Sandbox ID Lower Respiratory Tract

Acute exacerbations of chronic bronchitis

• Acute exacerbation of chronic bronchitis

• 1. Outpatient management

• Patients with only 1 of the 3 cardinal symptoms of COPD (↑ dyspnea, ↑ sputum volume, ↑ sputum purulence) may not benefit from antibiotics
• Preferred regimen (1): Doxycycline 100 mg PO bid for 7-10 days
• Preferred regimen (2): Amoxicillin 875 mg PO bid
• Preferred regimen (3): Amoxicillin 500 mg PO tid
• Preferred regimen (4): Trimethoprim-sulfamethoxazole DS 800/160 mg PO bid for 10-14 days
• Alternative regimen (1): Amoxicillin-clavulanate 875/125 mg PO bid for 10-14 days
• Alternative regimen (2): Levofloxacin 500 mg PO qd for 7-10 days
• Alternative regimen (3): Azithromycin 500 mg PO single dose THEN 250 mg PO qd for 4 days
• Alternative regimen (4): Cefpodoxime 200 mg PO bid for 10 days
• Alternative regimen (5): Amoxicillin-clavulanate 500/125 mg PO tid for 10-14 days
• Alternative regimen (6): Moxifloxacin 400 mg PO qd for 5 days
• Alternative regimen (7): Gemifloxacin 320 mg PO qd for 5 days
• Alternative regimen (8): Clarithromycin 250-500 mg PO bid for 7-14 days
• Alternative regimen (9): Clarithromycin ER 1000 mg PO qd for 14 days
• Alternative regimen (10): Cefprozil 250-500 mg PO bid for 10 days
• Alternative regimen (11): Cefixime 400 mg PO qd for 10 days

• 2. Inpatient management

• Indications for hospital admission:

• Intense symptoms (e.g.: sudden development of resting dyspnea)
• Old age
• Severe underlying COPD
• Cyanosis
• Peripheral edema
• Serious comorbidities (e.g.: HF, Afib, renal failure)
• Failure of outpatient treatment
• Frequent exacerbations
• Insufficient home support

• 2.1 Treatment of acute exacerbation of chronic bronchitis, when pseudomonas infection not suspected

• Preferred regimen (1): Moxifloxacin 400 mg IV q24h for 5 days
• Preferred regimen (2): Levofloxacin 500 mg IV q24h for 7-10 days

• 2.2 Treatment of acute exacerbation of chronic bronchitis, when pseudomonas infection is suspected

• Preferred regimen (1): Ceftazidime 30-50 mg/kg IV q8hr (maximum dose 6 g/day)
• Preferred regimen (2): Piperacillin-Tazobactam 3.375 g IV q6h for 7-10 days
• Preferred regimen (3): Cefepime 1-2 g IV q8-12hr for 7-10 days (extend to 21 days if culture positive for Pseudomonas)
• Alternative regimen (1): Ceftriaxone 1-2 g IV/IM q12-24h for 4-14 days
• Alternative regimen (2): Ceftriaxone 1-2 g IV/IM q8h for 4-14 days

Bronchiectasis

• Bronchiectasis

• 1. Acute exacerbations of bronchiectasis

• 1.1 Empiric antimicrobial therapy

• Preferred regimen: Amoxicillin 0.5-1 g PO/IV q8h for 14 days
• Alternative regimen (1): Ciprofloxacin 500-750 mg PO bid for 14 days
• Alternative regimen (2): Clarithromycin 500 mg PO bid for 14 days

• 1.2 Pathogen-directed antimicrobial therapy

• 1.2.1 Streptococcus pneumoniae

• Preferred regimen: Amoxicillin 500 mg PO tid for 14 days
• Alternative regimen: Clarithromycin 500 mg PO bid for 14 days

• 1.2.2 Haemophilus influenzae (b-lactamase negative)

• Preferred regimen (1): Amoxicillin 0.5-1 g PO tid for 14 days
• Preferred regimen (2): Amoxicillin 3 g PO bid for 14 days
• Alternative regimen (1): Clarithromycin 500 mg PO bid for 14 days
• Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 14 days
• Alternative regimen (3): Ceftriaxone 2 g IV q24h for 14 days

• 1.2.3 Haemophilus influenzae (b-lactamase positive)

• Preferred regimen: Amoxicillin-Clavulanate 625 mg PO tid for 14 days
• Alternative regimen (1): Clarithromycin 500 mg PO bid for 14 days
• Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 14 days
• Alternative regimen (3): Ceftriaxone 2 g IV q24h for 14 days

• 1.2.4 Moraxella catarrhalis

• Preferred regimen: Amoxicillin-Clavulanate 625 mg PO tid for 14 days
• Alternative regimen: Ciprofloxacin 500 mg PO bid for 14 days

• 1.2.5 Staphylococcus aureus (MSSA)

• Preferred regimen: Flucloxacillin 500 mg PO qid for 14 days
• Alternative regimen: Clarithromycin 500 mg PO bid 14 days

• 1.2.6 Staphylococcus aureus (MRSA) (mild-to-moderate)

• Preferred regimen (weight < 50 kg): Rifampicin 450 mg PO qd AND Trimethoprim 200 mg PO bid for 14 days
• Preferred regimen (weight > 50 kg): Rifampicin 600 mg PO qd AND Trimethoprim 200 mg PO bid for 14 days
• Alternative regimen (weight < 50 kg): Rifampicin 450 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
• Alternative regimen (weight > 50 kg): Rifampicin 600 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
• Alternative regimen: Linezolid 600 mg PO bid for 14 days (third-line therapy)

• 1.2.7 Staphylococcus aureus (MRSA) (severe)

• Preferred regimen (1): Vancomycin 1 g IV q12h (trough levels of 10-20 ng/mL)
• Preferred regimen (2): Teicoplanin 400 mg IV q24h for 14 days
• Alternative regimen: Linezolid 600 mg IV q12h for 14 days

• 1.2.8 Coliforms (eg, Klebsiella, enterobacter)

• Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
• Alternative regimen: Ceftriaxone 2 g IV od 14 days

• 1.2.9 Pseudomonas aeruginosa

• Preferred regimen: Ciprofloxacin 500-750 mg PO bid for 14 days
• Alternative regimen (1): Ceftazidime 2 g PO tid for 14 days
• Alternative regimen (2): Piperacillin-Tazobactam 4.5 g PO tid for 14 days
• Alternative regimen (3): Aztreonam 2 g PO tid for 14 days
• Alternative regimen (4): Meropenem 2 g PO tid for 14 days

• 1.2.10 Pediatric Dosing

• Amoxicillin 20-50 mg/kg/day PO bid or tid
• Co-amoxiclav 20-45 mg/kg/day PO bid or tid
• Trimethoprim 4-6 mg/kg/day PO bid (Children < 12 yr)
• Trimethoprim 100-200 mg PO bid (Children > 12 yr)
• Rifampicin 450 mg PO qd (weight < 50 kg)
• Rifampicin 600 mg PO qd (weight > 50 kg)
• Vancomycin 45-60 mg/kg/day IV q8-12h
• Ciprofloxacin 15-30 mg/kg/day PO/IV q12h
• Doxycycline 2-5 mg/kg/day PO/IV q12-24h (maximum daily dose: 200 mg)
• Linezolid 10 mg/kg IV/PO q12h
• Ceftriaxone 50-75 mg/kg IV/IM q24h
• Ceftazidime 150 mg/kg/day IV/IM q8h

• 2. Long-term antibiotic prophylaxis
• Patients with ≥3 exacerbations/year requiring antibiotic therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long-term antibiotic prophylaxis

• 2.1 Pathogen-directed antimicrobial therapy

• 2.1.1 Streptococcus pneumoniae

• Preferred regimen: Amoxicillin 500 mg PO bid
• Alternative regimen: Clarithromycin 250 mg PO bid

• 2.1.2 Haemophilus influenzae (b-lactamase negative)

• Preferred regimen: Amoxicillin 500 mg PO bid
• Alternative regimen: Clarithromycin 250 mg PO bid

• 2.1.3 Haemophilus influenzae (b-lactamase positive)

• Preferred regimen: Amoxicillin-Clavulanate 375 mg PO tid
• Alternative regimen: Clarithromycin 250 mg PO bid

• 2.1.4 Moraxella catarrhalis

• Preferred regimen: Amoxicillin-Clavulanate 375 mg PO tid
• Alternative regimen: Clarithromycin 250 mg PO bid

• 2.1.5 Staphylococcus aureus (MSSA)

• Preferred regimen: Flucloxacillin 500 mg PO bid
• Alternative regimen: Clarithromycin 250 mg PO bid

• 3. Pseudomonas eradication (colonization)

• 3.1 Initial therapy

• Preferred regimen: Ciprofloxacin 750 mg PO bid for 14 days

• 3.2 Secondary therapy in case of treatment failure

• Preferred regimen (1): Piperacillin-tazobactam 4.5 g PO tid for 14 days
• Preferred regimen (2): Cefepime 1-2 g IV q8-12h
• Preferred regimen (3): Ciprofloxacin 750 mg PO bid for 4 weeks AND Colistin (Nebulized) 2 MU NEB bid for 3 months
• Preferred regimen (3): Colistin (Nebulized) 2 MU NEB bid for 3 months

Bronchiolitis

• Bronchiolitis

• 1. Treatment

• Preferred regimen: Supportive care. No antimicrobial therapy recommended.

• 2. Prophylaxis

• Indications for prophylaxis:

• First year of life during RSV season in infants with hemodynamically significant heart disease
• First year of life during RSV season in preterm infants < 32 weeks 0 days’ gestation who require > 21% oxygen for at least the first 28 days of life

• Preferred regimen: Palivizumab 15 mg/kg IM monthly for 5 months

Bronchitis

• Acute bronchitis

• 1.Treatment of acute bronchitis with no suspicion of pertussis

• Preferred regimen: Supportive care. Antimicrobial therapy not recommended.

• 2.Treatment of acute bronchitis with suspected or confirmed pertussis

• Preferred regimen (1): Erythromycin 15 mg/kg PO tid for 5-14 days
• Preferred regimen (2): Azithromycin 500 mg PO single dose THEN Azithromycin 250 mg PO qd for 4 days

Cystic fibrosis

• Cystic Fibrosis

• 1.Pathogen-directed antimicrobial therapy

• 1.1 Pseudomonas aeruginosa

• 1.1.1 Adults

• Preferred regimen (1): Tobramycin 3.3 mg/kg PO tid OR Tobramycin 12 mg/kg IV q24h AND (Piperacillin 100 mg/kg PO qid
• Preferred regimen (2): Ticarcillin 100 mg/kg PO qid
• Preferred regimen (3): Ceftazidime 50 mg/kg IV q8h (to maximum of 6 g/day)
• Alternative regimen (1): (Tobramycin 3.3 mg/kg PO tid OR Tobramycin 12 mg/kg IV q24h) AND Aztreonam 50 mg/kg IV q8h
• Alternative regimen (2): (Tobramycin 3.3 mg/kg PO tid OR Tobramycin 12 mg/kg IV q24h) AND Imipenem 15-25 mg/kg IV q6h
• Note: If Tobramycin resistant add Ciprofloxacin 500-750 mg PO bid for 7-14 days OR Ciprofloxacin 400 mg IV q12h for 7-14 days OR Levofloxacin 750 mg PO qd for 7-14 days

• 1.1.2 Children

• Preferred regimen: (Ciprofloxacin 500-750 mg PO bid for 7-14 days OR Ciprofloxacin 400 mg IV q12h for 7-14 days) AND Ceftazidime 0.5-1 g IV q8h

• 1.2 Staphylococcus aureus

• 1.2.1 Adults

• 1.2.1.1 Methicillin sensitive staphylococcus aureus

• Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h

• 1.2.1.2 Methicillin resistant staphylococcus aureus

• Preferred regimen: Vancomycin 15-20 mg/kg IV q8-12h OR Linezolid 600 mg PO/IV q12h

• 1.2.2 Children

• 1.2.2.1 Methicillin sensitive staphylococcus aureus

• Preferred regimen: Nafcillin 5 mg/kg IV q6h (age > 28 days) OR Oxacillin 75 mg/kg IV q6h (age > 28 days)

• 1.2.2.2 Methicillin resistant staphylococcus aureus

• Preferred regimen: Vancomycin 40 mg/kg IV divided q6-8h (age >28 days) OR Linezolid 10 mg/kg PO/IV q8h (up to age 12)

• 1.3 Burkholderia cepacia

• Preferred regimen: Trimethoprim-sulfamethoxazole 5/25 mg/kg IV q6h
• Alternative regimen: Chloramphenicol 15–20 mg/kg PO/IV q6h

Empyema

• Empyema

• 1. Empiric antimicrobial therapy or culture negative therapy

• Causative pathogens:

• Streptococcus milleri
• Streptococcus pneumoniae
• Streptococcus intermedius
• Staphylococcus aureus
• Enterobacteriaceae
• Escherichia coli
• Fusobacterium spp.
• Bacteroides spp.
• Peptostreptococcus spp.

• Preferred regimen (1): Cefuroxime 1.5 g IV q8h AND Metronidazole 500 mg IV q8h
• Preferred regimen (2): Ceftriaxone 1.5 g IV q8h AND Metronidazole 500 mg IV q8h
• Preferred regimen (3): Piperacillin-Tazobactam 3.375 g IV q4h OR Ticarcillin-clavulanate 3.1 g IV q4h OR Ampicillin-Sulbactam 2/1 g IV q6h
• Preferred regimen (4): Meropenem 1 g IV q8h OR Imipenem 500 mg IV q6h
• Note: Consider coverage for MRSA if high suspicion exists.

• 2. Pathogen-based therapy

• 2.1 Acute empyema

• 2.1.1 Streptococcus pneumoniae, Group A streptrococcus

• Preferred regimen: Ceftriaxone 1.5 g IV/IM q24h

• 2.1.2 Staphylococcus aureus

• 2.1.2.1 MSSA

• Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h

• 2.1.2.2 MRSA

• Preferred regimen: Vancomycin 1 g IV q12h OR Linezolid 600 mg PO/IV q12h

• 2.1.3 Hemophilus influenzae

• Preferred regimen: Ceftriaxone 1.5 g IV/IM q24h
• Alternative regimen: Trimethoprim-Sulfamethoxazole 8-20 mg TMP/kg/day IV q6-12h or Ampicillin-Sulbactam 2/1 g IV q6h

• 2.2 Subacute/chronic empyema

• 2.2.1 Anaerobic streptococcus, Streptococcus milleri, Bacteroides species, Enterobacteriaceae, Mycobacterium tuberculosis

• Preferred regimen: Clindamycin 450–900 mg IV q8h AND Ceftriaxone 1.5 g IV/IM q24h
• Alternative regimen: Imipenem 500 mg IV q6h OR Piperacillin-Tazobactam 3.375 g IV q4h OR Ticarcillin-clavulanate 3.1 g IV q4h OR Ampicillin-Sulbactam 2/1 g IV q6h

Pneumonia

• Pneumonia

• 1. Community-acquired pneumonia

• 1.1 Empiric therapy in adults

• 1.1.1 Outpatient treatment

• 1.1.1.1 Previously healthy and no use of antimicrobials within the previous 3 months

• Preferred regimen (1): (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR Azithromycin 500 mg IV single dose
• Preferred regimen (2): Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days
• Preferred regimen (3): Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)
• Alternative regimen: Doxycycline 100 mg PO/IV q12h

• 1.1.1.2 Presence of comorbidities, use of immunosuppressing drugs, or use of antimicrobials within the previous 3 months

• Preferred regimen (1): Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days OR Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR Gemifloxacin 320 mg PO qd for 5 or 7 days
• Preferred regimen (2): (Amoxicillin 1 g PO q8h OR Amoxicillin-clavulanate 1-2 g PO bid OR Ceftriaxone 1-2 g IV q24h OR Cefpodoxime 200 mg PO bid for 14 days OR Cefuroxime 750 mg IM/IV q8h) AND either (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR (Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days) OR Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)
• Note: In the case of recent (past 3 months) antimicrobial therapy, an alternative from a different class should be selected.

• 1.1.2 Inpatient treatment

• 1.1.2.1 Non-ICU treatment

• Preferred regimen (1): Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO qd for 5-7 days
• Preferred regimen (2): (Amoxicillin 1 g PO q8h OR Amoxicillin-clavulanate 1-2 g PO bid OR Ceftriaxone 1-2 g IV q24h OR Cefpodoxime 200 mg PO bid for 14 days OR Cefuroxime 750 mg IM/IV q8h) AND either (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days) OR (Clarithromycin 250 mg PO bid for 7-14 days OR Clarithromycin 1000 mg PO qd for 7 days) OR Erythromycin 250-500 mg PO bid or tid (maximum daily dose 4 g)

• 1.1.2.2 ICU treatment

• Preferred regimen (1): (Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1-2 g IV q24h OR Ampicillin-sulbactam 1.5-3 g IV q6h) AND (Levofloxacin 500 mg IV q24h for 7-14 days OR Levofloxacin 750 mg IV q24h for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO q24h for 5-7 days)
• Alternative regimen (1): (Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1-2 g IV q24h OR Ampicillin-sulbactam 1.5-3 g IV q6h) AND (Azithromycin 500 mg IV qd for 2 days (PO for a total of 7-10 days)
• Alternative regimen (2): Aztreonam 2 g IV q6-8h (maximum daily dose 8 g) AND (Levofloxacin 500 mg IV q24h for 7-14 days OR Levofloxacin 750 mg IV q24h for 5 days OR Moxifloxacin 400 mg IV q24h for 7-14 days OR Gemifloxacin 320 mg PO q24h for 5-7 days)

• 1.1.3 Special considerations

• 1.1.3.1 Suspected Pseudomonas

• Preferred regimen (1): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (2): Cefepime 1-2 g IV q8-12h for 7-10 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (3): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (4): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (5): Cefepime AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (6): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Azithromycin 500 mg PO single dose for 1 day THEN 250 mg PO qd for 4 days)
• Preferred regimen (7): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days)
• Preferred regimen (8): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 7-14 days AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (9): Cefepime 1-2 g IV q8-12h for 7-10 days AND (Amikacin 20 mg/kg/day IV q8-12h OR Gentamicin 3-5 mg/kg/day IV/IM q8h OR Tobramycin 3-6 mg/kg/day IV/IM q8h) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg IV qd for 7-14 days OR Levofloxacin 750 mg IV qd for 5 days)
• Preferred regimen (10): (Imipenem 500 mg IV q6h for ≤5 days OR Meropenem 500 mg IV q8hr for ≤5 days) AND (Ciprofloxacin 400 mg IV q8h for 7-14 days OR Levofloxacin 500 mg PO qd for 7-14 days OR Levofloxacin 750 mg PO qd for 5 days)
• Note: For penicillin-allergic patients, substitute the beta-lactam for Aztreonam 1-2 g IV q6-8h.

• 1.1.3.2 Suspected methicillin resistant Staphylococcus aureus (add the following)

• Preferred regimen: Vancomycin 45-60 mg/kg/day divided q8-12h OR Linezolid 600 mg PO/IV q12h for 10-14 days

• 1.1.3.3 Neutropenic patient

• 1.1.3.3.1 No risk for multi-drug resistance

• Preferred regimen: Ceftriaxone 1-2 g q24h IV or IM (max: 4 g/day) OR Levofloxacin 750 mg q24h for 7-14 days OR Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR Ciprofloxacin 400 mg PO q8h for 10-14 days OR Ampicillin sulbactam 1-2 g q6-8h IV/IM (maximum: 8 g/day) OR Ertapenem 1 g IM/IV q24h for 10-14 days.

• 1.1.3.3.2 Risk for multi drug resistance

• Preferred Regimen: (Cefepime 1-2 g q8-12h OR Ceftazidime 2 g q8h OR Imipenem 500 mg q6h or 1g q8h OR Meropenem 1 g q8h OR Piperacillin-tazobactam 4.5 g q6h) AND (Ciprofloxacin 400 mg q8h OR Levofloxacin 750 mg q24h OR Amikacin 20 mg/kg per day OR Gentamycin 7 mg/kg per day OR Tobramycin 7 mg/kg per day) AND (Linezolid 600 mg q12h OR Vancomycin 15 mg/kg q12h).
• Note (1) : Trough levels for Gentamycin and Tobramycin should be less than 1 g/ml, and for Amikacin they should be less than 4-5 g/ml.
• Note (2) : Trough levels for Vancomycin should be 15-20 g/ml
• Note (3) : Hospital or community acquired, neutropenic patient (<500 neutrophils per mm3) Vancomycin not included in initial therapy unless high suspicion of infected intravenous access or drug-resistant Streptococcus pneumonia. Amphotericin not used unless still febrile after 3 days or high clinical likelihood.

• 1.2 Pathogen-directed antimicrobial therapy

• 1.2.1 Bacterial pathogens

• 1.2.1.1 Streptococcus pneumoniae

• 1.2.1.1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mg/mL)

• Preferred regimen : Penicillin G 2-3 million units IV q4h OR Amoxicillin 875 mg PO q12h or 500 mg q8h
• Alternative regimen : Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Cefpodoxime 200 mg PO q12h for 14 days OR Cefprozil 500 mg PO q12h for 10 days OR Cefuroxime 750 mg PO/IV q8h OR Cefdinir 300 mg PO q12h for 10 days OR Cefditoren 400 mg PO q12h for 14 day OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Cefotaxime 1 g IM/IV q12h OR Clindamycin 150-450 mg PO q6-8h (maximum: 1800 mg/day) OR Clindamycin 1.2-2.7 g/day IM/IV in 2-4 divided doses (maximum:4800 mg/day) OR Doxycycline 100 mg PI/IV q12h ORLevofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 1.2.1.1.2 Penicillin resistant (minimum inhibitory concentration > 2 mg/mL)

• Preferred regimen (Agents chosen on the basis of susceptibililty) : Cefotaxime 1 g IM/IV q12h OR Ceftriaxone 1 g IV q24h, 2 g daily for patients at risk OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
• Alternative regimen: Vancomycin 45-60 mg/kg/day divided q8-12h (maximum: 2000 mg/dose) for 7-21 days depending on severity OR Linezolid 600 mg PO/IV q12h for 10-14 days OR Amoxicillin 875 mg PO q12h or 500 mg q8 ( 3 g/day with penicillin ,minimum inhibitory concentration 4 ≤ microgram / mL)

• 1.2.1.2 Haemophilus influenzae

• 1.2.1.2.1 Non-beta lactamase producing

• Preferred regimen: Amoxicillin 875 mg PO q12h or 500 mg q8h
• Alternative regimen : Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Doxycycline 100 mg PO/IV q12h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h on days 2-5 OR Clarithromycin 250 mg q12h for 7-14 days or 1000 mg q24h for 7 days

• 1.2.1.2.2 Beta lactamase producing

• Preferred regimen: 2nd or 3rd Generation Cephalosporin OR Amoxicillin-clavulanate 2 g q12h
• Alternative regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Doxycycline 100 mg PO/IV q12h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h on days 2-5 OR Clarithromycin 250 mg q12h for 7-14 days or 1000 mg q24h for 7 days

• 1.2.1.2 Bacillus anthracis (inhalational)

• Preferred Regimen :Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 500 mg q24h for 7-14 days or 750 mg q24h for 5 days OR Doxycycline 100 mg PO/IV q12h
• Alternate Regimen : Other Fluoroquinolones OR B-lactam (if susceptible) OR Rifampin 600 mg PO/IV q24h for 4 days OR Clindamycin 150-450 mg PO q6-8h OR Chloramphenicol 50-100 mg/kg/day IV in divided q6h

• 1.2.1.3 Enterobacteriaceae

• Preferred Regimen: 3rd generation cephalosporin OR Carbapenem- (Imipenem-Cilastatin, OR Meropenem, OR Ertapenem) (drug of choice if extended-spectrum b-lactamase producer)
• Alternate Regimen : b-Lactam / b-lactamase inhibitor- (Piperacillin-Tazobactam for gram-negative bacilli, OR Ticarcillin-Clavulanate OR Ampicillin-Sulbactam OR Amoxicillin-Clavulanate) OR (Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h)

• 1.2.1.4 Pseudomonas aeruginosa

• Preferred Regimen: (Ticarcillin 200-300 mg/kg/day in divided doses q4-6h (maximum: 18 g/day) OR Piperacillin 6-8 g/day IM/IV (100-125 mg/kg daily) divided q6-12h OR Ceftazidime 500 mg to 1 g q8h OR Cefepime 1-2 g q12h for 10 days OR Aztreonam 2 g IV q6-8h (maximum: 8 g/day) OR Imipenem 500 mg IV q6h OR Meropenem 500 mg IV q8h) AND (Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 750 mg daily OR Aminoglycoside)
• Alternative Regimen: Aminoglycoside AND (Ciprofloxacin 500-750 mg q12h for 7-14 days OR Levofloxacin 750 mg daily)

• 1.2.1.5 Staphylococcus aureus

• 1.2.1.5.1 Methicillin sensitive

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

• 1.2.1.5.2 Methicillin resistant

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

• 1.2.1.6 Klebsiella pneumonia

• 1.2.1.6.1 Resistant to third generation cephalosporins and aztreonam

• Preferred regimen (1): Imipenem 0.5 g IV q6h OR Meropenem 0.5–1 g IV q8h

• 1.2.1.6.2 Klebsiella pneumoniae Carbapenemase producers

• Preferred regimen (1): Colistin (=Polymyxin E).In USA : Colymycin-M 2.5-5 mg/kg per day of base divided into 2-4 doses 6.7-13.3 mg/kg per day of colistimethate sodium (max 800 mg/day). Elsewhere: Colomycin and Promixin ≤60 kg, 50,000-75,000 IU/kg per day IV in 3 divided doses (=4-6 mg/kg per day of colistimethate sodium). >60 kg, 1-2 mill IU IV tid (= 80-160 mg IV tid) OR Polymyxin B (Poly-Rx) 15,000–25,000 units/kg/day divided q12h
• Note (1): some strains which hyperproduce extended spectrum beta-lactamase are primarily resistant to Ticarcillin-Clavulanate, Piperacillin-Tazobactam
• Note (2): Extended spectrum beta-lactamases inactivates all Cephalosporins, beta-lactam/beta-lactamase inhibitor drug activation not predictable; co-resistance to all Fluoroquinolones & often Aminoglycosides.
• Note (3): Can give IM, but need to combine with “caine” anesthetic due to pain.

• 1.2.1.7 Moraxella catarrhalis

• Preferred regimen: Amoxicillin-Clavulanate (Augmentin) 2 tablets po bid ( (or)500/125 mg 1 tablet po tid (or) 875/125 mg 1 tablet po bid) OR Cephalosporins- Cefdinir 300 mg po q12h (or) 600 mg q24h, OR (Cefditoren pivoxil 200–400 mg, 2 tabs po bid,OR Cefpodoxime proxetil 0.1–0.2 g po q12h, OR Cefprozil 500 mg po q12h), OR Cefoxitin 1 g q8h–2 g IV/IM q4h, OR (Cefuroxime 0.75–1.5 g IV/IM q8h,ORCefotaxime 1 g q8–12h to 2 g IV q4h, OR Ceftazidime 1–2 g IV/IM q8–12h) OR Trimethoprim-Sulfamethoxazole Single-strength (SS) is Trimethoprim 80 mg / Sulfamethoxazole 400 mg ,OR (double-strength (DS) Trimethoprim 160 mg /Sulfamethoxazole 800 mg)
• Alternative regimen: Azithromycin 500 mg IV q24h ,OR Clarithromycin 0.5 g po q12h, OR Telithromycin 800 mg po q24h (two 400 mg tabs po q24h).

• 1.2.1.8 Stenotrophomonas maltophilia

• Preferred regimen: Trimethoprim-Sulfamethoxazole Single-strength (SS) tablet is Trimethoprim 80 mg / Sulfamethoxazole 400 mg, double-strength (DS) tablet is Trimethoprim 160 mg / Sulfamethoxazole 800 mg OR IV treatment (base on TMP component): standard 8–10 mg per kg per day divided q6h, q8h, or q12h.
• Alternative regimen: Ticarcillin-Clavulanate 3.1 g IV q4–6h (Ticarcillin 3 g, Clavulanate 0.1 g per vial) AND Aztreonam 1 g IV q6h (or) 2 g IV q8h
• Note (1): Potential synergy with Trimethoprim-Sulfamethoxazole AND Ticarcillin-Clavulanate.
• Note (2): Stenotrophomonas is one of the microorganisms causing hospital-acquired pneumonia usually with mechanical ventilation.

• 1.2.1.9 Bordetella pertussis

• Preferred Regimen:Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
• Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

• 1.2.1.10 Anaerobes (aspiration pneumonia)

• Preferred Regimen: Piperacillin-Tazobactam 3.375 g IV q6h for 7-10 days (For gram-negative bacilli) OR Ticarcillin Clavulanate 200-300 mg/kg/day IV divided q4-6h (max: 18 g/day) OR Ampicillin-Sulbactam 1500-3000 mg IV q6h OR Amoxicillin-Clavulanate 250-500 mg PO q8h or 875 mg q12h OR Clindamycin 150-450 mg PO q6-8h (max: 1800 mg/day)
• Alternative Regimen: Carbapenem -(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem)

• 1.2.1.11 Mycobacterium tuberculosis

• 1.2.1.11.1 Intensive phase

• Preferred Regimen: Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
• Alternative regimen (1): Isoniazid 5 mg/kg/day q24h daily for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day daily for 2 months (maximum: 600 mg / day) AND Ethambutol 5-25 mg/kg daily for 2 months (maximum dose: 1.6 g) AND Pyrazinamide 1000 - 2000 mg / day daily for 2 months.
• Alternative regimen (2): Isoniazid 5 mg/kg/day q24h 3 times per week for 2 months (usual dose: 300 mg/day) AND Rifampin 10 mg/kg/day 3 times per week for 2 months (maximum: 600 mg / day) s AND Ethambutol 5-25 mg/kg (maximum dose: 1.6 g) 3 times per week for 2 months AND Pyrazinamide 1000 - 2000 mg / day 3 times per week for 2 months.

• 1.2.1.11.2 Continuation phase

• Preferred Regimen:Isoniazid 300 mg/day PO daily for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO daily for 4 months (10 mg/kg/day)
• Alternative regimen (1): Isoniazid 300 mg/day PO 3 times per week for 4 months (5 mg/kg/day) AND Rifampicin 600 mg/day PO 3 times per week for 4 months (10 mg/kg/day)

• 1.2.1.12 Yersinisa pestis

• Preferred Regimen: Streptomycin 15 mg/kg/day (max 1 g/day) OR Gentamicin 7 mg/kg/day
• Alternate Regimen: Doxycycline 100 mg PO/IV q12h OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 1.2.1.13 Atypical bacteria

• 1.2.1.13.1 Mycoplasma pneumoniae

• Preferred Regimen:Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Tetracycline Oral: 250-500 mg q6h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 1.2.1.13.2 Chlamydophila pneumoniae

• Preferred Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h OR Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

• 1.2.1.13.3 Legionella spp.

• Preferred Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
• Alternate Regimen: Doxycycline 100 mg PO/IV q12h

• 1.2.1.13.4 Chlamydophila psittaci

• Preferred Regimen: Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h

• 1.2.1.13.5 Coxiella burnetii

• Preferred Regimen: Tetracycline 250-500 mg PO q6h
• Alternate Regimen: Azithromycin 500 mg PO on day 1 followed by 250 mg q24h

• 1.2.1.13.6 Francisella tularensis

• Preferred Regimen: Doxycycline 100 mg PO/IV q12h
• Alternate Regimen: Gentamicin 7 mg/kg/day OR Streptomycin 15 mg/kg/day (maximum: 1 g)

• 1.2.1.13.7 Burkholderia pseudomallei

• Preferred Regimen : Carbapenem -(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem) OR Ceftazidime 0.5-1 g q8h
• Alternate Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h

• 1.2.1.13.8 Acinetobacter species

• Preferred Regimen : Carbapenem-(Imipenem-Cilastatin, OR Meropenem, OR Ertapenem)
• Alternate Regimen: Cephalosporin-Aminoglycoside OR Ampicillin-Sulbactam OR Colistin 2.5-5 mg/kg/day IM/IV divided q6-12h (maximum: 5 mg/kg/day)

• 1.2.1.14 Gram-positive filamentous bacteria

• 1.2.1.14.1 Actinomyces spp.

• Preferred regimen: Penicillin V 1 g po qid 2-6 wk
• Alternative regimen: Tetracycline 500 mg po q 6 h OR Doxycycline 100 mg q 12 h
• Note: Minocycline, Clindamycin, and Erythromycin have also been successful.

• 1.2.1.14.2 Nocardia spp., ,

• 1.2.1.14.2.1 Initial intravenous therapy (induction therapy)

• Preferred regimen: Trimethoprim-Sulfamethoxazole (15 mg/kg/day IV of the trimethoprim component in 2 to 4 divided doses) for at least three to six weeks AND Amikacin (7.5 mg/kg IV q12h) for at least three to six weeks
• Alternative regimen: Imipenem (500 mg IV q6h) AND Amikacin (7.5 mg/kg IV q12h)
• Note (1): If the patient is allergic to Sulfonamides, desensitization should be performed when possible.
• Note (2): If the isolate is susceptible to the third-generation cephalosporins (Ceftriaxone, Cefotaxime), Imipenem can be switched to one of these agents.
• Note (3): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.

• 1.2.1.14.2.2 Oral maintenence therapy

• Preferred regimen: A sulfonamide (eg,Trimethoprim-Sulfamethoxazole 10 mg/kg/day of the trimethoprim component in 2 or 3 divided doses) AND / OR Minocycline (100 mg bd) AND / OR Amoxicillin-Clavulanate (875 mg bd)
• Note (1): Selected patients who clinically improve with induction intravenous therapy and do not have CNS disease may be switched to oral monotherapy (usually after three to six weeks) based upon susceptibility results.
• Note (2): The duration of intravenous therapy varies with the patient's immune status. In immunocompromised patients, maximal tolerated doses should be given intravenously for at least six weeks and until clinical improvement has occurred; in contrast, immunocompetent patients may be successfully treated with a shorter duration of intravenous therapy. Following the intravenous induction phase, patients may be stepped down to oral antibiotics based upon susceptibility studies
• Note (3): Serious pulmonary infection is treated for 6 to 12 months or longer.

• 1.2.2 Viral pathogens

• 1.2.2.1 Influenza virus

• Preferred Regimen: Oseltamivir 75 mg PO q12h for 5 days (initiated within 48 hours of onset of symptoms) OR Zanamivir Two inhalations (10 mg total) q12h for 5 days (Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours)

• 1.2.2.2 Cytomegalovirus

• Preferred regimen (1): Ganciclovir Induction therapy 5 mg/ kg IV every 12 h for normal GFR; maintenance therapy 5 mg/kg IV daily; 1 g orally every 8 h with food.
• Preferred regimen (2): Valganciclovir Induction therapy 900 mg orally every 12 h; maintenance therapy 900 mg daily.
• Alternative regimen (1): Foscarnet Induction therapy 60 mg/ kg every 8 h for 14–21 days or 90 mg/kg every 12 h for 14–21 days; maintenance therapy 90–120 mg/kg per day as a single infusion.
• Alternative regimen (2): Cidofovir Induction therapy 5 mg/ kg per week for 2 weeks, followed by maintenance therapy every 2 weeks.

• 1.2.3 Fungal pathogens

• 1.2.3.1 Coccidioides species

• Preferred Regimen: Itraconazole 200 mg q12h OR Fluconazole 200-400 mg daily for 3-6 month
• Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day
• Note: No therapy is indicated for uncomplicated infection, treat only if complicated infection

• 1.2.3.2 Histoplasmosis

• Preferred Regimen: Itraconazole 200 mg q12h
• Alternative Regimen: Amphotericin B 0.5-0.7 mg/kg/day

• 1.2.3.3 Blastomycosis

• Preferred Regimen: Itraconazole 200 mg q12h
• Alternate Regimen: Amphotericin B 0.5-0.7 mg/kg/day

• 2. Health care-associated pneumonia

• 2.1 Empiric antimicrobial therapy

• 2.1.1 No risk factors for multi drug resistance

• Preferred Regimen : Ceftriaxone 1-2 g q24h IV or IM (max: 4 g/day) OR Levofloxacin 750 mg q24h for 7-14 days OR Moxifloxacin 400 mg PO/IV q24h for 7-14 days OR Ciprofloxacin 400 mg PO q8h for 10-14 days OR Ampicillin sulbactam 1-2 g q6-8h IV/IM (maximum: 8 g/day) OR Ertapenem 1 g IM/IV q24h for 10-14 days.

• 2.1.2 Risk factors for multi drug resistance

• Preferred Regimen: (Cefepime 1-2 g q8-12h OR Ceftazidime 2 g q8h OR Imipenem 500 mg q6h or 1g q8h OR Meropenem 1 g q8h OR Piperacillin-tazobactam 4.5 g q6h) AND (Ciprofloxacin 400 mg q8h OR Levofloxacin 750 mg q24h OR Amikacin 20 mg/kg per day OR Gentamycin 7 mg/kg per day OR Tobramycin 7 mg/kg per day) AND (Linezolid 600 mg q12h OR Vancomycin 15 mg/kg q12h).
• Note (1): Health care-associated pneumonia used to designate large diverse population of patients with many co-morbidities who reside in nursing homes, other long-term care facilities, require home intravenous therapy (or) are dialysis patients. Pneumonia in these patients frequently resembles hospital-acquired pneumonia.
• Note (2): Trough levels for Gentamycin and Tobramycin should be less than 1 g/ml, and for Amikacin they should be less than 4-5 g/ml.
• Note (3): Trough levels for Vancomycin should be 15-20 g/ml.