure, clinicians may withhold secondary prophylaxis during the first trimester and treat only symptomatic infection.

Microsporidiosis Return to Top

1. Ocular^[266]

Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Fumagillin eye drops.

2. Intestinal (diarrhea)^[267]

Preferred regimen:

Adult: Albendazole 400 mg PO bid for 3 weeks for E. intestinalis.
Pediatric: Albendazole 15 mg/kg per day divided into 2 daily doses for 7 days for E. intestinalis.

Note: Fumagillin 20 mg PO tid is the only reported effective treatment for E. bieneusi.

3. Disseminated^[268]

Preferred regimen: Albendazole 400 mg po bid for 3 weeks.

Parasites – Extraintestinal Protozoa

Acanthamoeba

Acanthamoeba Return to Top

1. Granulomatous amoebic encephalitis, meningitis, and disseminated Acanthamoeba disease^[269]^[270]

Preferred regimen (1): Pentamidine AND Itraconazole AND Sulfadiazine AND Flucytosine
Preferred regimen (2): Sulfadiazine AND Fluconazole AND Pyrimethamine
Preferred regimen (3): Sulfadiazine AND Flucytosine AND TMP-SMX
Preferred regimen (4): TMP-SMX AND Rifampin AND Ketoconazole
Preferred regimen (5): Miltefosine AND Amikacin
Preferred regimen (6): Miltefosine AND Voriconazole
Preferred regimen (7): Pentamidine AND Itraconazole AND Flucytosine AND Levofloxacin AND Amphotericin B AND Rifampin
Preferred regimen (8): Pentamidine AND Fluconazole AND Miltefosine
Note: The mainstay of successful treatment includes early diagnosis and combination therapy with pentamidine, azole, sulfonamide, miltefosine, and possibly flucytosine.

2. Cutaneous acanthamoebiasis^[271]^[272]^[273]

Preferred regimen: Pentamidine AND Sulfadiazine AND Flucytosine AND (Itraconazole OR Fluconazole) AND Chlorhexidine topical AND Ketoconazole topical

3. Acanthamoeba keratitis^[274]

Preferred regimen: (Polyhexamethylene biguanide topical OR Chlorhexidine topical) ± (Propamidine topical OR Hexamidine topical)
Note (1): Azole antifungal drugs (Ketoconazole, Itraconazole, Voriconazole) may be considered as oral or topical adjuncts.
Note (2): The duration of therapy for Acanthamoeba keratitis may last six months to a year.
Note (3): Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal medications.
Note (4): The use of corticosteroids to control inflammation is controversial.
Note (5): Penetrating keratoplasty may help restore visual acuity.

Balamuthia mandrillaris

Balamuthia mandrillaris Return to Top

1. Granulomatous Amebic Encephalitis^[275]^[276]

Preferred regimen (1): Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Azithromycin OR Clarithromycin)
Preferred regimen (2): Pentamidine AND Albendazole AND (Itraconazole OR Fluconazole) AND Miltefosine

Naegleria fowleri

Naegleria fowleri Return to Top

Primary amoebic meningoencephalitis^[277]^[278]

Preferred regimen: Amphotericin B 1.5 mg/kg/day bid for 3 days; then 1 mg/kg/day for 6 days AND 1.5 mg/day intrathecal for 2 days; then 1 mg/day intrathecal qd for 8 days.
Note: Investigational drug called miltefosine also available for treatment.

Babesia microti

Babesia microti Return to Top

Babesiosis

1. Mild/moderate disease^[279]

Preferred regimen: Atovaquone 750 mg PO bid AND Azithromycin 600 mg PO qd for 7-10 days

2. Severe disease:

Preferred regimen: Clindamycin 600 mg PO tid AND Quinine 650 mg PO tid for 7–10 days
Preferred regimen: Clindamycin 1.2 g IV q12h
Note (1): For overwhelming infection in asplenic patients and immunocompromised patients, treat for 6 or more weeks.
Note (2): Consider transfusion if 􀂕10% parasitemia.

Leishmania

Leishmania Return to Top

Leishmaniasis

1. Cutaneous Leishmaniasis^[280]

Different Leishmania species cause Old World versus New World (American) cutaneous leishmaniasis. In the Old World (the Eastern Hemisphere), the etiologic agents include Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L. donovani. The main species in the New World (the Western Hemisphere) are either in the L. mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or the subgenus Viannia (L. [V.] braziliensis, L. [V.] guyanensis, L. [V.] panamensis, and L. [V.] peruviana). The Viannia subgenus is also referred to as the L. (V.) braziliensis species complex.

1.1 Systemic Therapy (Parenteral)

Preferred Regimen (1): Sodium stibogluconate 20 mg/kg IV/IM q24h for 10-20 days
Preferred Regimen (2): Meglumine antimoniate 20 mg/kg IV/IM q24h for 10-20 days
Alternative Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days
Alternative Regimen (2): Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
Note: Data supporting the use of amphotericin B for treatment of cutaneous and mucosal leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.

1.2 Systemic Therapy (Oral)

1.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg

Preferred Regimen:Miltefosine 50 mg PO q12h for 28 days

1.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg

Preferred Regimen:Miltefosine 50 mg PO q8h for 28 days
Alternative Regimen (1): Ketoconazole 600 mg qd for 28 days OR qd for 6 weeks
Alternative Regimen (2): Fluconazole 200 mg qd for 6 weeks
Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved

1.3 Local Therapy

List of possible local therapies
Cryotherapy (with liquid nitrogen OR Thermotherapy (use of localized current field radiofrequency heat) OR Intralesional administration of SbV OR Topical application of Paromomycin (such as an ointment containing 15% Paromomycin/12% methylbenzethonium chloride in soft white paraffin)

2. Visceral Leishmaniasis

Visceral leishmaniasis usually is caused by the species L. donovani and L. infantum (L. chagasi generally is considered synonymous with L. infantum)

2.1 Systemic Therapy (Parenteral)

Preferred Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg)
Preferred Regimen (2): Sodium stibogluconate 20 mg/kg IV/IM q24h for 28 days
Preferred Regimen (3): Meglumine antimoniate 20 mg/kg IV/IM q24h for 28 days
Alternative Regimen: Amphotericin B deoxycholate 0.5-1 mg/kg IV q24h (Total dose: 15-20 mg/kg)
Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)

2.2 Systemic Therapy (Oral)

2.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg

Preferred Regimen: Miltefosine 50 mg PO q12h for 28 days

2.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg

Preferred Regimen: Miltefosine 50 mg PO q8h for 28 days

Plasmodium

Plasmodium Return to Top

1. Plasmodium falciparum^[281]

1.1 Treatment of uncomplicated P. falciparum malaria

1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)

Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days.

Note: The first two doses should, ideally, be given 8 h apart.
Dosage regimen based on Body weight (kg)
Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days

Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days

Note: A total therapeutic dose range of 6–30 mg/kg/day artesunate and 22.5–45 mg/kg/day per dose amodiaquine is recommended.
Dosage regimen based on Body weight (kg)
Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days

Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days

Dosage regimen based on Body weight (kg)
Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days

Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1

Dosage regimen based on Body weight (kg)
Body weight (kg)-5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
Body weight (kg)-10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
Body weight (kg)-25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1

Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days

Dosage regimen based on Body weight (kg)
Body weight (kg)-5 to < 8- Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
Body weight (kg)-8 to < 11- Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
Body weight (kg)-11 to < 17 - Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
Body weight (kg)-17 to < 25- Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
Body weight (kg)-25 to < 36- Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
Body weight (kg)-36 to < 60- Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
Body weight (kg)-60 < 80 - Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
Body weight (kg)- >80- Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days

1.1.2 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

Preferred regimen: Single dose of 0.25 mg/kg Primaquine with ACT

1.2 Recurrent Falciparum Malaria

1.2.1 Failure within 28 days

Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.

1.2.2 Failure after 28 days

Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.

1.3 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

Note: Single dose of 0.25 mg/kg bw Primaquine with ACT

1.4 Treating uncomplicated P. falciparum malaria in special risk groups

1.4.1 Pregnancy

First trimester of pregnancy : Quinine AND Clindamycin 10mg/kg/day PO bid for 7 days
Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
Note (2): Primaquine and tetracyclines should not be used in pregnancy.

1.4.2 Infants less than 5kg body weight : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
1.4.3 Patients co-infected with HIV: should avoid Artesunate + SP if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving efavirenz or zidovudine.
1.4.4 Large and Obese adults: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
1.4.5 Patients co-infected with TB: Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
1.4.6 Non-immune travellers : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
1.4.7 Uncomplicated hyperparasitaemia: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.

2. Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi

2.1 Blood Stage infection

2.1.1. Uncomplicated malaria caused by P. vivax

2.1.1.1 In areas with chloroquine-sensitive P. vivax

Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day.

2.1.1.2 In areas with chloroquine-resistant P. vivax

Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate + Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin + Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether + Lumefantrine, Artesunate + Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.

2.1.2 Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria

Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.

2.1.3 Mixed malaria infections

Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.

2.2 Liver stages (hypnozoites) of P. vivax and P. ovale

Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]

2.2.1 Primaquine for preventive relapse

Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days

2.2.2 Primaquine and glucose-6-phosphate dehydrogenase deficiency

Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks.
Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.

2.2.3 Prevention of relapse in pregnant or lacating women and infants

Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient).

3. Treatment of severe malaria

3.1 Treatment of severe falciparum infection with Artesunate

3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-

Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).

3.1.2 Young children weighing < 20 kg

Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
Alternatives regimen: use Artemether in preference to quinine for treating children and adults with severe malaria

3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)

3.2.1 Adults and children

Preferred regimen: Artesunate IM q24h
Alternative regimen: Artemether IM OR Quinine IM

3.2.2 Children < 6 years

Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
Note: Do not use rectal artesunate in older children and adults.

3.3 Pregancy

Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.

3.4 Treatment of severe P. Vivax infection

Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery.

3.5 Additional aspects of management in severe malaria

Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
Blood Transfusion :In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.

Toxoplasma gondii

Toxoplasma gondii Return to Top

Toxoplasma gondii (treatment)

1. Lymphadenopathic toxoplasmosis^[282]

Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.

2. Ocular disease^[283]

2.1 Adults

Preferred regimen: Pyrimethamine 100 mg PO for 1 day as a loading dose, then 25 to 50 mg/day AND Sulfadiazine 1 g PO qid AND folinic acid (Leucovorin 5-25 mg PO with each dose of Pyrimethamine

2.2 Pediatric

Preferred regimen: Pyrimethamine 2 mg/kg PO first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg PO bid AND folinic acid (Leucovorin 7.5 mg/day PO ) for 4 to 6 weeks followed by reevaluation of the patient's condition
Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.

3. Maternal and fetal infection^[284]

3.1 First and early second trimesters

Preferred regimen: Spiramycin is recommended

3.2 Late second and third trimesters

Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.

3.3 Infant

Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine, Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.

4. Toxoplasma gondii Encephalitis in AIDS^[285]

4.1 Treatment for acute infection

4.1.1 Patients with weight <60 kg
Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 50 mg PO qd AND Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO qd,
4.1.2 Patients with weight ≥60 kg

Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO qd and Leucovorin dose can be increased to 50 mg qd or bid
Alternative regimen (1): Pyrimethamine AND Leucovorin AND Clindamycin 600 mg IV/ PO q6h
Alternative regimen (2): TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO bid
Alternative regimen (3): Atovaquone 1500 mg PO bid AND Pyrimethamine AND Leucovorin
Alternative regimen (4): Atovaquone1500 mg PO bid AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
Alternative regimen (5): Atovaquone 1500 mg PO bid
Alternative regimen (6): Pyrimethamine AND Leucovorin AND Azithromycin 900–1200 mg PO qd
Note: Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

4.2 Chronic maintenance therapy

Preferred regimen: Pyrimethamine 25–50 mg PO qd AND sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO qd
Alternative regimen (2): TMP-SMX DS 1 tablet bid
Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
Alternative regimen (4): Atovaquone 750–1500 mg PO bid
Alternative regimen (5): Sulfadiazine 2000–4000 mg PO bid/qid
Alternative regimen (6): Atovaquone 750–1500 mg PO bid Pyrimethamine and Leucovorin doses are the same as for preferred therapy
Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.

Toxoplasma gondii (prophylaxis)

1. Prophylaxis to prevent first episode of encephalitis in AIDS^[286]

1.1 Indications

Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.

1.2 Prophylactic therapy

Preferred regimen: TMP-SMX 1 DS PO daily
Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
Alternative regimen (2): TMP-SMX 1 SS PO qd
Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (5): Atovaquone 1500 mg PO qd
Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd

Trichomonas vaginalis

Trichomonas vaginalis Return to Top

1. T. vaginalis infection in adults ^[287]

Preferred regimen (1): Metronidazole 2 g PO in a single dose
Preferred regimen (2): Tinidazole 2 g PO in a single dose
Alternative regimen: Metronidazole 500 mg PO bid for 7 days

2. T. vaginalis infection in pregnant and lactating Women

2.1 Pregnant women

Preferred regimen: Metronidazole 2 g PO in a single dose.

2.2 Post-partum and Breastfeeding

Preferred regimen (1): Metronidazole 2 g PO in a single dose.
Preferred regimen (2): Tinidazole 2 g PO in a single dose
Note (1): Do not breastfeed for 12-24 hrs following Metronidazole and 72 hrs following Tinidazole
Note (2): Symptomatic pregnant women, regardless of pregnancy stage, should be tested and considered for treatment. Pregnant women should be advised of the risk and benefits to treatment as infection (definitely) and treatment (possibly)
Note (3): Pregnant women with HIV who are treated for T. vaginalis infection should be retested 3 months after treatment.

3. T. vaginalis infection in patients with HIV

Preferred regimen: Metronidazole 500 mg PO bid for 7 days

4. Persistent or recurrent trichomoniasis

4.1 Treatment failure

Preferred regimen: Metronidazole 500 mg PO bid for 7 days

4.2 Treatment failure again

Preferred regimen (1): Metronidazole 2 g PO for 7 days
Preferred regimen (2): Tinidazole 2 g PO for 7 days

4.3 Nitroimidazole-resistant cases

Preferred regimen: Tinidazole 2-3 g PO for 14 days

African trypanosomiasis

African trypanosomiasis Return to Top

Sleeping sickness^[288]

1. East african trypanosomiasis

1.1 T. b. rhodesiense, hemolymphatic stage

1.1.1 Adult

Preferred regimen: Suramin 1 gm IV on days 1,3,5,14, and 21

1.1.2 Pediatric

Preferred regimen: Suramin 20 mg/kg IV on days 1, 3, 5, 14, and 21

1.2 T. b. rhodesiense, CNS involvement

1.2.1 Adult

Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.

1.2.2 Pediatric

Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days

2. West african trypanosomiasis

2.1 T. b. gambiense, hemolymphatic stage

2.1.1 Adult

Preferred regimen: Pentamidine 4 mg/kg/day IM/ IV for 7-10 days

2.1.2 Pediatric

Preferred regimen: Pentamidine 4 mg/kg/day IM/IV for 7-10 days
Note (1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

2.2 T. b. gambiense, CNS involvement

2.2.1 Adult

Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days

2.2.2 Pediatric

Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
Note (1): Eflornithine should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
Note (2): The safety of Eflornithine in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. Eflornithine is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.

American trypanosomiasis

American trypanosomiasis Return to Top

Chagas disease^[289]

1. Preferred regimen(1):

Patients of age < 12 years- Benznidazole 5-7.5 mg/kg/ day PO bid for 60 days
Patients of age 12 years or older- Benznidazole 5-7 mg/kg/day PO bid for 60 days

2. Preferred regimen(2):

Patients of age ≤ 10 years- Nifurtimox 15-20 mg/kg/day PO tid/ qid for 90 days
Patients of age 11-16 years- Nifurtimox 12.5-15 mg/kg/day PO tid/ qid for 90 days
Patients of age 17 years or older- Nifurtimox 8-10 mg/kg/day PO tid/ qid for 90 days

Note: In the United States, Nifurtimox and Benznidazole are not FDA approved and are available only from CDC under investigational protocols.

Parasites – Intestinal Nematodes (Roundworms)

Gnathostoma spinigerum Return to Top

Eosinophilic Meningitis
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.^[290]
Cutaneous disease:

Preferred regimen: Albendazole 400 mg bid for 21 days OR Ivermectin 200 mcg/kg qd for 2 days^[291]
Alternative regimen: Albendazole 400 mg qd for 21 days OR Ivermectin 200 mcg/kg qd single dose^[292]

Ancylostoma braziliense Return to Top

Preferred regimen^[293]

Adult: Albendazole 400 mg PO qd for 3 to 7 days
Pediatric: Albendazole > 2 years 400 mg PO qd for 3 days
Note: This drug is contraindicated in children younger than 2 years age

Alternative regimen^[294]

Adult: Ivermectin 200 mcg/kg PO qd for one or two days
Pediatric: Ivermectin >15 kg give 200 mcg/kg single dose

Angiostrongylus cantonensis Return to Top

Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60 mg qd for 2 weeks) and analgesics.^[295]
Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.^[296]

Ascaris lumbricoides Return to Top

Preferred regimen: Albendazole 400 mg PO qd OR Mebendazole 500 mg PO qd or 100 mg bid for 3 days^[297]

Note: Albendazole dose for children of 1-2 years is 200 mg instead of 400 mg.

Alternative regimen (1): Ivermectin 150 to 200 µg/kg PO single dose^[298]
Alternative regimen (2): Nitazoxanide 500 mg bid for 3 days ^[299]
Alternative regimen (3): Levamisole 150 mg PO single dose
Note: Pediatric dose: 2.5 mg/kg single dose ^[300]
Alternative regimen (4): Pyrantel Pamoate 11 mg/kg single dose PO - maximum 1.0 g^[300]
Alternative regimen (5): Piperazine citrate 75 mg/kg qd for 2 days - maximum 3.5 g^[300]

Capillaria philippinensis Return to Top

1. Intestinal capillariasis^[301]^[302]^[303]

Preferred regimen: Albendazole 400 mg/day PO for 10-30 days
Alternative regimen: Mebendazole 200 mg PO bid for 20-30 days

Enterobius vermicularis Return to Top

Preferred regimen (1): Albendazole 400 mg PO single dose - repeat in 2 weeks^[304]
Preferred regimen (2): Mebendazole 100 mg PO single dose - repeat in 2 weeks
Alternative regimen (1): Ivermectin 200 µg/kg PO single dose - repeat in 10 days^[305]
Alternative regimen (2): Pyrantel pamoate 11 mg/kg up to 1.0 g PO single dose - repeat in 2 weeks^[306]

Necator americanus Return to Top

Preferred regimen: Albendazole 400 mg PO single dose^[307]
Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days^[308]

Ancylostoma duodenale Return to Top

Preferred regimen: Albendazole 400 mg PO single dose^[307]
Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days^[309]

Strongyloides stercoralis Return to Top

Preferred regimen: Ivermectin 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other^[310]
Alternative regimen: Albendazole 400 mg PO bid for 3-7 days^[311]

Trichuris trichiura Return to Top

Preferred regimen: Albendazole 400 mg PO qd for 3 days
Alternatie regimen (1): Mebendazole 100 mg PO bid for 3 days
Alternative regimen (2): Ivermectin 200 mcg/kg/day PO qd for 3 days^[312]

Parasites – Extraintestinal Nematodes (Roundworms)

Ancylostoma braziliense Return to Top

Preferred regimen^[313]

Adult: Albendazole 400mg PO qd for 3-7 days.
Pediatric: Albendazole > 2 years 400mg PO qd for 3 days
Note: This drug is contraindicated in children younger than 2 years.

Alternative regimen^[314]

Adult: Ivermectin 200 mcg/kg PO qd for one or two days.
Pediatric: Ivermectin >15 kg give 200mcg/kg single dose.

Angiostrongylus cantonensis Return to Top

Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60mg qd for 2 weeks) and analgesics^[315]
Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.^[296]

Filariasis Return to Top

Filariasis^[316]^[317]^[318]

1. Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, Brugia timori

Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12 days (single dose if patient will continue to live in endemic area or is younger than 9 years old)

2. Loa loa filariasis^[319]

2.1 Symptomatic loiasis with < 8,000 microfilariae/mL

Preferred regimen: Diethylcarbamazine 8–10 mg/kd/day PO tid for 21 days

2.2 Symptomatic loiasis, with < 8,000 microfilariae/mL and failed 2 rounds DEC

Preferred regimen: Albendazole 200 mg PO bid for 21 days

2.3 Symptomatic loiasis, with ≥ 8,000 microfilariae/ml to suppress microfilaremia prior to treatment with DEC

Preferred regimen: Albendazole 200 mg PO bid for 21 days

2.4 Symptomatic loiasis, with ≥ 8,000 microfilariae/mL

Preferred regimen: Apheresis followed by Diethylcarbamazine
Note: Apheresis should be performed at an institution with experience in using this therapeutic modality for loiasis.

3. River blindness (onchocerciasis) caused by Onchocerca volvulus

Preferred regimen: Ivermectin 150 μg/kg PO single dose, repeated every 6-12 mos until asymptomatic
Alternative regimen: Doxycycline 100 mg PO qd for 6 weeks, alone or followed by Ivermectin 150 μg/kg PO single dose
Note: Do NOT administer Diethylcarbamazine where onchocerciasis is endemic due to increased risk for severe local inflammation in patients with ocular microfilariae.

4. Mansonella ozzardi

Preferred regimen: Ivermectin 200 μg/kg PO single dose
Note: Endosymbiotic Wolbachia are essential to filarial growth, development, embryogenesis and survival and represent an additional target for therapy. Doxycycline 100–200 mg PO qd for 6–8 weeks results in loss of Wolbachia and decrease in both micro- and macrofilariae.

5. Mansonella perstans

Preferred regimen: Doxycycline 100–200 mg PO qd for 6–8 weeks

6. Mansonella streptocerca

Preferred regimen (1): Diethylcarbamazine 6 mg/kd/day PO tid for 12 days
Preferred regimen (2): Ivermectin 150 μg/kg PO single dose

7. Tropical pulmonary eosinophilia caused by Wuchereria bancrofti

Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12–21 days

Gnathostoma spinigerum Return to Top

Eosinophilic Meningitis
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.^[290]
Cutaneous disease:

Preferred regimen: Albendazole 400 mg bid for 21 days OR Ivermectin 200 mcg/kg once daily for 2 days^[320]
Alternative regimen: Albendazole 400 mg daily for 21 days OR Ivermectin 200 mcg/kg once daily for 1 day^[321]

Toxocariasis Return to Top

1.1 Visceral toxocariasis

Preferred regimen: Albendazole 400 mg PO bid for five days (both adult and pediatric dosage)
Alternative regimen: Mebendazole 100-200 mg PO bid for five days (both adult and pediatric dosage)
Note: Treatment is indicated for moderate-severe cases. Patients with mild symptoms of toxocariasis may not require anthelminthic therapy as symptoms are limited.^[322]

1.2 Ocular toxocariasis

Preferred regimen: Prednisone 0.5-1mg/kg/day PO q24h AND Albendazole 400mg PO bid for 2 to 4 weeks (pediatric dose: 400mg PO qd)^[323]
Note: Surgical therapy might be neeeded.

Trichinella spiralis Return to Top

Trichinella spiralis^[324]

Preferred regimen (1): Albendazole 400 mg PO bid for 8-14 days
Preferred regimen (2): Mebendazole 200-400 mg PO tid for 3 days THEN 400-500 mg PO tid for 10 days
Note (1): Both treatment schemes are suitable for adult and pediatric dosages
Note (1): Albendazole and Mebendazole are contraindicated during pregnancy and not recommended in children aged 2 years.
Alternative regimen (1): (severe symptoms) Prednisone 30 mg/day-60 mg/day for 10-15 days
Alternative regimen (2): Pyrantel 10-20 mg/kg single dose for 2-3 days

Parasites – Trematodes (Flukes)

Clonorchis sinensis Return to Top

Preferred regimen: Praziquantel 75mg/kg/day PO tid for 2 days^[325]
Alternative regimen (1): Albendazole 10mg/kg/day PO qd for 7 days^[326]
Alternative regimen (2): Tribendimidine 400mg PO single dose^[327]
This regimen is still under investigation, but it appears to be as effective as Praziquantel.
Note: Urgent biliary decompression might be required for patients with acute cholangitis.

Dicrocoelium dendriticum Return to Top

Preferred regimen: Praziquantel 25 mg/kg PO tid for 2 days^[328]
Note: Praziquantel is not approved for treatment of children less than 4 years old.^[329]
Alternative regimen (1): Myrrh (commiphora molmol) 12 mg/kg/day PO for 6 days^[330]
Alternative regimen (2): Triclabendazole 10 mg/kg PO single dose^[330]

Fasciola hepatica Return to Top

Preferred regimen: Triclabendazole 10 mg/kg PO one dose^[331]
Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
Alternative regimen: Nitazoxanide 500mg PO bid for 7 days

Paragonimus westermani Return to Top

Preferred regimen (1): Praziquantel 25 mg/kg PO tid for 3 days^[332]
Preferred regimen (2): Triclabendazole 10 mg/kg PO qd or bid
Alternative regimen (1): Bithinol 30-50mg/kg PO on alternate days for 10-15 doses
Alternative regimen (2): Niclosamide 2mg/kg PO single dose

Schistosomiasis Return to Top

1. Schistosoma mansoni, S. haematobium, S. intercalatum^[333]

Preferred regimen: Praziquantel 40 mg/kg per day PO in qd or bid for one day
Alternative regimen (1): Oxamniquine 20 mg/kg PO single dose^[334]^[335]
Alternative regimen (2): Artemisinin no dose is established yet^[333]
Alternative regimen (3): Mefloquine 250 mg PO single dose
Note: There is no benefit in associating the alternative therapies to Praziquantel.
Note: Praziquantel is not effective against larval/egg stages of the disease.^[199]

2. S. japonicum, S. mekongi^[333]

Preferred regimen: Praziquantel 60 mg/kg per day PO bid for one day
Alternative regimen (1): Artemisinin no dose is established yet
Alternative regimen (2): Mefloquine 250 mg PO single dose
Note: There is no benefit in associating the alternative therapies to Praziquantel.

3. Katayama Fever

Preferred regimen: Prednisone 20-40 mg/day PO for 5 days, THEN Praziquantel^[336]
Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.^[337]

4. Neuroschistosomiasis

Preferred regimen: prednisone 1-2 mg/kg
Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.

Parasites – Cestodes (Tapeworms)

Echinococcus Return to Top
Echinococcus treatment^[338]

1.1 Echinococcus granulosus (hydatid disease) treatment^[339]

Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 10-15 mg/kg/day PO bid with meals for 3-6 months
Alternative regimen: Mebendazole 40-50mg/kg/day PO tid for 3-6 months
Note: Percutaneous aspiration-injection-reaspiration (PAIR). Puncture & needle aspirate cyst content. Instill hypertonic saline (15–30%) or absolute alcohol, wait 20–30 min, then re-aspirate with final irrigation. Administer Albendazole at least 4 hours before PAIR.
Note: If surgery is needed, make sure to administer Albendazole for at least a week before the surgery, and to keep the medication for at least 4 weeks after the procedure.

1.2 Echinococcus multilocularis (alveolar cyst disease) treatment^[340]

Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 15 mg/kg/day PO bid with meals for at least 2 years. Long-term follow up needed to evaluate progression of the lesions.

Note: Wide surgical resection only reliable treatment; technique evolving.

Neurocysticercosis

Neurocysticercosis Return to Top

Neurocysticercosis treatment

1. Parenchymal neurocysticercosis

1.1 Single lesions^[341]

Preferred regimen: Albendazole 15 mg/kg/day PO bid for 3-8 days AND Prednisone 1 mg/kg/day PO qid for 8-10 days followed by a taper

1.2 Multiple cysts

Preferred regimen: Albendazole 15 mg/kg/day PO bid for 8-15 days and high-dose steroids
Preferred regimen: Praziquantel 50 mg/kg/day PO tid AND Albendazole 15 mg/kg/day PO bid

1.3 Cysticercal encephalitis ^[341]

Cysticercal encephalitis (diffuse cerebral edema associated with multiple inflamed cysticerci) is a contraindication for antiparasitic therapy, since enhanced parasite killing can exacerbate host inflammatory response and lead to diffuse cerebral edema and potential transtentorial herniation. Most cases of cysticercal encephalitis improve with corticosteroid therapy

1.4 Calcified cysts

Radiographic evidence of parenchymal calcifications is a significant risk factor for recurrent seizure activity; these lesions are present in about 10 percent of individuals in regions where neurocysticercosis is endemic. Seizures in these patients should be treated with antiepileptic therapy.

2. Extraparenchymal NCC

2.1 Subarachnoid cysts

Preferred regimen: Albendazole 15 mg/kg/day PO bid for 28 days AND (Prednisone up to 60 mg/day PO OR Dexamethasone (up to 24 mg/day)) along with the antiparasitic therapy. The dose can often be tapered after a few weeks. However, in cases for which more prolonged steroid therapy is required, methotrexate can be used as a steroid-sparing agent

2.2 Giant cysts

Giant cysticerci are usually accompanied by cerebral edema and mass effect, which should be managed with high-dose corticosteroids (with or without mannitol).

2.3 Intraventricular cysts

Emergent management with CSF diversion via a ventriculostomy or placement of a ventriculo-peritoneal shunt
Treatment of residual hydrocephalus may be managed with endoscopic foraminotomy and endoscopic third ventriculostomy; this approach may also allow debulking of cisternal cysticerci

2.4 Ocular cysticercosis

Surgical excision is warranted in the setting of intraocular cysts
Cysticercal involvement of the extraocular muscles should be managed with albendazole and corticosteroids.

2.5 Spinal cysticercosis

Medical therapy with corticosteroids and antiparasitic drugs

Sparganosis Return to Top

Sparganosis (Spirometra mansonoides) treatment ^[342]

Preferred treatment: Surgical resection or ethanol injection of subcutaneous masses
Note: Praziquantel 75 mg/kg/day PO qd for 3 days is controversial. It's been innefective in some cases, but has had some results in patients when surgical therapy wasn't an option.^[343]

Parasites – Ectoparasites

Body lice Return to Top

Pediculus humanus, corporis treatment^[344]

A body lice infestation is treated by improving the personal hygiene of the infested person, including assuring a regular (at least weekly) change of clean clothes.
Clothing, bedding, and towels used by the infested person should be laundered using hot water (at least 130°F) and machine dried using the hot cycle.
Sometimes the infested person also is treated with a pediculicide Ivermectin Lotion; however, a pediculicide Ivermectin generally is not necessary if hygiene is maintained and items are laundered appropriately at least once a week. A pediculicide Ivermectin should be applied exactly as directed on the bottle or by your physician.

Head lice Return to Top

Pediculus humanus, capitis treatment^[345]

Preferred regimen (1): Permethrin 1% lotion apply to shampooed dried hair for 10 min.; repeat in 9-10 days
Preferred regimen (2): Malathion 0.5% lotion (Ovide) apply to dry hair for 8–12hrs, then shampoo (2 doses 7-9 days apart)
Alternative regimen: Ivermectin 200 μg/kg PO once; 3 doses at 7 day intervals reported effective.

Pubic lice Return to Top

Phthirus pubis treatment^[346]

Preferred regimen (1): Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes
Preferred regimen (2): Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
Alternative regimen (1): Malathion 0.5% lotion applied to affected areas and washed off after 8–12 hours
Alternative regimen (2): Ivermectin 250 ug/kg PO, repeated in 2 weeks

Myiasis Return to Top

Preferred regimen: No medications approved by the FDA are available for treatment^[347]
Note: Fly larvae need to be surgically removed.

Fly larvae treatment ^[348]
Preferred treatment (1): Occlude punctum to prevent gas exchange with petrolatum, fingernail polish, makeup cream or bacon.
Preferred treatment (2): When larva migrates, manually remove.
Note (1): Myiasis is due to larvae of flies.
Note (2): Usually cutaneous/subcutaneous nodule with central punctum.

Scabies Return to Top

Sarcoptes scabiei treatment^[349]

1. Adult

Preferred regimen (1): Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
Preferred regimen (2): Ivermectin 200 ug/kg PO qd and repeated in 2 weeks
Alternative regimen: Lindane (1%) 1 oz of lotion or 30 g of cream applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours

2. Infants and young children

Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
Note: Infants and young children aged< 10 years should not be treated with lindane.

3. Crusted Scabies

Crusted scabies (i.e., Norwegian scabies) is an aggressive infestation that usually occurs in immunodeficient, debilitated, or malnourished persons, including persons receiving systemic or potent topical glucocorticoids, organ transplant recipients, persons with HIV infection or human T-lymphotrophic virus-1-infection, and persons with hematologic malignancies.

Preferred regimen: (Topical scabicide 5% topical Benzyl benzoate 5% OR topical Permethrin 5% cream (full-body application to be repeated daily for 7 days then twice weekly until discharge or cure) AND treatment with Ivermectin 200 ug/kg PO on days 1,2,8,9, and 15. Additional Ivermectin treatment on days 22 and 29 might be required for severe cases

4.Pregnant or Lactating Women

Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours

Viruses

Adenovirus Return to Top

Adenovirus^[350]

1. In severe cases of pneumonia or post hematopoietic stem cell transplantation

Preferred regimen (1): Cidofovir 5 mg/kg/week IV for 2 weeks, then every 2 weeks AND Probenecid 1.25 g/M² PO given 3 hours before Cidofovir and 3 & 9 hours after each infusion
Preferred regimen (2): Cidofovir 1 mg/kg IV 3 times per week
Note: Ganciclovir, Foscarnet and Ribavirin are not recommended for use on adenovirus infection.^[351]

2. For hemorrhagic cystitis

Preferred regimen: Cidofovir (5 mg/kg in 100 mL saline instilled into bladder) intravesical^[352]

3. Pink eye (viral conjunctivitis)

Preferred regimen: No specific treatment available. If symptomatic, cold artificial tears may help.

4.Bronchitis

Preferred regimen: No specific therapy recommended, treatment is symptomatic.

SARS Return to Top

Severe acute respiratory distress syndrome- coronavirus^[353]^[354]^[355]
Preferred regimen: supportive therapy
Note: New therapies were studied for SARS during the last outbreaks which concluded:

Ribavirin ineffective and probably harmful due to haemolytic anaemia
Lopinavir PLUS Ritonavir is still controversial and need further investigation
Interferon has no benefit and its studies are inconclusive
Corticosteroids increases risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
Inhaled Nitric oxide potent mediator of airway inflammation, its has improved oxygenation in some studies

Cytomegalovirus Return to Top

Cytomegalovirus treatment^[356]

1. Immunocompetent patients

1.1 Mononucleosis syndrome

Preferred regimen: supportive therapy

1.2 CMV in pregnancy

Preferred regimen: Hyperimmune 200 IU/kg of maternal weight as single-dose during pregnancy

2. Immunocompromised patients

2.1 Retinitis

Preferred regimen (1): Ganciclovir intraocular implant PLUS Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900mg PO qq for maintenance therapy - for immediate sight-threatening lesions
Preferred regimen (2): Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900 mg PO qq for maintenance therapy - for peripheral lesions
Alternative regimen (1): Foscarnet 60 mg/kg IV q8h OR Foscarnet 90 mg/kg IV q12h for 14-21 days THEN Foscarnet 90-120 mg/kg IV q24h
Alternative regimen (2): Cidofovir 5 mg/kg IV for 2 weeks THEN Cidofovir 5 mg/kg IV every other week - each dose should be admnistered with IV saline hydration and probenecid
Alternative regimen (3): Ganciclovir 5 mg/kg IV q12h for 14-21 days THEN Valganciclovir 900 mg PO bid
Alternative regimen (4): Fomivirsen intravitreal injection - for relapses
Note: keep a maintenance dose of Valganciclovir 900 mg PO qd until CD4 >100/mm³

2.2 Transplant patients

Preferred regimen: Valganciclovir 900 mg PO bid OR Ganciclovir 5 mg/kg IV q12h for at least 2-3 weeek
Note: Use Valganciclovir 900 mg PO qd for 1-3 months if high dose of immunosuppression.

2.3 Colitis, esophagitis, gastritis

Preferred regimen: Ganciclovir 5 mg/kg/dose IV q12h for 3-6 weeks weeks for induction. There is no agreement on the use of maintenance.
Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
Note: Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.

2.4 Pneumonia

Preferred regimen: Valganciclovir 900 mg PO bid for 14–21 days, then 900 mg PO qd for maintenance therapy
Alternative regimen for retinitis: Ganciclovir 5 mg/kg IV q12h for 14–21 days, then Valganciclovir 900 mg PO qd
Note: In bone marrow transplant patients, combine therapy with CMV immune globulin.

2.5 Encephalitis, ventriculitis

Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking Ganciclovir as suppressive therapy.

2.6 Lumbosacral polyradiculopathy

Preferred regimen: Ganciclovir, as with retinitis
Alternative regimen: Foscarnet 40 mg/kg IV q12h another option
Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
Note (1): Switch to Valganciclovir when possible.
Note (2): Suppression continued until CD4 remains >100/mm³ for 6 months.

2.7 Peri/postnatal severe CMV infection in very low birth weight infants

Preferred regimen: Ganciclovir 6 mg/kg/dose IV q12h for 3 weeks^[357]

Enterovirus D68 Return to Top

Enterovirus treatment^[358]

Preferred regimen: supportive therapy
Note: A new drug Pleconaril designed to affect Rhinovirus is being suggested to be effective against Enterovirus D68 but further investigation is required^[359]

Ebola virus Return to Top

Ebola virus treatment^[360]^[361]

Preferred regimen: supportive therapy. There is no specific antiviral drug available for Ebola thus far. For information of investigational therapies including Favipiravir, Brincidofovir, ZMapp, TKM-Ebola, AVI-6002, and BCX4430, see here.

Isolate patient
Provide intravenous fluids (IV) (patients need large volumes in some cases) and maintain electrolytes at normal levels
Maintain oxygen saturation and blood pressure
Administer blood products if coagulopathy or bleeding, antiemetics if vomiting , antipyretics if fever, analgesics, anti-motility if severe diarrhea, total parenteral nutrition if patient has poor oral intake and dialysis if there's renal failure
Treat other infections if they occur. Provide adequate Gram-negative coverage and gram-positive if the patient has any catheter or hospital-acquired pneumonia.
If there's respiratory failure, invasive mechanical ventilation may be the best option to offer respiratory support

Note (1): Recovery from Ebola depends on good supportive care and the patient’s immune response.
Note (2): While there is no proven treatment available for Ebola virus disease, human convalescent whole blood has been used as an empirical treatment with promising results in a small group of EVD cases.^[362]^[363]
Note (3): People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.
Note (4): Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.

Marburg virus Return to Top

Marburg virus treatment

Preferred regimen: supportive therapy including maintenance of blood volume and electrolyte balance, as well as analgesics and standard nursing care^[364]^[365]

Hantavirus Return to Top

Hantavirus cardiopulmonary syndrome treatment^[366]

Preferred regimen: Supportive therapy, there is no specific treatment for hantavirus cardiopulmonary syndrome
Note (1): ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed
Note (2): Fluids should be administered carefully due to the potential for capillary leakage
Note (3): Supplemental oxygen should be administered if patients become hypoxic
Note (4): Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous
Note (5): Extracorporeal membrane oxygenation was used with survival rates of 50% in some studies in patients with cardiac index output <2.5L/min/m²^[367]

Dengue virus Return to Top

Dengue virus ^[368]

1. Patients who may be sent home

These are patients who are able to tolerate adequate volumes of oral fluids and pass urine at least once every six hours, and do not have any of the warning signs, particularly when fever subsides
Patients who are sent home should be monitored daily by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts

2. Ambulatory patients with stable haematocrit can be sent home

Encourage oral intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting
Give Paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours. Tepid sponge if the patient still has high fever
Should be brought to hospital immediately if any of the following occur: no clinical improvement, deterioration around the time of defervescence, severe abdominal pain, persistent vomiting, cold and clammy extremities, lethargy or irritability/restlessness, bleeding (e.g. black stools or coffee-ground vomiting), not passing urine for more than 4–6 hours

3. Patients who should be referred for in-hospital management

Patients may need to be admitted to a secondary health care centre for close observation, particularly as they approach the critical phase. These include patients with warning signs (Abdominal pain or tenderness, Persistent vomiting, Clinical fluid accumulation, Mucosal bleed, Lethargy, restlessness, Liver enlargment >2cm, Laboratory:increase in HCT concurrent with rapid decrease in platelet count), those with co-existing conditions that may make dengue or its management more complicated (such as pregnancy, infancy, old age, obesity, diabetes mellitus, renal failure, chronic haemolytic diseases), and those with certain social circumstances (such as living alone, or living far from a health facility without reliable means of transport)

3.1 With warning signs

Obtain a reference haematocrit before fluid therapy. Give only isotonic solutions such as 0.9% saline, Ringer’s lactate, or Hartmann’s solution. Start with 5–7 ml/ kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response
Reassess the clinical status and repeat the haematocrit. If the haematocrit remains the same or rises only minimally, continue with the same rate (2–3 ml/kg/hr) for another 2–4 hours. If the vital signs are worsening and haematocrit is rising rapidly, increase the rate to 5–10 ml/kg/hour for 1–2 hours. Reassess the clinical status, repeat the haematocrit and review fluid infusion rates accordingly
Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Intravenous fluids are usually needed for only 24–48 hours. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by urine output and/or oral fluid intake that is/are adequate, or haematocrit decreasing below the baseline value in a stable patient
Patients with warning signs should be monitored by health care providers until the period of risk is over. A detailed fluid balance should be maintained. Parameters that should be monitored include vital signs and peripheral perfusion (1–4 hourly until the patient is out of the critical phase), urine output (4–6 hourly), haematocrit (before and after fluid replacement, then 6–12 hourly), blood glucose, and other organ functions (such as renal profile, liver profile, coagulation profile, as indicated)

3.2 Without warning signs

Encourage oral fluids. If not tolerated, start intravenous fluid therapy of 0.9% saline or Ringer’s lactate with or without dextrose at maintenance rate. For obese and overweight patients, use the ideal body weight for calculation of fluid infusion. Patients may be able to take oral fluids after a few hours of intravenous fluid therapy. Thus, it is necessary to revise the fluid infusion frequently. Give the minimum volume required to maintain good perfusion and urine output. Intravenous fluids are usually needed only for 24–48 hours
Patients should be monitored by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, haematocrit, and white blood cell and platelet counts. Other laboratory tests (such as liver and renal functions tests) can be done, depending on the clinical picture and the facilities of the hospital or health centre

4. Severe dengue

Severe dengue: Severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress; severe haemorrhages; severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis)
4.1 Treatment of shock

4.1.1 Compensated shock

Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5–10 ml/kg/hour over one hour. Then reassess the patient’s condition (vital signs, capillary refill time, haematocrit, urine output). The next steps depend on the situation
If the patient’s condition improves, intravenous fluids should be gradually reduced to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, then to 2–3 ml/kg/hr, and then further depending on haemodynamic status, which can be maintained for up to 24–48 hours
If vital signs are still unstable (i.e. shock persists), check the haematocrit after the first bolus. If the haematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20 ml/kg/hr for one hour. After this second bolus, if there is improvement, reduce the rate to 7–10 ml/ kg/hr for 1–2 hours, and then continue to reduce as above. If haematocrit decreases compared to the initial reference haematocrit (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible
Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours

4.1.2 Hypotensive shock

Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if available) at 20 ml/kg as a bolus given over 15 minutes to bring the patient out of shock as quickly as possible
If the patient’s condition improves, give a crystalloid/colloid infusion of 10 ml/kg/hr for one hour. Then continue with crystalloid infusion and gradually reduce to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, and then to 2–3 ml/kg/hr or less, which can be maintained for up to 24–48 hours
If vital signs are still unstable (i.e. shock persists), review the haematocrit obtained before the first bolus. If the haematocrit was low (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross- match and transfuse blood as soon as possible (see treatment for haemorrhagic complications)
If the haematocrit was high compared to the baseline value (if not available, use population baseline), change intravenous fluids to colloid solutions at 10–20 ml/kg as a second bolus over 30 minutes to one hour. After the second bolus, reassess the patient. If the condition improves, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above. If the condition is still unstable, repeat the haematocrit after the second bolus
If the haematocrit decreases compared to the previous value (<40% in children and adult females, less than 45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications). If the haematocrit increases compared to the previous value or remains very high ( more than 50%), continue colloid solutions at 10–20 ml/kg as a third bolus over one hour. After this dose, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above when the patient’s condition improves
Further boluses of fluids may need to be given during the next 24 hours. The rate and volume of each bolus infusion should be titrated to the clinical response. Patients with severe dengue should be admitted to the high-dependency or intensive care area

4.2 Treatment of haemorrhagic complications

Blood transfusion required

Give 5–10ml/kg of fresh-packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. It is important that fresh whole blood or fresh red cells are given. Oxygen delivery at tissue level is optimal with high levels of 2,3 di-phosphoglycerate (2,3 DPG). Stored blood loses 2,3 DPG, low levels of which impede the oxygen-releasing capacity of haemoglobin, resulting in functional tissue hypoxia. A good clinical response includes improving haemodynamic status and acid-base balance
Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in haematocrit after blood transfusion. There is little evidence to support the practice of transfusing platelet concentrates and/or fresh-frozen plasma for severe bleeding. It is being practised when massive bleeding can not be managed with just fresh whole blood/fresh-packed cells, but it may exacerbate the fluid overload
Great care should be taken when inserting a naso-gastric tube which may cause severe haemorrhage and may block the airway. A lubricated oro-gastric tube may minimize the trauma during insertion. Insertion of central venous catheters should be done with ultra-sound guidance or by a very experienced person

5. Treatment of complications and other areas of treatment

5.1 Fluid overload

Oxygen therapy should be given immediately
When the following signs are present, intravenous fluids should be discontinued or reduced to the minimum rate necessary to maintain euglycaemia

signs of cessation of plasma leakage; stable blood pressure, pulse and peripheral perfusion; haematocrit decreases in the presence of a good pulse volume; afebrile for more than 24–48 days (without the use of antipyretics); resolving bowel/abdominal symptoms; improving urine output

The management of fluid overload varies according to the phase of the disease and the patient’s haemodynamic status. If the patient has stable haemodynamic status and is out of the critical phase (more than 24–48 hours of defervescence), stop intravenous fluids but continue close monitoring. If necessary, give oral or intravenous furosemide 0.1–0.5 mg/kg/dose once or twice daily, or a continuous infusion of furosemide 0.1 mg/kg/hour. Monitor serum potassium and correct the ensuing hypokalaemia
If the patient has stable haemodynamic status but is still within the critical phase, reduce the intravenous fluid accordingly. Avoid diuretics during the plasma leakage phase because they may lead to intravascular volume depletion
Patients who remain in shock with low or normal haematocrit levels but show signs of fluid overload may have occult haemorrhage. Further infusion of large volumes of intravenous fluids will lead only to a poor outcome. Careful fresh whole blood transfusion should be initiated as soon as possible. If the patient remains in shock and the haematocrit is elevated, repeated small boluses of a colloid solution may help

5.2 Other complications of dengue

Both hyperglycaemia and hypoglycaemia may occur, even in the absence of diabetes mellitus and/or hypoglycaemic agents. Electrolyte and acid-base imbalances are also common observations in severe dengue and are probably related to gastrointestinal losses through vomiting and diarrhoea or to the use of hypotonic solutions for resuscitation and correction of dehydration. Hyponatraemia, hypokalaemia, hyperkalaemia, serum calcium imbalances and metabolic acidosis (sodium bicarbonate for metabolic acidosis is not recommended for pH ≥ 7.15) can occur. One should also be alert for co-infections and nosocomial infections.

5.3 Supportive care and adjuvant therapy

renal replacement therapy, with a preference to continuous veno-venous haemodialysis (CWH), since peritoneal dialysis has a risk of bleeding;
vasopressor and inotropic therapies as temporary measures to prevent life- threatening hypotension in dengue shock and during induction for intubation, while correction of intravascular volume is being vigorously carried out;
further treatment of organ impairment, such as severe hepatic involvement or encephalopathy or encephalitis;
further treatment of cardiac abnormalities, such as conduction abnormalities, may occur (the latter usually not requiring interventions)

West Nile virus Return to Top

West nile virus

1.1. Prevention

No WNV vaccines are licensed for use in humans. In the absence of a vaccine, prevention of WNV disease depends on community-level mosquito control programs to reduce vector densities, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.
Personal protective measures include use of mosquito repellents, wearing long-sleeved shirts and long pants, and limiting outdoor exposure from dusk to dawn. Using air conditioning, installing window and door screens, and reducing peridomestic mosquito breeding sites, can further decrease the risk for WNV exposure.
Blood and some organ donations in the United States are screened for WNV infection; health care professionals should remain vigilant for the possible transmission of WNV through blood transfusion or organ transplantation. Any suspected WNV infections temporally associated with blood transfusion or organ transplantation should be reported promptly to the appropriate state health department.

1.2. Treatment

There is no specific treatment for WNV disease; clinical management is supportive. Patients with severe meningeal symptoms often require pain control for headaches and antiemetic therapy and rehydration for associated nausea and vomiting. Patients with encephalitis require close monitoring for the development of elevated intracranial pressure and seizures. Patients with encephalitis or poliomyelitis should be monitored for inability to protect their airway. Acute neuromuscular respiratory failure may develop rapidly and prolonged ventilatory support may be required.

Yellow Fever Return to Top

Yellow fever^[369]^[370]

Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.

Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.

Chikungunya virus Return to Top

Chikungunya Fever ^[371]

Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.

Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.

Hepatitis A virus Return to Top

Preferred regimen: No therapy recommended. If within 2 wks of exposure, IVIG 0.02 mL per kg IM times 1 protective.

Hepatitis B virus Return to Top
Acute Hepatitis B

Chronic Hepatitis B

1. Patients with HBeAg-positive chronic hepatitis B^[372]

1.1. HBV DNA >20,000, ALT <2 times upper limit normal (ULN)^[372]

Observe; consider treatment when ALT becomes elevated.
Consider biopsy in persons 40 years, ALT persistently high normal >2 times upper limit normal (ULN), or with family history of HCC.
Consider treatment if HBV DNA >20,000 IU/mL and biopsy shows moderate/severe inflammation or significant fibrosis.

1.2. HBV DNA >20,000, ALT >2 times upper limit normal (ULN)^[372]

Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 48 weeks
Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
If creatinine clearance 30–49 give 300 mg q48 hrs
If creatinine clearance 10–29 give 300 mg q72-96 hrs
If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
If creatinine clearance <10 without dialysis there is no recommendation
Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 16 weeks
Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 100 mg PO qd
If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 10 mg PO daily
If creatinine clearance 30–49 give 10 mg PO every other day
If creatinine clearance 10–19 10 mg PO every third day
If hemodialysis patients give 10 mg PO every week following dialysis
Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion

Alternative regimen (4): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 600 mg PO once daily
If creatinine clearance 30–49 600 give mg PO once every 48 hours
If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

Note (1): duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
Note (2): Observe for 3-6 months and treat if no spontaneous HBeAg loss.
Note (3): Consider liver biopsy prior to treatment if compensated.
Note (4): Immediate treatment if icteric or clinical decompensation.
Note (5): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
Note (6): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
Note (7): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
Note (8): End-point of treatment – Seroconversion from HBeAg to anti-HBe.
Note (9): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).

1.3. Children with elevated ALT greater than 2 times normal^[372]

Preferred regimen(1): Interferon alpha (IFNα) 6 MU/m2 SC thrice weekly with a maximum of 10 MU
Preferred regimen(2): Lamivudine (LAM) 3 mg/kg/d PO with a maximum of 100 mg/d.

2. Patients with HBeAg-negative chronic hepatitis B^[372]

2.1. HBV DNA >2,000 IU/mL and elevated ALT >2 times normal

Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 1 year
Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
If creatinine clearance 30–49 give 300 mg q48 hrs
If creatinine clearance 10–29 give 300 mg q72-96 hrs
If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
If creatinine clearance <10 without dialysis there is no recommendation
Note: duration of treatment is more than 1 year

Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine
If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine
If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine
If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
Note: duration of treatment is more than 1 year

Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 1 year
Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 100 mg PO qd
If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
Note: duration of treatment is more than 1 year

Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 10 mg PO daily
If creatinine clearance 30–49 give 10 mg PO every other day
If creatinine clearance 10–19 10 mg PO every third day
If hemodialysis patients give 10 mg PO every week following dialysis
Note: duration of treatment is more than 1 year

Alternative regimen (4): Telbivudine (LdT)Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 600 mg PO once daily
If creatinine clearance 30–49 600 give mg PO once every 48 hours
If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

Note (1): duration of treatment is more than 1 year
Note (2): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
Note (3): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
Note (4): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
Note (5): End-point of treatment – not defined
Note (6): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).

3. HBV DNA >2,000 IU/mL and elevated ALT 1->2 times normal^[372]

Consider liver biopsy and treat if liver biopsy shows moderate/severe necroinflammation or significant fibrosis.

4. HBV DNA <2,000 IU/mL and ALT < upper limit normal (ULN)^[372]

Observe, treat if HBV DNA or ALT becomes higher.

5. +/- HBeAg and detectable HBV DNA with Cirrhosis^[372]

5.1. Compensated Cirrhosis and HBV DNA >2,000

Preferred regimen (1): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.

Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
If creatinine clearance 30–49 give 300 mg q48 hrs
If creatinine clearance 10–29 give 300 mg q72-96 hrs
If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
If creatinine clearance <10 without dialysis there is no recommendation

Alternative regimen (1): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 100 mg PO qd
If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.

Alternative regimen (2): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 10 mg PO daily
If creatinine clearance 30–49 give 10 mg PO every other day
If creatinine clearance 10–19 give 10 mg PO every third day
If hemodialysis patients give 10 mg PO every week following dialysis

Alternative regimen (3): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 600 mg PO once daily
If creatinine clearance 30–49 600 give mg PO once every 48 hours
If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

Note (1): LAM and LdT not preferred due to high rate of drug resistance.
Note (2): ADV not preferred due to weak antiviral activity and high risk of resistance after 1st year.
Note (3): These patients should receive long-term treatment. However, treatment may be stopped in HBeAg-positive patients if they have confirmed HBeAg seroconversion and have completed at least 6 months of consolidation therapy and in HBeAg-negative patients if they have confirmed HBsAg clearance.

5.2. Compensated Cirrhosis and HBV DNA <2,000

Consider treatment if ALT elevated.

5.3. Decompensated Cirrhosis

Preferred regimen (1): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
If creatinine clearance 30–49 give 300 mg q48 hrs
If creatinine clearance 10–29 give 300 mg q72-96 hrs
If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
If creatinine clearance <10 without dialysis there is no recommendation

Preferred regimen (2): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.

Preferred regimen (3): Lamivudine (LAM) AND Adefovir (ADV)

Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 100 mg PO qd
If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.

Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 10 mg PO daily
If creatinine clearance 30–49 give 10 mg PO every other day
If creatinine clearance 10–19 give 10 mg PO every third day
If hemodialysis patients give 10 mg PO every week following dialysis

Preferred regimen (4): Telbivudine (LdT) AND Adefovir (ADV)

Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 600 mg PO once daily
If creatinine clearance 30–49 600 give mg PO once every 48 hours
If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis

Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:

If creatinine clearance >50 or normal renal function give 10 mg PO daily
If creatinine clearance 30–49 give 10 mg PO every other day
If creatinine clearance 10–19 give 10 mg PO every third day
If hemodialysis patients give 10 mg PO every week following dialysis

Note: coordinate treatment with transplant center and refer for liver transplant.
Life-long treatment is recommended.

6. +/- HBeAg and undetectable HBV DNA with Cirrhosis^[372]

Compensated Cirrhosis: Observe
Uncompensated Cirrhosis: Refer for liver transplant

Hepatitis C virus Return to Top

Chronic Hepatitis C

1. Treatment regimens for chronic hepatitis C virus genotype 1^[373]

1.1. Treatment regimens for genotype 1a:

Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid AND weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) OR 24 weeks (cirrhosis)
Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
Note: these regimens are recommended for treatment-naive patients with HCV genotype 1a infection.

1.2. Treatment regimens for genotype 1b:

Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
Preferred regimen (2): Paritaprevir PO 150 mg qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid for 12 weeks. The addition of weight-based Ribavirin PO qd (1000 mg [<75kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis
Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
Note: these regimens are recommended for treatment-naive patients with HCV genotype 1b infection.

2. Treatment regimens for chronic hepatitis C virus genotype 2^[374]

Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
Note (1): This regimen are recommended for treatment-naive patients with HCV genotype 2 infection.
Note (2): Extending treatment to 16 weeks is recommended in patients with cirrhosis.

3. Treatment regimens for chronic hepatitis C virus genotype 3^[375]

Preferred regimen: Sofosbuvir 400 mg PO qd and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd for 24 weeks
Alternative regimen: Sofosbuvir 400 mg and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd AND weekly PEG-IFN for 12 weeks is an acceptable regimen for IFN-eligible, treatment-naive patients with HCV genotype 3 infection.
Note: These regimens are recommended for treatment-naive patients with HCV genotype 3 infection.

4. Treatment regimens for chronic hepatitis C virus genotype 4

Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
Preferred regimen (3): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
Alternative regimen (1): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks
Alternative regimen (2): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
Note: These regimens are accpetable for treatment-naive patients with HCV genotype 3 infection.

5. Treatment regimens for chronic hepatitis C virus genotype 5^[376]

Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd(1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is recommended for treatment-naive patients with HCV genotype 5 infection.
Alternative regimen: Weekly PEG-IFN AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 48 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 5 infection.

6. Treatment regimens for chronic hepatitis C virus genotype 6^[377]

Preferred regimen: Ledipasvir 90 mg PO qd AND Sofosbuvir PO qd 400 mg for 12 weeks is recommended for treatment-naive patients with HCV genotype 6 infection.
Alternative regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 6 infection.

Hepatitis D virus Return to Top
Preferred regimen: Interferon alpha(IFNα) 5 MU daily OR 9 MU three times a week for 6–12 months ^[378]

Hepatitis E virus Return to Top
Hepatitis E treatment^[379]

Preferred regimen: supportive therapy. There is no specific treatment available.

Note (1): Hepatitis E is usually self-limiting, hospitalization is generally not required.
Note (2): Hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.

Epstein-Barr virus Return to Top

Epstein-Barr Virus (EBV) ^[380]

There is no vaccine to protect against EBV infection. You can help protect yourself by not kissing or sharing drinks, food, or personal items, like toothbrushes, with people who have EBV infection.
There is no specific treatment for EBV. However, some things can be done to help relieve symptoms, including

drinking fluids to stay hydrated
getting plenty of rest
taking over-the-counter medications for pain and fever

Human herpesvirus 6 Return to Top

Human herpesvirus 6 treatment^[381]^[382]

Preferred regimen: supportive therapy
Note: If patient is immunocompromised, there are no antiviral regimens stablished as there are no clinical trials to validate their use on these cases. Consider administering Ganciclovir, Acyclovir, Foscarnet OR Cidofovir.^[383]^[382]

Roseola Return to Top

Human herpesvirus 7 (roseola virus) treatment

Preferred regimen: Supportive therapy
Note (1): Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management^[383]
Note (2): For HIV-positive patients, antiretroviral therapy may be advisable^[384]
Note (3): The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet^[385]^[383]

Human herpesvirus 8 (KSHV) Return to Top

1. Mild to moderate Kaposi sarcoma^[386]

Preferred regimen: initiate or optimize ART

2. Advanced Kaposi sarcoma (ACTG Stage T1, including disseminated cutaneous or visceral Kaposi sarcoma)

Preferred regimen: chemotherapy (per oncology consult) AND ART

3. Primary effusion lymphoma

Preferred regimen: chemotherapy (per oncology consult) AND ART
Note: Valganciclovir PO or Ganciclovir IV can be used as adjunctive therapy.

4. Multicentric Castleman's disease

Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
Preferred regimen (3): Valganciclovir 900 mg PO BID AND Zidovudine 600 mg PO q6h for 7–21 days
Alternative regimen: Rituximab 375 mg/m2 given weekly for 4–8 weeks (may be an alternative to or used adjunctively with antiviral therapy)

Herpes simplex virus Return to Top

Genital Herpes^[387]

1.First Clinical Episode of Genital Herpes

Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
Note:Treatment can be extended if healing is incomplete after 10 days of therapy.

2.Established HSV-2 Infection

2.1 Suppressive Therapy for Recurrent Genital Herpes

Preferred Regimen (1): Acyclovir 400 mg PO bid
Preferred Regimen (2): Valacyclovir 500 mg PO qd
Preferred Regimen (3): Valacyclovir 1 g PO qd
Preferred Regimen (4): Famciclovir 250 mg PO bid
Note(1):Daily therapy with Acyclovir for as long as 6 years and with Valacyclovir OR Famciclovir for 1 year
Note(2):Valacyclovir 500 mg qd might be less effective than other Valacyclovir OR Acyclovir dosing regimens in persons who have very frequent recurrences (i.e., ≥10 episodes per year).

2.2 Episodic Therapy for Recurrent Genital Herpes

Preferred Regimen (1): Acyclovir 400 mg PO tid for 5 days
Preferred Regimen (2): Acyclovir 800 mg PO bid for 5 days
Preferred Regimen (3): Acyclovir 800 mg PO tid for 2 days
Preferred Regimen (4): Valacyclovir 500 mg PO bid for 3 days
Preferred Regimen (5): Valacyclovir 1 g PO qd for 5 days
Preferred Regimen (6): Famciclovir 125 mg PO bid for 5 days
Preferred Regimen (7): Famciclovir 1 g PO bid for 1 day
Preferred Regimen (8): Famciclovir 500 mg once, followed by 250 mg PO bid for 2 days

3. Severe Disease (disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningoencephalitis).

Preferred Regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy. HSV encephalitis requires 21 days of intravenous therapy. Impaired renal function warrants an adjustment in acyclovir dosage.

4. Special Considerations

4.1 HIV Infection

4.1.1 Daily Suppressive Therapy in Persons with HIV

Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
Preferred Regimen (2): Valacyclovir 500 mg PO bid
Preferred Regimen (3): Famciclovir 500 mg PO bid

4.1.2 Episodic Infection in Persons with HIV

Preferred Regimen (1): Acyclovir 400 mg PO tid for 5–10 days
Preferred Regimen (2): Valacyclovir 1 g PO bid for 5–10 days
Preferred Regimen (3): Famciclovir 500 mg PO bid for 5–10 days
Note: For severe HSV disease, initiating therapy with Acyclovir 5–10 mg/kg IV q8 h might be necessary.

4.2 Genital Herpes in Pregnancy

Suppressive therapy of pregnant women with recurrent genital herpes
Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
Preferred Regimen (2): Valacyclovir 500 mg PO bid
Note:Treatment recommended starting at 36 weeks of gestation.

4.3 Neonatal Herpes

Known or suspected neonatal herpes

Preferred Regimen: Acyclovir 20 mg/kg IV q 8 h
Note (1): Treatment for 14 days if disease is limited to the skin and mucous membranes, or
Note (2): Treatment for 21 days for disseminated disease and that involving the central nervous system.

4.4 Acyclovir-resistant genital herpes

Preferred Regimens: Foscarnet 40–80 mg/kg IV q8 h until clinical resolution is attained
Alternative Regimen (1): Cidofovir 5 mg/kg IV once weekly might also be effective.
Alternative Regimen (2): Imiquimod topical preparations should be applied to the lesions qd for 5 consecutive days.

4.5 Management of Sex Partners

Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
Note:The sex partners of persons who have genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated

4.6 Allergy, Intolerance, and Adverse Reactions

Allergic and other adverse reactions to oral Acyclovir, Valacyclovir, and Famciclovir are rare. Desensitization to acyclovir has been described.

vzv

Varicella-zoster virus Return to Top

1. Varicella zoster treatment^[388]

1.1 Non Immunocompromised person

Preferred regimen (1): Acyclovir 500 mg PO five times a dayfor 7-10 days
Preferred regimen (2): Famciclovir 500 mg PO tid for 7 days
Preferred regimen (3): Valacyclovir 1 g PO tid for 7 days
Preferred regimen (4): Brivudin 125 mg PO qd for 7 days

1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications

Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
Preferred regimen (2): Foscarnet 40 mg/ kg IV q8h until lesions are healed
Note: Brivudin is not available in USA and has not been approved by FDA. Foscarnet is not approve by FDA

2. Treatment of VZV complications^[389]

2.1 VZV ophthalmicus

Treatment includes the following

(1) Famciclovir OR Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with Acyclovir IV given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences, AND Prednisone 20 mg PO tid for 4 days or bid for 6 days, and then qd for 4 day
(2) Bacitracin-Polymyxin ophthalmic ointment administered bid ,to protect the ocular surface;
(3) Topical Prednisolone 0.125%–1% 2–6 times daily prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis;
(4) Homatropine 5% bid as needed for iritis
(5) Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning)ocular pressure–lowering drugs given as needed for glaucoma
Note (1): Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit.
Note (2): pain medications and cool to tepid wet compresses (if tolerated) and no topical antivirals, because they are ineffective

2.2 VZV retinitis

Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks

3 Recommendations for treating varicella zoster virus (VZV) Infections in HIV-Infected adults and adolescents^[390]

3.1 Primary Varicella Infection (Chickenpox)

3.1.1 Uncomplicated Cases

Preferred regimen (1):Valacyclovir 1 g PO tid for 5–7 days
Preferred regimen (2): Famciclovir 500 mg PO tid for 5–7 days
Alternative regimen: Acyclovir 800 mg PO 5 times daily for 5–7 days

3.1.2 Severe or Complicated Cases

Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days
Note: May switch to oral Famciclovir, Valacyclovir, or Acyclovir after defervescence if no evidence of visceral involvement is evident

3.2 Herpes Zoster (Shingles)

3.2.1 Acute Localized Dermatomal

Preferred regimen (1): Valacyclovir 1000 mg PO tid for 7–10 days
Preferred regimen (2): Famciclovir 500 mg PO tid for 7–10 days
Alternative Therapy: Acyclovir 800 mg PO 5 times daily for 7–10 days
Note: Longer duration should be considered if lesions resolve slowly

3.2.2 Extensive Cutaneous Lesion or Visceral Involvement

Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident, then switch to (Valacyclovir 1 g PO tid, Famciclovir 500 mg PO tid, or Acyclovir 800 mg PO 5 times daily)—to complete a 10–14 day course, when formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving

3.3 PORN (Progressive outer retinal necrosis)

Preferred regimen: Ganciclovir 5 mg/kg and/or Foscarnet 90 mg/kg IV q12h AND Ganciclovir 2 mg/0.05mL and/or foscarnet 1.2 mg/0.05mL intravitreal twice weekly.
Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist and optimize ART regimen.
Note: Ganciclovir ocular implants are no longer commercially available

3.4 ARN (Acute retinal necrosis)

Preferred regimen: Acyclovir 10-15 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid for 6 weeks AND Ganciclovir 2 mg/0.05mL intravitreal qd/bid twice weekly
Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist

4 Prevention of varicella zoster virus (VZV) Infections in HIV-Infected Adults and Adolescents

4.1 Pre-Exposure Prevention of VZV Primary Infection

Indications

Adult and adolescent patients with CD4 count ≥200 cells/mm3 without documentation of vaccination, health-care provider diagnosis or verification of a history of varicella or herpes zoster, laboratory confirmation of disease, or persons who are seronegative for VZV. Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
Vaccination
Primary varicella vaccination (Varivax™), 2 doses (0.5 mL SQ) administered 3 months apart
If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended.
VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts.
If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
If post-exposure acyclovir has been administered, wait at least 3 days before varicella vaccine.

4.2 Post-Exposure Prophylaxis

Indication

Close contact with a person who has active varicella or herpes zoster, and
Is susceptible to VZV (i.e., has no history of vaccination or of either condition, or is known to be VZV seronegative)

Preferred regimen: VariZIG 125 IU /10 kg (maximum of 625 IU) IM, administered as soon as possible and within 10 days after exposure to a person with active varicella or herpes zoster
Alternative regimen (Begin 7–10 Days After Exposure): Acyclovir 800 mg PO 5 times/day for 5–7 days OR Valacyclovir 1 g PO tid for 5–7 days
If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
Note: Patients receiving monthly high dose IVIG (i.e., >400 mg/kg) are likely to be protected against VZV and probably do not require VariZIG if the last dose of IVIG was administered <3 weeks before VZV exposure.
Note: Neither these pre-emptive interventions nor post-exposure varicella vaccination have been studied in HIV-infected adults and adolescents.
If acyclovir or valacyclovir is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.

hpv

Human papillomavirus Return to Top

Anogenital Warts^[391]

1.Preferred regimen for External Anogenital Warts(i.e., penis, groin, scrotum, vulva, perineum, external anus, and perianus)

1.1 Patient-Applied: Imiquimod 3.75% or 5% cream OR Podofilox 0.5% solution or gel OR Sinecatechins 15% ointment
1.2 Provider-Administered: Cryotherapy with liquid nitrogen or cryoprobe OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, laser,or electrosurgery OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% solution
Note (1): Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution anoscopy.
Note (2): Might weaken condoms and vaginal diaphragms.

2.Alternative Regimens for External Genital Warts

2.1 Urethral Meatus Warts

Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal

2.2 Vaginal Warts

Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
Note: The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation

2.3 Cervical Warts

Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
Note: Management of cervical warts should include consultation with a specialist.For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated.

2.4 Intra-anal Warts

Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
Note: Management of intra-anal warts should include consultation with a specialist.

3. Specific considerations

3.1 Follow-up

Most anogenital warts respond within 3 months of therapy. Factors that might affect response to therapy include immunosuppression and treatment compliance. In general, warts located on moist surfaces or in intertriginous areas respond best to topical treatment. A new treatment modality should be selected when no substantial improvement is observed after a complete course of treatment or in the event of severe side effects; treatment response and therapy-associated side effects should be evaluated throughout the course of therapy.

3.2 Management of sex partners

Persons should inform current partner(s) about having genital warts because the types of HPV that cause warts can be passed on to partners. Partners should receive counseling messages that partners might already have HPV despite no visible signs of warts, so HPV testing of sex partners of persons with genital warts is not recommended.

3.3 Pregnancy

Podofilox (podophyllotoxin), Podophyllin, and Sinecatechins should not be used during pregnancy. Imiquimod appears to pose low risk but should be avoided until more data are available.
Cesarean delivery is indicated for women with anogenital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding.
Pregnant women with anogenital warts should be counseled concerning the low risk for warts on the larynx of their infants or children (recurrent respiratory papillomatosis).

3.4 HIV infection

Data do not support altered approaches to treatment for persons with HIV infection.
Squamous cell carcinomas arising in or resembling anogenital warts might occur more frequently among immunosuppressed persons, therefore requiring biopsy for confirmation of diagnosis for suspicious cases

3.5 High-grade squamous intraepithelial lesions

Biopsy of an atypical wart might reveal HSIL or cancer of the anogenital tract. In this instance, referral to a specialist for treatment is recommended.

influenza A& B

Influenza A & B Return to Top

Antiviral Medications Recommended for Treatment of Influenza

1. Adults

Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days
Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs

2. Children

2.1 Children < 1 yr

Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO bid for 5 days

2.2 Children > 1 yr

2.2.1 Children ≤ 15 kg

Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO bid for 5 days

2.2.2 Children > 15 to 23 kg

Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO bid for 5 days

2.2.3 Children > 23 to 40 kg

Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO bid for 5 days

2.2.4 Children > 40 kg

Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days, may be considered for children > 7 yrs old

3. Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis

3.1 Oseltamivir

Creatinine clearance 61 to 90 mL/min-75 mg PO bid for 5 days
Creatinine clearance 31 to 60 mL/min-30 mg PO bid for 5 days
Creatinine clearance 10 to 30 mL/min-30 mg PO qd for 5 days
ESRD Patients on Hemodialysis
Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange

3.2 Peramivir

Creatinine clearance >50 mL/min-600mg IV single dose
Creatinine clearance 30 to 49 mL/min-200mg IV single dose
Creatinine clearance 10 to 29 mL/min-100mg IV single dose
ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance
Note: No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment.

4. Antiviral Medications Recommended for Chemoprophylaxis of Influenza

4.1. Adults

Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7days
Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days

4.2. Children

4.2.1 Children < 1 yr

Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO qd for 7 days

4.2.2 Children > 1 yr

4.2.2.1 Children ≤ 15 kg

Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO qd for 7 days

4.2.2.2 Children > 15 to 23 kg

Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO qd for 7 days

4.2.2.3 Children > 23 to 40 kg

Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO qd for 7 days

4.2.2.4 Children > 40 kg

Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7 days
Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days, may be considered for children > 7 yrs older
Note: If child is < 3 months old, use of Oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group.

Avian influenza

Avian influenza Return to Top

1. Preferred regimen:Oseltamivir 75 mg PO qd for a minimum 10 days ^[392]^[393]

Note:Patients with severe disease may have diarrhea and may not absorb oseltamivir efficiently

2. Patients with Avian Influenza who have diarrhea and malabsorption

Preferred regimen (1): Zanamivir 10 mg inhaled bid for minimum 5 days
Preferred regimen (2): [[Peramivir] ]600 mg IV as a single dose for 1 day
Note(1): Preliminary evidence demonstrates that Neuraminidase inhibitor can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, one of the following 3 neuraminidase inhibitors should be administered as soon possible, preferably within 48 hours of symptom onset.
Note(2): The use of Corticosteroids is not recommended.
Note(3): Physicians may consider increasing either the recommended daily dose and/or the duration of treatment in cases of severe disease.
Note(4): The use of Amantadine is not recommended as most H5N1 and H7N9 avian influenza viruses are resistant to it.^[394]
Note(5): Supportive care is also an important cornerstone of the care of patients with avian influenza. Considering the severity of the illness and the possible complications, patients may require fluid resuscitation, vasopressors, intubation and ventilation, paracentesis, hemodialysis or hemofiltration, and parentral nutrition.

Swine influenza Return to Top

Swine influenza ^[395]

1. Condition1: Patients who have severe or progressive clinical illness

Preferred regimen: Oseltamivir 150 mg PO bid
Note (1): Treatment duration depends on clinical response
Note (2): Where the clinical course remains severe or progressive, despite 5 or more days of antiviral treatment, monitoring of virus replication and shedding, and antiviral drug susceptibility testing is desirable
Note (3): Antiviral treatment should be maintained without a break until virus infection is resolved or there is satisfactory clinical improvement
Note (4): Patients who have severe or progressive clinical illness, but who are unable to take oral medication may be treated with oseltamivir administered by nasogastric or orogastric tube

2. Condition2: In situations where oseltamivir is not available, or not possible to use, patients who have severe or progressive clinical illness

Preferred regimen: Zanamivir inhaled
Note: Zanamivir IV should be considered where available and is recommended for those with serious or progressive illness. If not available, Peramivir IV may be considered

3. Condition3: Severely immunosuppressed patients

Preferred regimen: Antiviral chemoprophylaxis by using Oseltamivir OR Zanamivir

Measles Return to Top

Measles

1.1. Prevention

1.1.1. Vaccines

Note (1): Measles can be prevented with measles-containing vaccine, which is primarily administered as the combination measles-mumps-rubella (MMR) vaccine. The combination measles-mumps-rubella-varicella (MMRV) vaccine can be used for children aged 12 months through 12 years for protection against measles, mumps, rubella and varicella. Single-antigen measles vaccine is not available.
Note (2): Vaccination recommendations

Children: CDC recommends routine childhood immunization for MMR vaccine starting with the first dose at 12 through 15 months of age, and the second dose at 4 through 6 years of age or at least 28 days following the first dose.
Students at post-high school educational institutions: Students at post-high school educational institutions without evidence of measles immunity need two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose.
Adults: People who are born during or after 1957 who do not have evidence of immunity against measles should get at least one dose of MMR vaccine.
International travelers: People 6 months of age or older who will be traveling internationally should be protected against measles. Before travelling internationally,

Infants 6 through 11 months of age should receive one dose of MMR vaccine
Children 12 months of age or older should have documentation of two doses of MMR vaccine (the first dose of MMR vaccine should be administered at age 12 months or older; the second dose no earlier than 28 days after the first dose)
Teenagers and adults born during or after 1957 without evidence of immunity against measles should have documentation of two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose

1.1.2. Post-exposure Prophylaxis

1.1.2.1. Indication

People exposed to measles who cannot readily show that they have evidence of immunity against measles should be offered post-exposure prophylaxis (PEP) or be excluded from the setting (school, hospital, childcare). MMR vaccine, if administered within 72 hours of initial measles exposure, or immunoglobulin (IG), if administered within six days of exposure, may provide some protection or modify the clinical course of disease.

Note (1): If MMR vaccine is not administered within 72 hours of exposure as PEP, MMR vaccine should still be offered at any interval following exposure to the disease in order to offer protection from future exposures. People who receive MMR vaccine or IG as PEP should be monitored for signs and symptoms consistent with measles for at least one incubation period.
Note (2): If many measles cases are occurring among infants younger than 12 months of age, measles vaccination of infants as young as 6 months of age may be used as an outbreak control measure. Note that children vaccinated before their first birthday should be revaccinated when they are 12 through 15 months old and again when they are 4 through 6 years of age.
Note (3): People who are at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and people with severely compromised immune systems, should receive IG. Intramuscular IG (IGIM) should be given to all infants younger than 12 months of age who have been exposed to measles.
Note (4): For infants aged 6 through 11 months, MMR vaccine can be given in place of IG, if administered within 72 hours of exposure. Because pregnant women might be at higher risk for severe measles and complications, intravenous IG (IGIV) should be administered to pregnant women without evidence of measles immunity who have been exposed to measles. People with severely compromised immune systems who are exposed to measles should receive IGIV regardless of immunologic or vaccination status because they might not be protected by MMR vaccine.
Preferred regimen: The recommended dose of IGIM is 0.5 mL/kg of body weight (maximum dose = 15 mL) and the recommended dose of IGIV is 400 mg/kg.
Note (5): If a healthcare provider without evidence of immunity is exposed to measles, MMR vaccine should be given within 72 hours, or IG should be given within 6 days when available. Exclude healthcare personnel without evidence of immunity from duty from day 5 after first exposure to day 21 after last exposure, regardless of post-exposure vaccine.

1.2. Treatment

Note (1): There is no specific antiviral therapy for measles. Medical care is supportive and to help relieve symptoms and address complications such as bacterial infections.
Note (2): Severe measles cases among children, such as those who are hospitalized, should be treated with vitamin A. Vitamin A should be administered immediately on diagnosis and repeated the next day. The recommended age-specific daily doses are

50,000 IU for infants younger than 6 months of age
100,000 IU for infants 6–11 months of age
200,000 IU for children 12 months of age and older

Middle East respiratory syndrome Return to Top

Middle East Respiratory Syndrome treatment

Preferred regimen: supportive care. There is no antiviral recommended for this infection at this moment, even though experimental therapies are at research (IFNs, Ribavirin, Lopinavir, Mycophenolic acid, Cyclosporine, Chloroquine, Chlorpromazine, Loperamide, 6-mercaptopurine and 6-thioguanine). Supportive care include: administer oxygen to patients with severe acute pulmonary infection with signs of respiratory distress, hypoxaemia or shock; use conservative fluids management, avoid administering high-dose systemic glucocorticoids, use non-invasive ventilation, but, if its nor effective, do not delay endotracheal intubation; use lung-protective strategy for intubated patients, recognize sepsis as early as possible and treat it accordingly.^[396]

Parainfluenza virus

Parainfluenza virus Return to Top

Parainfluenza virus^[397]

1. Adults

Preferred regimen: Ribavirin PO/IV 10 mg/kg q8h

Day 1: Start with 600 mg loading dose,then 200 mg q8h
Day 2: 400 mg q8h
Day 3: Increase the dose to a maximum of 10 mg/kg q8h

1.1 In case of adverse events

Preferred regimen: Decrease dose or discontinue Ribavirin

1.2 Creatinine clearance

30–50 mL/min: Ribavirin PO/IV maximal 200 mg q8h
10–30 mL/ min: No recommendation can be given

Parvovirus B19 Return to Top

Parvovirus B19^[398]

1. Erythema infectiosum

Supportive therapy: Symptomatic treatment only

2. Arthritis/arthalgia

Preferred regimen: Nonsteroidal anti-inflammatory drugs (NSAID)

3.Transient aplastic crisis

Supportive therapy: Transfusions and oxygen

4. Fetal hydrops

Supportive therapy: Intrauterine blood transfusion

5. Chronic infection with anemia

Preferred regimen: IVIG and transfusion

6.Chronic infection without anemia

Preferred regimen: IVIG

Note (1): Diagnostic tools are IgM and Igb antibody titers.Perhaps better is blood Parvovirus PCR.

Note (2): Dose of IVIG not standardized; suggest 400 mg/kg IV of commercial IVIG for 5 or 10 days or 1000 mg/kg IV for 3 days.

Note (3): Most dramatic anemias in pts with pre-existing hemolytic anemia.

Note (4): Bone marrow shown erythrocyte maturation arrest with giant pronormoblasts.

BK virus Return to Top

Human polyomavirus (BK virus) treatment

Maintenance regimen consisting of triple immunosuppression therapy: Calcineurin inhibitor (Cyclosporine or Tacrolimus) AND an antimetabolite (Azathioprine, Mycophenolate mofetil, or Mycophenolate sodium), AND Prednisone is to discontinue completely the antimetabolite (usually Mycophenolate) and decrease the dose of the Calcineurin inhibitor.
Alternative regimen (1): Decrease the Mycophenolate dose by 50 percent, followed by a 50 percent decrease in the Calcineurin inhibitor at three months if decoy cells persist. If using this approach, the target serum Tacrolimus trough level is 4 to 6, and the target serum Cyclosporine trough level is 60 to 100 ng/mL. Mycophenolate may be discontinued completely if viral activation persists. Maintenance immunosuppression then consists of Tacrolimus and low-dose Prednisone.
Alternative regimen (2): Reduce both the Calcineurin inhibitor and the Mycophenolate, which allows both the targeting of two pathways and lower total immunosuppression.

Note (1): For those who are hypogammaglobulinemic, we administer intravenous immunoglobulins (IV IG) in replacement doses of 500 mg/kg. Quantitative immunoglobulins should be checked two to three months later to determine whether hypogammaglobulinemia has recurred. Intravenous immunoglobulins (IV IG) is also an option in certain settings, based upon polymerase chain reaction (PCR) and kidney biopsy results. IVIG may contain antibodies against BK and JC virus since these viruses are ubiquitous in the general population.
Note (2): The goals of decreased immunosuppressive therapy are to restrain viral replication without triggering rejection.
Note (3): Reduced immunosuppression (defined as lowering mean doses of Mycophenolate and Tacrolimus) resulted in the successful elimination of viremia (mean period of six months) and allograft survival.
Note (4): Alternative approaches to reducing immunosuppression have also been effective

4.1 Changing from Tacrolimus to low-dose Cyclosporine not only reduces the effect of the Calcineurin inhibitor, but also reduces Mycophenolate concentrations.
4.2 Replacing the Calcineurin inhibitor with Sirolimus, with or without discontinuation of the antimetabolite, has the advantage of avoiding the long-term Calcineurin inhibitor-related nephrotoxic effects.
4.3 Lowering the dose of Calcineurin inhibitors may slow the loss of renal function.

Primary Regimens

Decrease immunosuppression if possible. (Cornerstone of Treatment)
Suggested antiviral therapy is based on anecdotal data. If progressive renal dysfunction:
Fluoroquinolone AND IVIG 500 mg/kg IV AND Leflunomide 100 mg for daily for 3 days, then 10-20 mg PO daily
If refractory to all of the above, add Cidofovir 5 mg/kg once per week for 2 weeks, then once every other week if refractory to all of the above

Ancillary Therapies in BK Virus Nephropathy

Cidofovir 0.25-1.0 mg/kg IV biweekly for 8 wk without Probenecid, prehydration recommended
Leflunomide 100 mg loading dose for 3 days, 20-60 mg/day, goal Leflunomide trough 50-100 ng/mL (consider lower trough goals of 20-40 ng/mL given hemolysis risk)
IV Ig 1-2 g/kg IV for 1-2 doses or 150 mg/kg IV biweekly for 8 wk
Fluoroquinolones-Ciproflaxacin 500 mg/day, duration dependent on virological response.

JC virus Return to Top

Progressive Multifocal Leukoencephalopathy (PML) caused by JC Virus ( John Cunningham virus) infections^[399]

There is no specific antiviral therapy for JC virus infection.

The main treatment approach is to reverse the immunosuppression caused by HIV.

Initiate anti retroviral therapy (ART) immediately in ART-naive patients .

Optimize ART in patients who develop Progressive Multifocal Leukoencephalopathy in phase of HIV viremia on ART .

Corticosteroids may be used for Progressive Multifocal Leukoencephalopathy- immune reconstitution inflammatory syndrome (IRIS) characterized by contrast enhancement, edema or mass effect, and with clinical deterioration

Rabies Return to Top

Preferred regimen: no specific therapeutics agents are available once the disease is established.

Note: There are vaccines and immune globulins available for postexposure prophylaxis:

Postexposure Prophylaxis for non immunized individuals: Wound cleansing, human rabies immune globulin - administer full dose infiltrated around any wound. Administer any remaining volume IM at other site anatomically distant from the wound. Administer vaccine 1,0ml, IM at deltoid area one each on days 0, 3, 7 and 14.
Postexposure Prophylaxis for immunized individuals: Wound cleansing, do not administer human rabies immune globulin. Administer vaccine 1,0ml, IM at deltoid area one each on days 0 and 3.

Respiratory Syncytial Virus Return to Top
Respiratory syncytial virus treatment

Supportive therapy

Hydration and supplemental oxygen.
Routine use of Ribavirin not recommended. Ribavirin therapy associated with small increases in O2 saturation.
No consistent decrease in need for mechanical ventilation or ICU stays. High cost, aerosol administration and potential toxicity^[400]

Note (1) In adults, Respiratory syncytial virus accounted for 10.6% of hospitalizations for pneumonia, 11.4% for COPD, 7.2% for asthma & 5.4% for CHF in pts >65 yrs of age ^[401]. Respiratory syncytial virus caused 11% of clinically important respiratory illnesses in military recruits^[402]

Note (2) Respiratory Syncytial Virus major cause of morbidity in neonates/infants.

Note (3) Nucleic acid test now approved to detect 12 respiratory viruses (xTAG Respiratory Viral Panel, Luminex Molecular Diagnostics).

Prevention of Respiratory syncytial virus

1. In children <24 months old with chronic lung disease of prematurity (formerly broncho-pulmonary dysplasia) requiring supplemental oxygen or
2. In premature infants (<32 wks gestation) and <6 months old at start of Respiratory syncytial virus season or
3. In children with selected congenital heart diseases.

Preferred regimen for prevention of Respiratory syncytial virus: Palivizumab (Synagis) 15 mg per kg IM q month Nov.-April^[400]

Note : Significant reduction in Respiratory syncytial virus hospitalization among children with congenital heart disease^[403]

Rhinovirus Return to Top
Rhinovirus treatment (commom cold)

Supportive therapy

Symptomatic treatment-Ipratropium bromide intranasal (2 sprays tid) AND Clemastine 1.34 mg 1–2 tab PO bid–tid (over the counter)
Symptomatic relief by Ipratropium nasal spray decreases rhinorrhea and sneezing vs placebo.^[404] AND Clemastine (an antihistamine) decreases sneezing, rhinorrhea but associated with dry nose, mouth & throat in 6–19%.^[405]OR Oral pleconaril given within 24 hrs of onset reduced duration (1 day) & severity of “cold symptoms” in DBPCT (p < .001).^[406]

Note (1)No antiviral rx indicated . ^[407]

Note (2) Found in 1/2 of children with community-acquired pneumonia; role in pathogenesis unclear (CID 39:681, 2004). ^[408]
Note (3) High rate of rhinovirus identified in children with significant lower resp tract infections ^[409]

Rotavirus Return to Top
Rotavirus treatment^[410], ^[411]

Treatment of diarrhoea caused by rotavirus

Rehydration with oral rehydration salts (ORS) solution. oral rehydration salts (ORS) solution is a mixture of clean water, salt and sugar. It costs a few cents per treatment. oral rehydration salts (ORS) solution is absorbed in the small intestine and replaces the water and electrolytes lost in the faeces.

Zinc supplements-with zinc supplements reduce the duration of a diarrhoea episode by 25% and are associated with a 30% reduction in stool volume.
Rehydration with intravenous fluids in case of severe dehydration or shock.
Nutrient-rich foods the vicious circle of malnutrition and diarrhoea can be broken by continuing to give nutrient-rich foods including breast milk during an episode, and by giving a nutritious diet including exclusive breastfeeding for the first six months of life to children when they are well.
Consulting a health professional , in particular for management of persistent diarrhoea or when there is blood in stool or if there are signs of dehydration.

Note (1): Rotavirus and Escherichia coli are the two most common etiological agents of diarrhoea in developing countries.

Note (2): There is no antiviral drug to treat rotavirus infection. Antibiotic drugs will not help because antibiotics fight against bacteria not viruses.

Note (3): Rotavirus infection can cause severe vomiting and diarrhea. This can lead to dehydration (loss of body fluids). During rotavirus infection, infants and young children, older adults, and people with other illnesses are most at risk becoming dehydrated.

Note (4): Symptoms of dehydration include decrease in urination, dry mouth and throat, feeling dizzy when standing up. A dehydrated child may also cry with few or no tears and be unusually sleepy or fussy.

Prevention

Access to safe drinking-water
Use of improved sanitation
Hand washing with soap

Exclusive breastfeeding for the first six months of life

Good personal and food hygiene
Health education about how infections spread; and Rotavirus vaccination.

Smallpox

Smallpox Return to Top

Smallpox ^[412]

Supportive care is the mainstay of therapy.
Currently, there are no anti-viral drugs of proven efficacy.
Recently, animal studies suggest that cidofovir and its cyclic analogues, given at the time of or immediately after exposure, have promise for the prevention of cowpox, vaccinia, and monkeypox.
Patients need adequate hydration and nutrition, because substantial amounts of fluid and protein can be lost by febrile persons with dense, often weeping lesions.

1. Secondary bacterial infection

Penicillinase-resistant antimicrobial agents should be used

If smallpox lesions are secondarily infected,

If bacterial infection endangers the eyes

Daily eye rinsing is required in severe cases.

Topical idoxuridine should be considered for the treatment of corneal lesions, although its efficacy is unproved for smallpox.

If the eruption is very dense and widespread.

HIV/AIDS

HIV/AIDS Return to Top

]* 1. Antiretroviral regimen options for treatment-naive patients^[413]

1.1. Integrase strand transfer inhibitor-based regimens

Preferred regimen (1): Dolutegravir 50 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative
Preferred regimen (2): Dolutegravir 50 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Preferred regimen (3): Elvitegravir 150 mg-Cobicistat 150 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd in patients with estimated CrCl ≥ 70 mL/min/1.73
Preferred regimen (4): Raltegravir 400 mg PO bid AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Alternative regimen (1): Efavirenz 600 mg PO qd OR Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Alternative regimen (2): Rilpivirine 25 mg PO qd AND (Tenofovir 300 mg PO qd OR Emtricitabine 200 mg PO qd) for patients with CD4 count >200 cells/microL
Alternative regimen (3): Raltegravir 400 mg PO bid AND (Abacavir 600 mg PO qd OR Lamivudine 300 mg PO qd) in patients who are HLA-B*5701-negative

1.2. Protease inhibitor-based regimen

Preferred regimen: Darunavir 800 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Alternative regimen (1): Atazanavir 300 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
Alternative regimen (2): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Alternative regimen (3): (Darunavir 800 mg-Cobicistat 150 mg PO qd OR Darunavir 800 mg-Ritonavir 100 mg PO qd) AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
Alternative regimen (4): Darunavir 800 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
Alternative regimen (5): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative and with pre-treatment HIV RNA <100,000 copies/mL
Alternative regimen (6): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
Alternative regimen (7): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd

1.3. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen

Alternative regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
Alternative regimen (2): Rilpivirine 25 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd

1.4. Other regimen options

1.4.1. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen

Preferred regimen (1): Efavirenz 600 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.

1.4.2. Other regimens when tenofovir or abacavir cannot be used

Preferred regimen (1): Darunavir 800 mg-Ritonavir 100 mg PO qd AND Raltegravir 400 mg PO qd only for patients with pre-treatment HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3.
Preferred regimen (2): Lopinavir 400 mg-Ritonavir 100 mg PO bid AND Lamivudine 300 mg PO bid

1.5. Pediatric doses

Abacavir 300 mg PO bid
Lamivudine 4 mg/kg/dose PO bid; maximum 150 mg PO bid
Stavudine 1 mg/kg/dose PO bid
Tenofovir 8 mg/kg/dose PO bid
Zidovudine 180-240 mg/m²/dose PO bid or 160 mg/m²/dose PO tid (range 90 mg/m²/dose-180 mg/m²/dose)
Lopinavir 400 mg PO bid
Nelfinavir 50 mg/kg/dose PO bid
Raltegravir 300 mg PO bid
Didanosine

20 to < 25 kg: 200 mg PO qd
25 to < 60 kg: 250 mg PO qd
≥60 kg: 400 mg PO qd

Efavirenz

10 to < 15 kg: 200 mg PO qd
15 to <20 kg: 250 mg PO qd
20 to < 25 kg: 300 mg PO qd
25 to < 32.5 kg: 350 mg PO qd
32.5 to <40 kg: 400 mg PO qd
≥ 40 kg: 600 mg PO qd

Nevirapine maximum 200 mg per dose

Between 1 day and 8 years: 200 mg/m²/dose PO qd for 14 days, then 200 mg/m²/dose PO bid
8 years and above: 120-150 mg/m²/dose PO qd for 14 days, then 120-150 mg/m²/dose PO bid

Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
Note (2): Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
Note (3): Rilpivirine should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
Note (4): Efavirenz should not be used in pregnant women.

2. Pre-exposure prophylaxis (PrEP)

Preferred regimen: Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd for ≤90-days
Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
Note (3): At 3 months and every 6 months thereafter, assess renal function.
Note (4): Every 6 months, test for bacterial STIs.

3. Post- exposure prophylaxis

Preferred regimen: Raltegravir 400 mg PO bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
Preferred basic regimen for low-risk exposures (Eg: mucus membrane):
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
Preferred expanded regimen for high-risk exposure (Eg: percutaneous needle stick)
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Note: Ideally therapy should be started within hours of exposure and continued for 28 days.

4. Perinatal antiretroviral regimen

4.1. Antepartum

4.1.1. Protease inhibitor-based regimen

Preferred regimen: (Tenofovir 300 mg-Emtricitabine 200 mg PO qd (fixed dose combination) OR Tenofovir 300 mg-Lamivudine 300 mg PO qd OR Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND (Atazanavir 300 mg-Ritonavir 100 mg PO qd OR Lopinavir 400 mg-Ritonavir 100 mg PO qd)

4.1.2. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:

Preferred regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg (fixed dose combination) PO qd
Preferred regimen (2): Efavirenz 600 mg-Tenofovir 300 mg-Lamivudine 300 mg PO qd
Alternative regimen: (Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND Efavirenz 600 mg PO qd

4.2. Intrapartum

Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous Zidovudine 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.

4.3. Postpartum

Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.

5. Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV

5.1 Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis

Preferred regimen: Zidovudine (ZDV) 100 mg PO given at birth and continued till six weeks
Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.

5.2. Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis

Nevirapine

Dose based on birth weight, initiated as soon after birth as possible.
Birth weight 1.5 to 2 kg: 8 mg/dose orally.
Birth weight >2 kg: 12 mg/dose orally.

AND

Zidovudine (ZDV)

Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.

≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
<30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.

Note (1): Three doses in the first week of life.
Note (2): First dose within 48 hours of birth (birth to 48 hrs).
Note (3): Second dose 48 hours after first.
Note (4): Third dose 96 hours after second.

6. Treatment and prevention of opportunistic infections

6.1. Pneumocystis pneumonia (PCP)

6.1.1. Prevention

Indication

CD4 count <200 cells/mm3
Oropharyngeal candidiasis
CD4 <14%
History of AIDS-defining illness
CD4 count >200 but <250 cells/mm3 if monitoring CD4 cell count every 3 months is not possible.

Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or 80 mg/400 mg PO qd
Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
Alternative regimen (2): Dapsone 100 mg PO qd or 50 mg PO bid
Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg-Leucovorin 25 mg) PO weekly
Alternative regimen (4): Dapsone 200 mg PO qd AND (Pyrimethamine 75 mg-Leucovorin 25 mg) PO weekly
Alternative regimen (5): Aerosolized Pentamidine 300 mg via Respigard nebulizer every month
Alternative regimen (6): Atovaquone 1500 mg PO qd
Alternative regimen (7): Atovaquone 1500 mg AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd

6.1.2. Treatment

6.1.2.1. For Moderate-to-Severe PCP'

Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day IV given q6h or q8h, may switch to PO after clinical improvement
Alternative regimen (1): Pentamidine 4 mg/kg IV daily infused over ≥60 minutes
Note: Reduce dose to 3 mg/kg IV daily if toxic.
Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 600 mg q6h IV OR 900 mg IV q8h OR Clindamycin 450 mg PO qid or 600 mg PO tid)

6.1.2.2. For Mild-to-Moderate PCP

Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day PO in TID OR Trimethoprim/sulfamethoxazole 160 mg/800 mg 2 tablets PO tid
Alternative regimen (1): Dapsone 100 mg PO qd AND TMP 5 mg/kg PO tid
Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 450 mg PO qid or 600 mg PO tid OR Atovaquone 750 mg PO bid with food)

6.1.3. Secondary prophylaxis, after completion of PCP treatment

Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO qd OR Trimethoprim/Sulfamethoxazole 80 mg/400 mg PO qd
Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
Alternative regimen (2): Dapsone 100 mg PO qd
Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (5): Dapsone 100 mg PO qd
Alternative regimen (6): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (7): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
Alternative regimen (8): Aerosolized Pentamidine 300 mg monthly via Respirgard nebulizer
Alternative regimen (9): Atovaquone 1500 mg PO qd
Alternative regimen (10): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd

6.1.4. Adjunctive corticosteroids

Indications- PaO2 <70 mmHg at room air OR Alveolar-arterial O2 gradient >35 mmHg.
Preferred regimen:

Days 1–5: 40 mg PO bid
Days 6–10: 40 mg PO qd
Days 11–21: 20 mg PO qd

Note (1): Trimethoprim/sulfamethoxazole should be permanently discontinued in patients with possible or definite stevens johnson syndrome or toxic epidermal necrosis.
Note (2): Whenever possible, patients should be tested for G6PD before use of Dapsone or Primaquine. Alternative regimen should be used in patients found to have G6PD deficiency.

6.2. Toxoplasma gondii encephalitis

6.2.1. Prevention

6.2.1.1. Indication

Toxoplasma IgG-positive patients with CD4 count <100 cells/µL.
Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cellsµL.
Prophylaxis should be initiated if seroconversion occurred.

Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd
Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
Alternative regimen (2): Trimethoprim/sulfamethoxazole 80 mg/400 mg PO qd
Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO weekly AND Leucovorin 25 mg PO weekly
Alternative regimen (4): Dapsone 200 mg PO weekly AND Pyrimethamine 75 mg PO weekly AND Leucovorin 25 mg PO weekly
Alternative regimen (5): Atovaquone 1500 mg PO qd
Alternative regimen (6): Atovaquone 1500 mg PO qd AND Pyrimethamine 25 mg PO qd AND Leucovorin 10 mg PO qd

6.2.2. Treatment

6.2.2.1. Treatment of acute infection

Preferred regimen: Pyrimethamine 200 mg PO single dose, followed by weight-based therapy:

If <60 kg, Pyrimethamine 50 mg PO qd AND Sulfadiazine 1000 mg PO qid AND Leucovorin 10–25 mg PO qd
If ≥60 kg, Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO qid AND Leucovorin 10–25 mg PO qd
Note: At least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.

Alternative regimen (1): Pyrimethamine 50 mg PO qdAND Leucovorin 10–25 mg PO qd AND Clindamycin 600 mg IV or PO q6h
Alternative regimen (2): Trimethoprim 5 mg/kg-Sulfamethoxazole 25 mg/kg IV or PO bid
Alternative regimen (3): Atovaquone 1500 mg PO bid with food AND Pyrimethamine 50 mg PO qd AND Leucovorin 10–25 mg PO qd
Alternative regimen (4): Atovaquone 1500 mg PO bid with food AND Sulfadiazine 1000–1500 mg PO qid (weight-based dosing, as in preferred therapy)
Alternative regimen (5): Atovaquone 1500 mg PO bid with food
Alternative regimen (6): Pyrimethamine 50 mg-Leucovorin 10–25 mg PO qd AND Azithromycin 900–1200 mg PO qd

6.2.2.2. Chronic maintenance therapy

Preferred regimen: Pyrimethamine 25–50 mg PO qd AND Sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
Alternative regimen (1): Clindamycin 600 mg PO tid AND Pyrimethamine 25–50 mg-Leucovorin 10–25 mg PO qd
Alternative regimen (2): Trimethoprim/sulfamethoxazole 160 mg/800 mg bid
Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND Pyrimethamine 25 mg-Leucovorin 10 mg PO qd
Alternative regimen (4): Atovaquone 750–1500 mg PO bid AND Sulfadiazine 2000–4000 mg PO qd in 2–4 divided doses
Alternative regimen (5): Atovaquone 750–1500 mg PO bid with food

6.3. Mycobacterium tuberculosis infection

6.3.1. Prevention

6.3.1.1. Indication

Positive screening test for latent tuberculosis infection, with no evidence of active tuberculosis, and no prior treatment for active tuberculosis or latent tuberculosis infection.
Close contact with a person with infectious tuberculosis, with no evidence of active tuberculosis, regardless of screening test results.
Preferred regimen: (Isoniazid 300 mg PO qd AND Pyridoxine 25 mg PO qd for 9 months) OR (Isoniazid 900 mg PO two times a week (by DOT) AND Pyridoxine 25 mg PO qd for 9 months)
Alternative regimen (1): Rifampin 600 mg PO qd for 4 months
Alternative regimen (2): Rifabutin (dose adjusted based on concomitant ART) PO qd for 4 months

6.3.2. Treatment

Preferred regimen

Initiation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) AND Pyrazinamide (upto 2000 mg) PO qd AND Ethambutol (upto 1600 mg) PO qd for initial phase for 2 months.

Continuation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) (5–7 times/week) or three times a week.
Duration of therapy:

Pulmonary tuberculosis: 6 months
Pulmonary tuberculosis and culture positive after 2 months of tuberculosis treatment: 9 months
Extra-pulmonary tuberculosis w/CNS infection: 9–12 months
Extra-pulmonary tuberculosis with bone or joint involvement: 6 to 9 months
Extra-pulmonary tuberculosis in other sites: 6 months
Total duration of therapy should be based on number of doses received, not on calendar time

6.3.1.3. Treatment for drug-resistant tuberculosis

Resistant to Isoniazid:

Preferred regimen (1): (Rifampin 600 mg PO qd OR Rifabutin 300mg PO qd) AND Ethambutol (upto 1600 mg) PO qd AND Pyrazinamide (upto 2000 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qd OR Levofloxacin 500-1000 mg PO or IV qd) for 2 months; followed by Rifampin 600 mg PO qd for 7 months.
Preferred regimen (2): Rifabutin 300mg PO qd AND Ethambutol (upto 1600 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qdOR Levofloxacin 500-1000 mg PO or IV qd) for 7 months

6.4. Disseminated mycobacterium avium complex (MAC) disease

6.4.1. Prevention

6.4.1.1. Indication-CD4 count <50 cells/µL—after ruling out active disseminated MAC disease based on clinical assessment

Preferred regimen (1): Azithromycin 1200 mg PO once weekly
Preferred regimen (2): Clarithromycin 500 mg PO bid
Preferred regimen (3): Azithromycin 600 mg PO twice weekly.

6.4.2. Treatment

Preferred regimen: Clarithromycin 500 mg PO bid AND Ethambutol 15 mg/kg PO qd OR Azithromycin 500–600 mg PO qd for at least 12 months of therapy
Note (1): Treatment can be discontinued if no signs and symptoms of MAC disease and sustained (>6 months) CD4 count >100 cells/µL in response to anti retroviral therapy.
Note (2): Addition of a third or fourth drug should be considered for patients with advanced immunosuppression (CD4 counts <50 cells/µL), high mycobacterial loads (>2 log CFU/mL of blood), or in the absence of effective anti retroviral therapy which include Amikacin 10–15 mg/kg IV qd, Streptomycin 1 g IV or IM qd, Moxifloxacin 400 mg PO qd, Levofloxacin 500 mg PO qd.

6.5. Streptococcus pneumoniae infection

6.5.1. Prevention

6.5.1.1. Indication

6.5.1.1.1. For individuals who have not received any pneumococcal vaccine, regardless of CD4 count

Preferred regimen: PCV13 0.5ml IM single dose
Alternative regimen: PPV23 0.5 mL IM or SQ single dose
Note (1): If CD4 count ≥200 cells/µL, administer PPV23 0.5 mL IM or SQ at least 8 weeks after the PCV13 vaccine.
Note (2): If CD4 count <200 cells/µL, PPV23 can be offered at least 8 weeks after receiving PCV13 or can wait until CD4 count increased to ≥200 cells/µL.

6.5.1.1.2. For individuals who have previously received PPV23

Note: One dose of PCV13 should be given atleast 1 year after the last receipt of PPV23

6.5.1.1.3. Re-vaccination

If age 19–64 years and ≥5 years since the first PPV23 dose PPV23 0.5 mL IM or SQ
If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ
If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ

6.6. Influenza A and B virus infection

6.6.1. Prevention

6.6.1.1. Indication

All HIV-infected patients
Note (1): Inactivated influenza vaccine annually (per recommendation for the season).
Note (2): Live-attenuated influenza vaccine is contraindicated in HIV-infected patients.

6.7. Syphilis

6.7.1. Prevention

6.7.1.1. Indication

For individuals exposed to a sex partner with a diagnosis of primary, secondary, or early latent syphilis within past 90 days.
For individuals exposed to a sex partner >90 days before syphilis diagnosis in the partner, if serologic test results are not available immediately and the opportunity for follow-up is uncertain.
Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 8– 10 days
Alternative regimen (3): Azithromycin 2 g PO single dose
Note: Azithromycin is not recommended for MSM or pregnant women.

6.7.2. Treatment

6.7.2.1. Early stage (primary, secondary, and early-latent syphilis)

Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 10–14 days
Alternative regimen (3): Azithromycin 2 g PO single dose

6.7.2.2. Late-stage (tertiary–cardiovascular or gummatous disease)

Preferred regimen: Benzathine penicillin G 2.4 million units IM weekly for 3 doses
Alternative regimen: Doxycycline 100 mg PO bid for 28 days

6.7.2.3. Neurosyphilis (including otic or ocular disease)

Preferred regimen: Aqueous crystalline Penicillin G 18– 24 million units per day (administered as 3–4 million units IV q4h or by continuous IV infusion) for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion of IV therapy
Alternative regimen: Procaine penicillin 2.4 million units IM q24h AND Probenecid 500 mg PO qid for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion
Note (1): The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgia that can occur within the first 24 hours after therapy for syphilis.
Note (2): This reaction occurs most frequently in patients with early syphilis, high nontreponemal titers and prior penicillin treatment.

6.8. Histoplasma capsulatum infection

6.8.1. Prevention

6.8.1.1. Indication

CD4 count ≤150 cells/µL and at high risk because of occupational exposure or live in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years).
Preferred regimen: Itraconazole 200 mg PO qd

6.8.2. Treatment

6.8.2.1. Moderately severe to severe disseminated disease

Induction therapy (for at least 2 weeks or until clinically improved)

Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h

Maintenance therapy:

Preferred regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid

6.8.2.2. Less severe disseminated disease

Induction therapy:

Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h
Alternative regimen: Amphotericin B lipid complex 3 mg/kg IV q24h OR Amphotericin B cholesteryl sulfate complete 3 mg/kg IV q24h
Note: Induction therapy should be for at least 2 weeks or until clinically improved.

Maintenance therapy:

Preferred regimen: Itraconazole 200 mg PO tid for 3 days and then Itraconazole 200 mg PO bid for 12 months
Alternative regimen (1): Voriconazole 400 mg PO bid for 1 day, then 200 mg bid
Alternative regimen (2): Posaconazole 400 mg PO bid
Alternative regimen (3): Fluconazole 800 mg PO qd

6.8.2.3. Meningitis

Induction therapy:

Preferred regimen: Liposomal amphotericin B 5 mg/kg/day for 4–6 weeks

Maintenance therapy:

Preferred regimen: Itraconazole 200 mg PO bid to tid for ≥1 year

Note: Treatment continued until resolution of abnormal CSF findings.
Long-Term Suppression Therapy

Preferred regimen: Itraconazole 200 mg PO qd
Alternative regimen: Fluconazole 400 mg PO qd
Note: Therapeutic drug monitoring and dosage adjustment may be necessary to ensure Triazole antifungal and ARV efficacy and reduce concentration-related toxicities.

6.9. Coccidioidomycosis

6.9.1. Prevention
6.9.1.1. Indication

A new positive IgM or IgG serologic test in patients who live in a disease-endemic area and with CD4 count <250 cells/µL.
Preferred regimen: Fluconazole 400 mg PO qd

6.9.2. Treatment

6.9.2.1. Clinically mild infections (e.g., focal pneumonia)

Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid

6.9.2.2. Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)

Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV qd OR Lipid formulation Amphotericin B 4–6 mg/kg IV qd
Alternative regimen: Fluconazole or Itraconazole, with Itraconazole preferred for bone disease 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped.

6.9.2.3. Meningeal infections

Preferred regimen: Fluconazole 400–800 mg IV or PO qd
Alternative regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid

6.9.2.4. Chronic suppressive therapy

Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
Note (1): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/µL.
Note (2): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy.

6.10. Herpes simplex virus (HSV) Disease

6.10.1. Orolabial lesions (For 5–10 Days)

Preferred regimen (1): Valacyclovir 1 g PO bid
Preferred regimen (2): Famciclovir 500 mg PO bid
Preferred regimen (3): Acyclovir 400 mg PO tid

6.10.2. Initial or recurrent genital HSV (For 5–14 Days)

Preferred regimen (1): Valacyclovir 1 g PO bid
Preferred regimen (2): Famciclovir 500 mg PO bid
Preferred regimen (3): Acyclovir 400 mg PO tid

6.10.3. Severe mucocutaneous HSV

Preferred regimen: Initial therapy Acyclovir 5 mg/kg IV q8h.
Note: After lesions begin to regress, change to PO therapy as above. Continue until lesions are completely healed.

6.10.4. Chronic suppressive therapy

Preferred regimen (1): Valacyclovir 500 mg PO bid
Preferred regimen (2): Famciclovir 500 mg PO bid
Preferred regimen (3): Acyclovir 400 mg PO bid

6.10.4. For acyclovir-resistant HSV

Preferred therapy: Foscarnet 80–120 mg/kg/day IV q12h-q8h
Alternative regimen: Cidofovir IV OR Topical Trifluridine OR Topical Imiquimod for 21-28 days
Note: Continue indefinitely regardless of CD4 cell count.

6.11. Varicella-zoster virus (VZV) infection

6.11.1. Varicella-zoster virus (VZV) infection

6.11.1.2 Prevention

6.11.1.1. Pre-exposure prevention

Indication: Patients with CD4 counts ≥200 cells/µL who have not been vaccinated, have no history of varicella or herpes zoster, or who are seronegative for VZV.
Preferred regimen: Primary varicella vaccination, 2 doses (0.5 mL SQ each) administered 3 months apart
Alternative regimen: VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts
Note (1): Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
Note (2): If vaccination results in disease because of vaccine virus, treatment with Acyclovir is recommended.

6.11.1.2. Post-exposure prevention

Indication: Close contact with a person with chickenpox or herpes zoster; and is susceptible (i.e., no history of vaccination or of either condition, or known to be VZV seronegative).
Preferred regimen: Varicella-zoster immune globulin (VariZIG™) 125 international units per 10 kg (maximum 625 international units) IM, administered as soon as possible and within 10 days after exposure.
Alternative regimen (1): Acyclovir 800 mg PO qd for 5– 7 days
Alternative regimen (2): Valacyclovir 1 g PO tid for 5–7 days
Note (1): Individuals receiving monthly high-dose IVIG (>400 mg/kg) are likely to be protected if the last dose of IVIG was administered <3 weeks before exposure.
Note (2): If antiviral therapy is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.

6.11.1.2. Treatment

6.11.1.2.1 Primary varicella infection (chickenpox)

6.11.1.2.1. Uncomplicated cases (For 5–7 Days)

Preferred regimen (1): Valacyclovir 1 g PO tid
Preferred regimen (2): Famciclovir 500 mg PO tid

6.11.1.2.1. Severe or complicated Cases

Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days.
Alternative regimen: Acyclovir 800 mg PO 5 times/day for 5-7 days.

6.11.1.2.2. Herpes zoster (Shingles)

6.11.1.2.2.1. Acute localized dermatomal

Preferred regimen (1): Valacyclovir 1 g PO tid for 7–10 days; consider longer duration if lesions are slow to resolve
Preferred regimen (2): Famciclovir 500 mg tid for 7–10 days; consider longer duration if lesions are slow to resolve

6.11.1.2.2.2. Extensive cutaneous lesion or visceral involvement

Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident.
Note: Treatment may switch to PO therapy (Valacyclovir, Famciclovir, or Acyclovir) after clinical improvement (i.e., when no new vesicle formation or improvement of signs and symptoms of visceral VZV), to complete a 10–14 day course.
Alternative regimen: Acyclovir 800 mg PO 5 times/day for 7–10 days; consider longer duration if lesions are slow to resolve.

6.11.1.2.2.3. Progressive outer retinal necrosis (PORN)

Preferred regimen: (Ganciclovir 5 mg/kg with or without Foscarnet 90 mg/kg) IV q12h AND (Ganciclovir 2 mg/0.05mL with or without Foscarnet 1.2 mg/0.05 ml) intravitreal injection biweekly.

6.11.1.2.2.4. Acute retinal necrosis (ARN)

Preferred regimen: Acyclovir 10-15 mg/kg IV q8h AND (Ganciclovir 2 mg/0.05mL intravitreal injection 1-2 doses biweekly for 10-14 days, followed by Valacyclovir 1g PO tid for 6 weeks

6.12. Cytomegalovirus (CMV) Disease

6.12.1. Treatment

6.12.1.1. CMV retinitis

Induction therapy

Preferred regimen (1): Ganciclovir 2mg OR Foscarnet 2.4mg intravitreal injections for 1-4 doses over a period of 7-10 days to achieve high intraocular concentration faster
Preferred regimen (2): Valganciclovir 900 mg PO bid for 14–21 days
Alternative regimen (1): Ganciclovir 5 mg/kg IV q12h for 14–21 days
Alternative regimen (2): Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 14–21 days
Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks
Note: Saline hydration before and after therapy should be given and Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g) is recommended.

Chronic maintenance (secondary prophylaxis):

Preferred regimen: Valganciclovir 900 mg PO qd
Alternative regimen (1): Ganciclovir 5 mg/kg IV 5–7 times weekly
Alternative regimen (2): Foscarnet 90–120 mg/kg IV once daily
Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks; saline hydration before and after therapy AND Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g)

6.12.1.2. CMV esophagitis or colitis

6.12.1.2.1. Severe condition

Preferred regimen: Ganciclovir 5 mg/kg IV q12h; may switch to Valganciclovir 900 mg PO bid once the patient can tolerate oral therapy for 21-42 days or till the symptoms are resolved
Alternative regimen: Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 21-42 days
Note: For patients with treatment-limiting toxicities to Ganciclovir or with Ganciclovir resistance, above regimen is recommended.

6.12.1.2.2. Mild disease and able to tolerate oral therapy

Preferred regimen: Valganciclovir 900 mg PO bid 21-42 days

6.12.1.3. CMV neurological disease

Preferred regimen: Ganciclovir 5 mg/kg IV q12h AND (Foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q8h) to stabilize disease

6.13. HHV-8 Diseases (kaposi sarcoma [KS], primary effusion lymphoma [PEL], multicentric castleman’s disease [MCD])

6.13.1. Treatment

Mild to moderate KS (ACTG Stage T0)

Note: Initiate or optimize anti retroviral therapy.

Advanced KS [ACTG Stage T1, Including Disseminated Cutaneous (AI) Or Visceral KS]

Note: Chemotherapy (per oncology consult) AND anti retroviral therapy.

Primary effusion lymphoma

Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
Preferred regimen (3): Valganciclovir 900 mg PO bid AND Zidovudine 600 mg PO qid for 7– 21 days
Alternative regimen: Rituximab (375 mg/m² given weekly for 4–8 weeks) may be an alternative to or used adjunctively with antiviral therapy
Note: Valganciclovir PO OR Ganciclovir IV can be used as adjunctive therapy

6.14. Human papillomavirus (HPV) infection

6.14.1. Prevention

For females aged 13–26 years

Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6 OR HPV bivalent vaccine 0.5 mL IM at months 0, 1–2, and 6

Males aged 13–26 years

Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6

6.14.2. Treatment

6.14.2.1. Patient-applied therapy for uncomplicated external warts that can be easily identified by patients

Preferred regimen (1): Podophyllotoxin (e.g., podofilox 0.5% solution or 0.5% gel)
Note: Apply to all lesions bid for 3 consecutive days, followed by 4 days of no therapy, repeat weekly for up to 4 cycles, until lesions are no longer visible)
Preferred regimen (2): Imiquimod 5% cream
Note: Apply to lesion at bedtime and remove in the morning on 3 nonconsecutive nights weekly for up to 16 weeks, until lesions are no longer visible. Each treatment should be washed with soap and water 6–10 hours after application.
Preferred regimen (3): Sinecatechins 15% ointment
Note: Apply to affected areas tid for up to 16 weeks, until warts are completely cleared and not visible

6.14.2.2. Provider-applied therapy for complex or multicentric lesions, or lesions inaccessible to patient

Note (1): Cryotherapy (liquid nitrogen or cryoprobe): Apply until each lesion is thoroughly frozen. Repeat every 1–2 weeks for up to 4 weeks, until lesions are no longer visible. Some providers allow the lesion to thaw, then freeze a second time in each session.
Note (2): Trichloroacetic acid or bichloroacetic acid cauterization: 80%–90% aqueous solution, apply to wart only, allow to dry until a white frost develops. Repeat weekly for up to 6 weeks, until lesions are no longer visible.
Note (3): Surgical excision or laser surgery to external or anal warts.
Note (4): Podophyllin resin 10%–25% in tincture of benzoin: Apply to all lesions (up to 10 cm2 ), then wash off a few hours later, repeat weekly for up to 6 weeks until lesions are no longer visible.

6.15. Hepatitis A virus (HAV) infection

6.15.1. Prevention

Indication: HAV-susceptible patients with chronic liver disease, or who are injection-drug users or homosexuals
Preferred regimen: Hepatitis A vaccine 1 mL IM 2 doses at 0 and 6–12 months.
Alternative regimen: Combined HAV and HBV vaccine 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months).
Note (1): For patients susceptible to both HAV and hepatitis B virus (HBV) infection, alternative regimen is recommended.
Note (2): IgG antibody response should be assessed 1 month after vaccination; nonresponders should be revaccinated when CD4 count >200 cells/µL.

6.16. Hepatitis B virus (HBV) infection

6.16.1. Prevention

6.16.1.1. Indication

Patients without chronic HBV or without immunity to HBV (i.e., anti-HBs <10 international units/mL).
Patients with isolated anti-HBc and negative HBV DNA.
Early vaccination is recommended before CD4 count falls below 350 cells/µL.
However, in patients with low CD4 cell counts, vaccination should not be deferred until CD4 count reaches >350 cells/µL, because some patients with CD4 counts <200 cells/µL do respond to vaccination.
Preferred regimen (1): HBV vaccine IM (Engerix-B 20 µg/mL or Recombivax HB 10 µg/mL), 0, 1, and 6 months
Preferred regimen (2): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL) 0, 1, 2 and 6 months
Preferred regimen (3): Combined HAV and HBV vaccine, 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months)
Alternative regimen: Some experts recommend vaccinating with 40-µg doses of either HBV vaccine
Note: Anti-HBs should be obtained 1 month after completion of the vaccine series. Patients with anti-HBs <10 international units/mL at 1 month are considered nonresponders.
Vaccine Non-Responders:

Preferred regimen (1): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL), 0, 1, 2 and 6 months.
Note (1): Vaccination non-responders have anti-HBs <10 international units/mL 1 month after vaccination series.
Note (2): For patients with low CD4 counts at time of first vaccine series, some experts might delay revaccination until after a sustained increase in CD4 count with anti retroviral therapy.

6.16.2. Treatment

Preferred regimen: Tenofovir 300 mg PO qdAND Emtricitabine 200 mg PO qd OR Lamivudine 300 mg PO qd AND additional drug(s) for HIV
Note: Anti retroviral therapy regimen should include 2 drugs that are active against both HBV and HIV.
Alternative regimen: Peginterferon alfa-2a 180 μg SQ once weekly for 48 weeks OR Peginterferon alfa 2b 1.5 μg/kg SQ once weekly for 48 weeks.
Note: For HBV treatment is indicated for patients with elevated ALT and HBV DNA >2,000 IU/mL significant liver fibrosis, advanced liver disease or cirrhosis, above regimen is indicated.

6.17. Penicilliosis marneffei

6.17.1. Prevention

6.17.1.1. Indication

Patients with CD4 cell counts <100 cells/µL who live or stay for a long period in rural areas in northern Thailand, Vietnam, or Southern China.
Preferred regimen: Itraconazole 200 mg PO qd
Alternative regimen: Fluconazole 400 mg PO once weekly

6.17.2. Treatment

6.17.2.1. For acute infection in severely ill patients

Preferred regimen: Liposomal amphotericin B 3–5 mg/kg/day IV for 2 weeks, followed by Itraconazole 200 mg PO bid for 10 weeks, followed by chronic maintenance therapy
Alternative regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h for at least 3 days, followed by 200 mg PO bid for a maximum of 12 weeks, followed by maintenance therapy

6.17.2.2. For mild disease

Preferred regimen: Itraconazole 200 mg PO bid for 8 weeks; followed by chronic maintenance therapy
Alternative regimen: Voriconazole 400 mg PO bid for 1 day, then 200 mg bid for a maximum of 12 weeks, followed by chronic maintenance therapy

6.17.2.3. Chronic Maintenance Therapy (Secondary Prophylaxis)

Preferred regimen: Itraconazole 200 mg PO qd
Note (1): Anti retroviral therapy should be initiated simultaneously with treatment for penicilliosis to improve treatment outcome.
Note (2): Itraconazole and Voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bi-directional.
Note (3): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities.

6.18. Isosporiasis

6.18.1. Treatment

For Acute Infection:

Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) qid for 10 days
Preferred regimen (2): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) bid for 7–10 days
Alternative regimen (1): Pyrimethamine 50–75 mg PO daily AND Leucovorin 10–25 mg PO qd
Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days as a second line alternative

Chronic Maintenance Therapy (Secondary Prophylaxis):

Preferred regimen (1): In patients with CD4 count <200/µL, Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times a week
Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or (320 mg/1600 mg) three times a week
Alternative regimen (2): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
Alternative regimen (3): Ciprofloxacin 500 mg three times a week as a second-line alternative
Note (1): Fluid and electrolyte management in patients with dehydration.
Note (2): Immune reconstitution with anti retroviral therapy may result in fewer relapses.
Note (3): IV therapy may be used for patients with potential or documented mal-absorption.

6.19. Chagas disease (American trypanosomiasis)

6.19.1. Treatment

For acute, earlychronic, and reactivated Disease:

Preferred regimen: Benznidazole 5–8 mg/kg/day PO in 2 divided doses for 30–60 days
Alternative regimen: Nifurtimox 8–10 mg/kg/day PO for 90–120 days.

6.20. Leishmaniasis, visceral

6.20.1. Leishmaniasis, visceral

6.20.1.1. Treatment

For initial infection:

Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV qd
Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38)
Alternative regimen (1): Amphotericin B deoxycholate 0.5–1.0 mg/kg IV q24h for total dose of 1.5–2.0 g
Alternative regimen (2): Sodium stibogluconate (pentavalent antimony) 20 mg/kg IV or IM q24h for 28 days
Alternative regimen (3): Miltefosine 100 mg PO qd for 4 weeks

Chronic maintenance therapy (secondary prophylaxis); Especially in Patients with CD4 Count <200 cells/µL:

Preferred regimen (1): Liposomal amphotericin B 4 mg/kg every 2–4 weeks
Preferred regimen (2): Amphotericin B lipid complex 3 mg/kg every 21 days
Alternative regimen: Sodium stibogluconate 20 mg/kg IV or IM every 4 weeks

6.20.2. Leishmaniasis, cutaneous

Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV daily for 10 days
Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg
Preferred regimen (3): Sodium stibogluconate 20 mg/kg IV or IM daily for 3–4 weeks

6.21. Aspergillosis, invasive

6.21.1. Treatment

Preferred regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h, followed by Voriconazole 200 mg PO q12h after clinical improvement until CD4 cell count >200 cells/µL and the infection appears to be resolved.
Alternative regimen (1): Lipid formulation of Amphotericin B 5 mg/kg IV q24h
Alternative regimen (2): Amphotericin B deoxycholate 1mg/kg IV q24h
Alternative regimen (3): Caspofungin 70 mg IV single dose, then 50 mg IV q24h
Alternative regimen (4): Micafungin 100–150 mg IV q24h
Alternative regimen (5): Anidulafungin 200 mg IV single dose, then 100 mg IV q24h
Alternative regimen (6): Posaconazole 200 mg PO qid, then, after condition improved, 400 mg PO bid

6.22. Malaria

6.22.1. Prevetion

6.22.1.1. Prophylaxis in all areas

Preferred regimen (1): Atovaquone 250 mg and Proguanil hydrochloride 100 mg PO qd
Pediatric doses: Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride

5–8 kg: 1/2 pediatric tablet daily
>8–10 kg: 3/4 pediatric tablet daily
>10–20 kg: 1 pediatric tablet daily
>20–30 kg: 2 pediatric tablets daily
>30–40 kg: 3 pediatric tablets daily

Note (1): Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with severe renal impairment (creatinine clearance <30 mL/min).
Note (2): Atovaquone-proguanil should be taken with food or a milky drink. Not recommended for prophylaxis for children weighing <5 kg, pregnant women, and women breastfeeding infants weighing <5 kg. Partial tablet doses may need to be prepared by a pharmacist and dispensed in individual capsules.
Preferred regimen (2): Doxycycline 100 mg PO qd
Pediatric dose: ≥8 years of age: 2.2 mg/kg up to adult dose of 100 mg/day
Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in children <8 years of age and pregnant women.

6.22.1.2. Prophylaxis only in areas with chloroquine-sensitive malaria

Preferred regimen: Chloroquine phosphate 300 mg base (500 mg salt) PO once a week
Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. May exacerbate psoriasis.
Alternative regimen: Hydroxychloroquine sulfate 400 mg salt PO once a week
Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas.
Pediatric doses: Chloroquine phosphate 5 mg/kg base (8.3 mg/kg salt) orally, once/week, up to maximum adult dose of 300 mg base; Hydroxychloroquine sulfate 5 mg/kg base (6.5 mg/kg salt) orally, once/week, up to a maximum adult dose of 310 mg base

6.22.1.3. Prophylaxis in areas with mefloquine-sensitive malaria

Preferred regimen: Mefloquine 250 mg PO once a week
Note (1): Begin ≥2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in people allergic to mefloquine or related compounds (quinine, quinidine) and in people with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures.
Note (2): Use with caution in persons with psychiatric disturbances or a previous history of depression. Not recommended for persons with cardiac conduction abnormalities.
Pediatric dose: Mefloquine ≤9 kg: 4.6 mg/kg base (5 mg/kg salt) orally, once/week

>9–19 kg: 1/4 tablet once/week
>19–30 kg: 1/2 tablet once/week
>30–45 kg: 3/4 tablet once/week
>30–45 kg: 3/4 tablet once/week

6.22.1.4. Prophylaxis for short-duration travel to areas with principally Plasmodium vivax

Preferred regimen: Primaquine 52.6 mg PO qd
Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily

6.22.1.5. Terminal prophylaxis to decrease the risk for relapses of Plasmodium vivax and Plasmodium ovale

Preferred regimen: Primaquine 52.6 mg PO qd for 14 days after departure from the malarious area
Note: Indicated for people who have had prolonged exposure to P. vivax, P. ovale, or both. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily for 14 days after departure from the malarious area

6.22.2. Treatment

Note (1): Patients coinfected with HIV should avoid Artesunate AND Sulfadoxine-Pyrimethamine if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving Efavirenz OR Zidovudine.
Note (2): Because Plasmodium falciparum malaria can progress within hours from mild symptoms or low-grade fever to severe disease or death, all HIV-infected patients with confirmed or suspected P. falciparum infection should be hospitalized for evaluation, initiation of treatment, and observation.
6.22.2.1. Plasmodium falciparum^[414]

6.22.2.1.1. Treatment of uncomplicated Plasmodium falciparum malaria

6.22.2.1.1.1. Treat children and adults with uncomplicated Plasmodium falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)

Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days
Note: The first two doses should, ideally, be given 8 hours apart.
Dosage regimen based on Body weight (kg)

Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days

Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
Note: A total therapeutic dose range of 6–30 mg/kg/day Artesunate and 22.5–45 mg/kg/day per dose Amodiaquine is recommended.
Dosage regimen based on body weight (kg)

Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days

Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days
Dosage regimen based on body weight (kg)

Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days

Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
Dosage regimen based on body weight (kg)

Body weight (kg)- 5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
Body weight (kg)- 10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
Body weight (kg)- 25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1

Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days
Dosage regimen based on Body weight (kg)

Body weight (kg)-5 to < 8: Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
Body weight (kg)-8 to < 11: Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
Body weight (kg)-11 to < 17: Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
Body weight (kg)-17 to < 25: Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
Body weight (kg)-25 to < 36: Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
Body weight (kg)-36 to < 60: Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
Body weight (kg)-60 < 80: Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
Body weight (kg)- >80: Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days

6.22.2.1.1.2 Reducing the transmissibility of treated Plasmodium falciparum infections In low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

Preferred regimen: Primaquine 0.25 mg/kg PO single dose with ACT

6.22.2.1.2. Recurrent falciparum malaria

6.22.2.1.2.1. Failure within 28 days

Note: The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens with Artesunate or Quinine both of which should be co-administered with Tetracycline, or Doxycycline or Clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.

6.22.2.1.2.2. Failure after 28 days

Note: All presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of Mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.

6.22.2.1.3. Reducing the transmissibility of treated Plasmodium falciparum infections in low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)

Note: Single dose of 0.25 mg/kg biweekly Primaquine with ACT

6.22.2.1.4. Treating uncomplicated Plasmodium falciparum malaria in special risk groups

6.22.2.1.4.1. Pregnancy

First trimester of pregnancy : Quinine AND Clindamycin 10 mg/kg/day PO bid for 7 days
Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
Note (2): Primaquine and Tetracyclines should not be used in pregnancy.

6.22.2.1.4.2. Infants less than 5kg body weight

Note: They should be treated with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.

6.22.2.1.4.4. Large and obese adults

Note: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.

6.22.2.1.4.5. Non-immune travellers

Note: Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.

6.22.2.1.4.6. Uncomplicated hyperparasitaemia

Note: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.

6.22.2.2. Treatment of uncomplicated malaria caused by Plasmodium vivax, Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi

6.22.2.2.1. Blood Stage infection

6.22.2.2.1.1. Uncomplicated malaria caused by Plasmodium vivax

6.22.2.2.1.1.1. In areas with chloroquine-sensitive Plasmodium vivax

Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day PO

6.22.2.2.1.1.2. In areas with chloroquine-resistant Plasmodium vivax

Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate AND Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin AND Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether ANDLumefantrine) OR (Artesunate AND Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.

6.22.2.2.1.2. Uncomplicated malaria caused by Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi malaria

Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to Chloroquine. In only one study, conducted in Indonesia, was resistance to Chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.

6.22.2.2.1.3. Mixed malaria infections

Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.

6.22.2.2.2. Liver stages (hypnozoites) of Plasmodium vivax and Plasmodium ovale

Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of Primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.

6.22.2.2.2.1. Primaquine for preventive relapse

Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days

6.22.2.2.2.2. Primaquine and glucose-6-phosphate dehydrogenase deficiency

Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks
Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.

6.22.2.2.2.3. Prevention of relapse in pregnant or lacating women and infants

Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient)

6.22.2.3. Treatment of severe malaria

6.22.2.3.1. Treatment of severe falciparum infection with Artesunate

6.22.2.3.1.1. Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women)

Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).

6.22.2.3.1.2. Young children weighing < 20 kg

Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
Alternative regimen: use Artemether in preference to quinine for treating children and adults with severe malaria

6.22.2.3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)

6.22.2.3.2.1. Adults and children

Preferred regimen: Artesunate IM q24h
Alternative regimen: Artemether IM OR Quinine IM

6.22.2.3.2.2. Children < 6 years

Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
Note: Do not use rectal artesunate in older children and adults.

6.22.2.3.3. Pregancy

Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.

6.22.2.3.4. Treatment of severe Plasmodium Vivax infection

Note: Parenteral Artesunate, treatment can be completed with a full treatment course of oral ACT or Chloroquine (in countries where Chloroquine is the treatment of choice). A full course of radical treatment with Primaquine should be given after recovery.

6.22.2.3.5. Additional aspects of management in severe malaria

Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
Blood Transfusion: In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.

6.23. Cryptococcosis

6.23.1. Treatment

6.23.1.1. Cryptococcal meningitis

6.23.1.1.1. Induction therapy

Preferred regimen: Liposomal amphotericin B 3–4 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid for at least 2 weeks, followed by consolidation therapy
Alternative regimen (1): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
Alternative regimen (2): Amphotericin B lipid complex 5 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
Alternative regimen (3): Liposomal Amphotericin B 3-4 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
Alternative regimen (4): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
Alternative regimen (5): Fluconazole 400–800 mg PO or IV qd AND Flucytosine 25 mg/kg PO qid
Alternative regimen (6): Fluconazole 1200 mg PO or IV qd

6.23.1.1.2. Consolidation therapy

Preferred regimen: Fluconazole 400 mg PO (or IV) qd for atleast 8 weeks
Note: Preferred therapy followed by maintenance therapy.
Maintenance therapy: Fluconazole 200 mg PO qd for at least 12 months
Alternative regimen: Itraconazole 200 mg PO bid for 8 weeks

6.23.1.2. Non-CNS cryptococcosis with mild-to-moderate symptoms and focal pulmonary infiltrates

Preferred regimen: Fluconazole, 400 mg PO qd for 12 months
Note: Patients receiving Flucytosine should have either blood levels monitored (peak level 2 hours after dose should be 30–80 mcg/mL) or close monitoring of blood counts for development of cytopenia. Dosage should be adjusted in patients with renal insufficiency.

6.24. Mucocutaneous candidiasis

6.24.1. Treatment

6.24.1.1. For oropharyngeal candidiasis

Oral Therapy

Preferred regimen: Fluconazole 100 mg PO qd for 7-14 days.
Alternative regimen: Itraconazole oral solution 200 mg PO qd for 7-14 days OR Posaconazole oral suspension 400 mg PO bid for 1 day, then 400 mg qd 7-14 days

Topical therapy

Preferred regimen: Clotrimazole troches, 10 mg PO 5 times daily OR Miconazole mucoadhesive buccal 50-mg tablet
Note: Apply to mucosal surface over the canine fossa once daily (do not swallow, chew, or crush).
Alternative regimen: Nystatin suspension 4–6 mL qid or 1–2 flavored pastilles 4– 5 times daily

6.24.1.2. For esophageal candidiasis

Preferred regimen: Fluconazole 100 mg (up to 400 mg) PO or IV qd for 14-21 days OR Itraconazole oral solution 200 mg PO qd for 14-21 days
Alternative regimen (1): Voriconazole 200 mg PO or IV bid for 14-21 days
Alternative regimen (2): Anidulafungin 100 mg IV single dose, then 50 mg IV qd for 14-21 days
Alternative regimen (3): Caspofungin 50 mg IV qd for 14-21 days
Alternative regimen (4): Micafungin 150 mg IV qd for 14-21 days
Alternative regimen (5): Amphotericin B deoxycholate 0.6 mg/kg IV qd for 14-21 days
Alternative regimen (6): Lipid formulation of amphotericin B 3–4 mg/kg IV qd for 14-21 days

6.24.1.3. For uncomplicated vulvo-vaginal candidiasis

Preferred regimen: Oral Fluconazole 150 mg for 1 dose OR Topical azoles (Clotrimazole, Butoconazole, Miconazole, Tioconazole, or Terconazole) for 3– 7 days
Alternative regimen: Itraconazole oral solution 200 mg PO qd for 3–7 days

6.24.1.4. For severe or recurrent vulvovaginal candidiasis

Preferred regimen: Fluconazole 100–200 mg PO qd for ≥7 days OR Topical antifungal ≥7 days

6.25. Bartonellosis

6.25.1. Treatment

6.25.1.1. For bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis

Preferred regimen (1): Doxycycline 100 mg PO or IV q12h for 3 months
Preferred regimen (2): Erythromycin 500 mg PO or IV q6h for 3 months
Alternative regimen (1): Azithromycin 500 mg PO qd
Alternative regimen (2):} Clarithromycin 500 mg PO bid

6.25.1.2. Confirmed bartonella endocarditis

Preferred regimen: Doxycycline 100 mg IV q12h AND Gentamicin 1 mg/kg IV q8h) for 2 weeks, then continue with Doxycycline 100 mg IV or PO q12h
Altered regimen: Doxycycline 100 mg IV AND Rifabutin 300 mg PO or IV q12h for 2 weeks, then continue with Doxycycline 100 mg IV or PI q12h

6.25.1.3. CNS infections

Preferred regimen: (Doxycycline 100 mg with or without Rifabutin 300 mg PO or IV q12h

6.25.1.4. Other severe infections

Preferred regimen (1): Doxycycline 100 mg PO or IV with or without Rifabutin 300 mg PO or IV) q12h for 3 months
Preferred regimen (2): Erythromycin 500 mg PO or IV q6h) with or without Rifabutin) 300 mg PO or IV q12h for 3 months.

Note: If relapse occurs after initial (>3 month) course of therapy, longterm suppression with Doxycycline or a macrolide is recommended as long as CD4 count <200 cells/µL.

6.26. Campylobacteriosis

6.26.1. Treatment

6.26.1.1. For mild-to-moderate disease (If Susceptible)

Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h OR Azithromycin 500 mg PO qd
Alternative regimen: Levofloxacin 750 mg PO or IV q24h OR Moxifloxacin 400 mg (PO or IV) q24h

6.26.1.2. For campylobacter bacteremia

Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h AND an aminoglycoside.
Duration of Therapy:

Gastroenteritis: 7–10 days (5 days with Azithromycin)
Bacteremia: ≥14 days
Recurrent bacteremia: 2–6 weeks.

6.27. Shigellosis

6.27.1. Treatment

Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
Duration of Therapy:

Gastroenteritis: 7–10 days
Bacteremia: ≥14 days
Recurrent Infections: 2–6 weeks

Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h for 5 days
Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h for 5 days
Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h for 5 days
Alternative regimen (4): Azithromycin 500 mg PO qd for 5 days
Note: Antimotility agents should be avoided.

6.28. Salmonellosis

6.28.1. Treatment

Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h
Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h
Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h
Alternative regimen (4): Cefotaxime 1 g IV q8h
Alternative regimen (5): Ceftriaxone 1 g IV q24h
Duration of therapy:

For gastroenteritis without bacteremia:

If CD4 count ≥200 cells/µL: 7–14 days.
If CD4 count <200 cells/µL: 2–6 weeks.

For gastroenteritis with bacteremia:

If CD4 count ≥200/µL: 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
If CD4 count <200 cells/µL: 2–6 weeks

Note (1): The role of long-term secondary prophylaxis in patients with recurrent Salmonella bacteremia is not well established. Must weigh benefit against risks of long-term antibiotic exposure.
Note (2): Secondary Prophylaxis Should Be Considered For:

Patients with recurrent Salmonella gastroenteritis +/- bacteremia.
Patients with CD4 <200 cells/µL with severe diarrhea.

6.29. Bacterial enteric infections

6.29.1. Empiric therapy

Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
Alternative regimen: Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h
Note: Antimotility agents should be avoided if there is concern about inflammatory diarrhea, including Clostridium-difficile-associated diarrhea.

6.30.Bacterial respiratory diseases

6.30.1. Treatment

6.30.1.1. Empiric outpatient therapy

Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
Alternative regimen: Amoxicillin 500 mg PO AND Doxycycline 100mg PO qd
Note: Therapy should be adjusted based on the results of diagnostic workup.

6.30.1.2. For penicillin-allergic patients

Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
Alternative regimen: Aztreonam 1 g IV q24h AND Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

6.30.1.3. Empiric therapy for non-ICU hospitalized patients

Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd

6.30.1.3. Empiric therapy for patients at risk of pseudomonas pneumonia

Preferred regimen: : Piperacillin-Tazobactam 2 g-0.25 g IV q24h AND (Ciprofloxacin 400 mg IV q8–12h OR Levofloxacin 750 mg IV) q24h

6.30.1.4. Empiric therapy for patients at risk for methicillin-resistant staphylococcus aureus pneumonia

Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg) PO AND Linezolid 600 mg (IV or PO).
Note (1): Empiric therapy with a macrolide alone is not routinely recommended, because of increasing pneumococcal resistance.
Note (2): Chemoprophylaxis can be considered for patients with frequent recurrences of serious bacterial pneumonia.

6.31. Cryptosporidiosis

6.31.1. Treatment

Note (1): Initiate or optimize ART for immune restoration to CD4 count >100 cells/µL. Aggressive oral or IV rehydration and replacement of electrolyte loss and symptomatic treatment of diarrhea with anti-motility agents.
Preferred regimen (1): Nitazoxanide 500–1000 mg PO bid for 14 days
Preferred regimen (2): Paromomycin 500 mg PO qid for 14–21 days
Note (2): With optimized anti retroviral therapy, symptomatic treatment and rehydration and electrolyte replacement is recommended. Tincture of opium may be more effective than Loperamide in management of diarrhea.

6.32. Microsporidiosis

6.32.1. Treatment

6.32.1.1. For GI infections caused by enterocytozoon bienuesi

Note: Initiate or optimize anti retroviral therapy as immune restoration to CD4 count >100 cells/µL AND manage severe dehydration, malnutrition, and wasting by fluid support.
Preferred therapy (1): Fumagillin 60 mg/day PO bid
Preferred therapy (2): TNP-470 PO bid
Preferred therapy (3): Nitazoxanide 1000 mg PO bid

6.32.1.2. For intestinal and disseminated (not ocular) infections caused by microsporidia other than E. bienuesi and vittaforma corneae

Preferred regimen: Albendazole 400 mg PO bid, continue until CD4 count >200 cells/µL for >6 months after initiation of anti retroviral therapy
Alternative regimen: Itraconazole 400 mg PO qd AND Albendazole 400 mg PO bid

6.32.1.3. For ocular infection

Preferred regimen: Topical fumagillin bicylohexylammonium (Fumidil B) eye drops: 3 mg/mL in saline (fumagillin 70 µg/mL)—2 drops q2h for 4 days, then 2 drops qid AND Albendazole 400 mg PO bid, for management of systemic infection
Note: Therapy should be continued until resolution of ocular symptoms and CD4 count increase to >200 cells/µL for >6 months in response to anti retroviral therapy.

6.33. Progressive Multifocal Leukoencephalopathy (PML)

Note (1): There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.
Note (2): Initiate anti retroviral therapy immediately in anti retroviral therapy naive patients.
Note (3): Optimize anti retroviral therapy in patients who develop PML in phase of HIV viremia on anti retroviral therapy.
Note (4): Corticosteroids may be used for PML-IRIS characterized by contrast enhancement, edema or mass effect, and with clinical deterioration.

References

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↑ ^2.0 ^2.1 Baddour, LM.; Wilson, WR.; Bayer, AS.; Fowler, VG.; Bolger, AF.; Levison, ME.; Ferrieri, P.; Gerber, MA.; Tani, LY. (2005). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): e394–434. doi:10.1161/CIRCULATIONAHA.105.165564. PMID 15956145. Unknown parameter |month= ignored (help)
↑ "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association".
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↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association".
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Tunkel, Allan R.; Hartman, Barry J.; Kaplan, Sheldon L.; Kaufman, Bruce A.; Roos, Karen L.; Scheld, W. Michael; Whitley, Richard J. (2004-11-01). "Practice guidelines for the management of bacterial meningitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (9): 1267–1284. doi:10.1086/425368. ISSN 1537-6591. PMID 15494903.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Kasper, Dennis (2015). Harrison's principles of internal medicine. New York: McGraw Hill Education. ISBN 978-0071802154.
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↑ Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910.
↑ Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910.
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↑ Curtin-Wirt C, Casey JR, Murray PC, Cleary CT, Hoeger WJ, Marsocci SM; et al. (2003). "Efficacy of penicillin vs. amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis". Clin Pediatr (Phila). 42 (3): 219–25. PMID 12739920.
↑ Pichichero ME (2005). "A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients". Pediatrics. 115 (4): 1048–57. doi:10.1542/peds.2004-1276. PMID 15805383.
↑ WANNAMAKER LW, RAMMELKAMP CH, DENNY FW, BRINK WR, HOUSER HB, HAHN EO; et al. (1951). "Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin". Am J Med. 10 (6): 673–95. PMID 14837911.
↑ Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH, Infectious Diseases Society of America (2002). "Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America". Clin Infect Dis. 35 (2): 113–25. doi:10.1086/340949. PMID 12087516.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "group B Streptococcus infections".
↑ "group B Streptococcus infections".
↑ Mukhopadhyay S, Dukhovny D, Mao W, Eichenwald EC, Puopolo KM (2014). "2010 perinatal GBS prevention guideline and resource utilization". Pediatrics. 133 (2): 196–203. doi:10.1542/peds.2013-1866. PMC 3904275. PMID 24446442.
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↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
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↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
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↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
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↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ "The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America" (PDF).
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Lua error: expandTemplate: template "citation error" does not exist.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Mukara, B. K.; Munyarugamba, P.; Dazert, S.; Löhler, J. (2014-07). "Rhinoscleroma: a case series report and review of the literature". European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 271 (7): 1851–1856. doi:10.1007/s00405-013-2649-z. ISSN 1434-4726. PMID 23904142. Check date values in: |date= (help)
↑ de Pontual, Loïc; Ovetchkine, Philippe; Rodriguez, Diana; Grant, Audrey; Puel, Anne; Bustamante, Jacinta; Plancoulaine, Sabine; Yona, Laurent; Lienhart, Pierre-Yves; Dehesdin, Danièle; Huerre, Michel; Tournebize, Régis; Sansonetti, Philippe; Abel, Laurent; Casanova, Jean Laurent (2008-12-01). "Rhinoscleroma: a French national retrospective study of epidemiological and clinical features". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (11): 1396–1402. doi:10.1086/592966. ISSN 1537-6591. PMID 18947330.
↑ Gaafar, Hazem A.; Gaafar, Alaa H.; Nour, Yasser A. (2011-04). "Rhinoscleroma: an updated experience through the last 10 years". Acta Oto-Laryngologica. 131 (4): 440–446. doi:10.3109/00016489.2010.539264. ISSN 1651-2251. PMID 21198342. Check date values in: |date= (help)
↑ Mukara, B. K.; Munyarugamba, P.; Dazert, S.; Löhler, J. (2014-07). "Rhinoscleroma: a case series report and review of the literature". European archives of oto-rhino-laryngology: official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS): affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 271 (7): 1851–1856. doi:10.1007/s00405-013-2649-z. ISSN 1434-4726. PMID 23904142. Check date values in: |date= (help)
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "TYPHOID FEVER".
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" (PDF).
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae type 1" (PDF).
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ "WHO. Cholera Outbreak: Assessing the Outbreak Response and Improving Preparedness" (PDF).
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↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ "q fever".
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
↑ Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
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↑ Kauffman, C. A.; Bustamante, B.; Chapman, S. W.; Pappas, P. G. (2007). "Clinical Practice Guidelines for the Management of Sporotrichosis: 2007 Update by the Infectious Diseases Society of America". Clinical Infectious Diseases. 45 (10): 1255–1265. doi:10.1086/522765. ISSN 1058-4838.
↑ "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents".
↑ "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents".
↑ "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents".
↑ Treatment of tuberculosis guidelines. Geneva: World Health Organization. 2010. ISBN 9789241547833.
↑ "The use of delamanid in the treatment of multidrug-resistant tuberculosis" (PDF).
↑ "WHO".
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ American Thoracic Society. CDC. Infectious Diseases Society of America (2003). "Treatment of tuberculosis". MMWR Recomm Rep. 52 (RR-11): 1–77. PMID 12836625.
↑ Griffith, Daviday E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richarday J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, anday prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory anday Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. Unknown parameter |pmiday= ignored (help)
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Tortoli, E.; Besozzi, G.; Lacchini, C.; Penati, V.; Simonetti, M. T.; Emler, S. (1998-04). "Pulmonary infection due to Mycobacterium szulgai, case report and review of the literature". The European Respiratory Journal. 11 (4): 975–977. ISSN 0903-1936. PMID 9623706. Check date values in: |date= (help)
↑ Griffith, David E.; Aksamit, Timothy; Brown-Elliott, Barbara A.; Catanzaro, Antonino; Daley, Charles; Gordin, Fred; Holland, Steven M.; Horsburgh, Robert; Huitt, Gwen; Iademarco, Michael F.; Iseman, Michael; Olivier, Kenneth; Ruoss, Stephen; von Reyn, C. Fordham; Wallace, Richard J.; Winthrop, Kevin; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America (2007-02-15). "An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–416. doi:10.1164/rccm.200604-571ST. ISSN 1073-449X. PMID 17277290.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Rossignol JF, Ayoub A, Ayers MS (2001). "Treatment of diarrhea caused by Cryptosporidium parvum: a prospective randomized, double-blind, placebo-controlled study of Nitazoxanide". J Infect Dis. 184 (1): 103–6. doi:10.1086/321008. PMID 11398117.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Smith HV, Corcoran GD (2004). "New drugs and treatment for cryptosporidiosis". Curr Opin Infect Dis. 17 (6): 557–64. PMID 15640710.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Template:Citeweb
↑ Gilbert, David (2014). The Sanford guide to antimicrobial therapy 2014. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808782.
↑ Nagata, Noriyuki; Marriott, Deborah; Harkness, John; Ellis, John T.; Stark, Damien (2012-12). "Current treatment options for Dientamoeba fragilis infections". International Journal for Parasitology. Drugs and Drug Resistance. 2: 204–215. doi:10.1016/j.ijpddr.2012.08.002. ISSN 2211-3207. PMC 3862407. PMID 24533282. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ "CDC Parasites - Giardia".
↑ Gardner TB, Hill DR (2001). "Treatment of giardiasis". Clin Microbiol Rev. 14 (1): 114–28. doi:10.1128/CMR.14.1.114-128.2001. PMC 88965. PMID 11148005.CS1 maint: PMC format (link)
↑ "CDC - Cystoisosporiasis".
↑ "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" (PDF).
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Visvesvara, Govinda S.; Moura, Hercules; Schuster, Frederick L. (2007-06). "Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea". FEMS immunology and medical microbiology. 50 (1): 1–26. doi:10.1111/j.1574-695X.2007.00232.x. ISSN 0928-8244. PMID 17428307. Check date values in: |date= (help)
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Marciano-Cabral, Francine; Cabral, Guy (2003-04). "Acanthamoeba spp. as agents of disease in humans". Clinical Microbiology Reviews. 16 (2): 273–307. ISSN 0893-8512. PMC 153146. PMID 12692099. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.
↑ Visvesvara, Govinda S.; Moura, Hercules; Schuster, Frederick L. (2007-06). "Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea". FEMS immunology and medical microbiology. 50 (1): 1–26. doi:10.1111/j.1574-695X.2007.00232.x. ISSN 0928-8244. PMID 17428307. Check date values in: |date= (help)
↑ "Acanthamoeba Keratitis Fact Sheet (CDC)".
↑ "Balamuthia mandrillaris - Granulomatous Amebic Encephalitis (CDC)".
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Template:Citeweb
↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
↑ Template:Citeweb
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↑ "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" (PDF).
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↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ "WGO Practice Guideline Management of Strongyloidiasis" (PDF).
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