Anthrax medical therapy: Difference between revisions

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Revision as of 18:39, 21 August 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Medical therapy of anthrax infection includes antibiotic and antitoxin drugs. Uncomplicated cutaneous anthrax is treated with a single oral antimicrobial drug for a duration of 7-10 days for naturally acquired anthrax and 60 days for bioterrorism-related exposure. In case of systemic anthrax without meningitis, the initial treatment should include ≥2 antimicrobial drugs for ≥2 weeks or until the patient is clinically stable, whichever is longer. In case of systemic anthrax with suspected or confirmed meningitis, the initial treatment should include ≥3 antimicrobial drugs for ≥2 weeks or until the patient is clinically stable, whichever is longer. Once patients with systemic illness who were exposed to aerosolized spores have completed initial combination treatment, they should be transitioned to single-agent oral treatment to prevent relapse from surviving B. anthracis spores. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, mechanical ventilation, corticosteroids, procedures, and surgical interventions in certain occasions. An antitoxin should be added to combination antibiotic treatment. Currently there are 2 antitoxins in the CDC Strategic National Stockpile: raxibacumab and Anthrax Immune Globulin Intravenous (AIGIV).^[1]

Medical Therapy

The treatment of anthrax infection includes antibiotic and antitoxin agents. This treatment and postexposure prophylaxis differs from other bacterial infections because anthrax is associated with:^[1]

Production of toxins
Potential antibiotic resistance
Frequent occurrence of meningitis
Presence of latent spores that must be taken into account when selecting post-exposure prophylaxis or a combination of antibiotics for treatment of anthrax

Antimicrobial Regimen

1. Treatment for cutaneous anthrax, without systemic involvement^[2]

Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 7-10 days (regardless of penicillin susceptibility or if susceptibility is unknown)
Preferred regimen (2): Doxycycline 100 mg PO bid for 7-10 days (regardless of penicillin susceptibility or if susceptibility is unknown)
Preferred regimen (3): Levofloxacin 750 mg PO qd for 7-10 days (regardless of penicillin susceptibility or if susceptibility is unknown)
Preferred regimen (4): Moxifloxacin 400 mg PO qd for 7-10 days (regardless of penicillin susceptibility or if susceptibility is unknown)
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^[2]

2.1 Systemic anthrax with possible/confirmed meningitis
Treatment is with a combination of Bactericidal agent (fluoroquinolone) AND Bactericidal agent (ß-lactam) AND Protein synthesis inhibitor

2.1.1 Bactericidal agent (fluoroquinolone)

Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2-3 weeks
Alternative regimen (1): Levofloxacin 750 mg IV q24h for 2-3 weeks
Alternative regimen (2): Moxifloxacin 400 mg IV q24h for 2-3 weeks

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
Alternative regimen (1): Imipenem 1 g IV q6h for 2-3 weeks
Alternative regimen (2): Doripenem 500 mg IV q8h for 2-3 weeks
Alternative regimen (3): Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) for 2-3 weeks
Alternative regimen (4): Ampicillin 3 g IV q6h (for penicillin-susceptible strains) for 2-3 weeks

2.1.3 Protein synthesis inhibitor

Preferred regimen (1): Linezolid 600 mg IV q12h for 2-3 weeks
Alternative regimen (1): Clindamycin 900 mg IV q8h for 2-3 weeks
Alternative regimen (2): Rifampin 600 mg IV q12h for 2-3 weeks
Alternative regimen (3): 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

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 ^[3]

3.1.1.1 A 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

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

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

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

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

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 ^[4]

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

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

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 weeks
If patients age is 2-5 years: Moxifloxacin 10 mg/kg/day IV divided q1h (not to exceed 200 mg/dose) for 2–3 weeks
If patients age is 6–11 years: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 weeks
If patients age is 12–17 years, = 45 kg body weight: Moxifloxacin 400 mg IV q24h for 2–3 weeks
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 weeks

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 weeks
Preferred regimen (2): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 2–3 weeks
Preferred regimen (3): Doripenem 120 mg/kg/day IV divided q8h (not to exceed 1 g/dose) for 2–3 weeks
Preferred regimen (4): Vancomycin 60 mg/kg/day IV divided q8h for 2–3 weeks

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

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

Preferred regimen (2): Clindamycin 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 2–3 weeks
Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 2–3 weeks
Preferred regimen (4): Chloramphenicol 100 mg/kg/day IV divided q6h for 2–3 weeks

Note (1): Duration of therapy for 2–3 weeks 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

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 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 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

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

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 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

3.2.5.1.2.1.2 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

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 week
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 weeks 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 weeks
Preferred regimen (2): Linezolid 20 mg/kg/day IV divided q12h for 2–3 weeks
Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks

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 weeks
Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age

Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks

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 weeks
Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 weeks
Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks

For 1–4 week of age :

Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 weeks
Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 weeks
Note: Duration of therapy for 2–3 weeks, 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^[2]

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^[4]

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

Antitoxins

An antitoxin should be added to combination antibiotic treatment for any patient for whom there is a high level of clinical suspicion for systemic anthrax. Given that systemic anthrax has a high case-fatality rate and the risk for antitoxin treatment appears to be low, the potential benefit achieved by adding antitoxin to combination antibiotic treatment outweighs the potential risk.

Currently there are 2 antitoxins in the CDC Strategic National Stockpile: raxibacumab and Anthrax Immune Globulin Intravenous (AIGIV). Both antitoxins inhibit binding of Protective Antigen (PA) to anthrax toxin receptors and translocation of the 2 primary toxins (Lethal Toxin (LT) and Edema Toxin (ET)) into cells.^[1]

Raxibacumab

Raxibacumab is a recombinant, fully humanized, IgG1λ monoclonal antibody. It appeared safe and well tolerated in 333 healthy adults who received the recommended dose of 40 mg/kg.

Most adverse events were transient and mild to moderate in severity. Pruritis was noted in 2.1% of persons treated with raxibacumab and in none treated with placebo. Although raxibacumab has not been given to patients with systemic anthrax, it is FDA-approved for postexposure prophylaxis.^[1]

Anthrax Immune Globulin

AIGIV is a human polyclonal antiserum made from plasma of persons immunized with Anthrax Vaccine Absorbed (AVA), which might have some direct effect on Lethal Factor (LF) and Edema Factor (EF). It was evaluated in 74 healthy adult volunteers and appears safe and well tolerated at all doses tested.

The most frequently reported adverse events were headache pharyngolaryngeal pain, and nausea.

AIGIV is not FDA approved and could be made available under an Investigational New Drug protocol or an Emergency Use Authorization during a declared emergency.^[1]

Hospitalization

Many patients with cutaneous anthrax can be treated as outpatients.

Patients with symptoms or signs of systemic involvement (e.g., tachycardia, tachypnea, hypotension, hyperthermia, hypothermia, leukocytosis) or with lesions that involve the head, neck, or upper torso or that are large, bullous, multiple, or surrounded by edema, have higher mortality rates. Hospitalization is warranted for all patients with systemic cutaneous anthrax; gastrointestinal, injection, or inhalation anthrax; or anthrax meningitis or bacteremia.

Supportive Treatment

Failure to fulfill systemic inflammatory response syndrome criteria should not decrease concern for sepsis because patients with systemic anthrax might not initially appear critically ill. Inhalation anthrax can have a prodromal phase followed by a fulminant phase. Patients with systemic anthrax have had debilitating symptoms, followed first by transitory improvement and then by precipitous hemodynamic deterioration. Because of this potential for sudden decompensation, hospitalized patients should have careful hemodynamic monitoring, including continuous pulse oximetry and telemetry.

Hemodynamic Support

Standard sepsis and septic shock guidelines should be followed for anthrax patients. Common complications of anthrax infections including microangiopathic hemolytic anemia, coagulopathy, thrombocytopenia, and hemorrhage must be aggressively managed, since they might pose contraindications to invasive central catheter placement.^[5]

Fresh frozen plasma and plasmapheresis should be considered, and fibrinogen levels should be kept >100 mg/dL.

An echocardiogram might be needed to identify pericardial effusions.^[6]

Mechanical Ventilation

In addition to the need for mechanical ventilation for respiratory distress or airway protection for persons with altered mental status, some patients with anthrax might require respiratory support for airway edema. Substantial edema with fatal outcome can occur with cutaneous lesions involving the head, neck, or thorax, and with oropharyngeal lesions.^[7]

In inhalation anthrax, although respiratory failure is more consistent with reaccumulating pleural effusions than with adult respiratory distress syndrome, standard mechanical ventilator principles apply.^[8] The need for ventilation in some patients and the duration of ventilation in others may be reduced by pleural space drainage.

Adjunctive Corticosteroids

There are limited data on steroid use for documented anthrax meningitis, however, adjunctive intravenous dexamethasone is the standard of care for patients with suspected bacterial meningitis and should be started at the time of initial antibiotic therapy to prevent neurologic sequelae.^[9]

Adjunctive corticosteroids should be considered in patients who had a history of use of:^[10]^[11]

Endocrine therapy
Corticosteroid therapy
Edema, especially of the head or neck
Evidence of anthrax meningitis
Vasopressor-resistant shock

Interventions

Procedures

Drainage of pleural fluid and ascites is believed to improve survival by reducing the toxin level and by decreasing mechanical lung compression. These data support the need for early and aggressive drainage of any clinically or radiographically apparent pleural effusions; chest tube drainage is recommended over thoracentesis because many effusions will require prolonged drainage. ^[1]

Thoracotomy or video-assisted thoracic surgery might be required to remove gelatinous or loculated collections. Ascites should also be drained and monitored for reaccumulation.^[1]

Surgery

Surgery for cutaneous anthrax can lead to dissemination and poor outcome. Surgery is contraindicated for acute disease, with the exception of tracheotomy for airway obstruction and surgical intervention for large or circumferential extremity lesions causing compartment syndrome.

Surgery may be indicated for gastrointestinal anthrax to identify and address potentially fatal complications, such as bowel ischemia, necrosis, and perforation.^[12]

For injection anthrax, surgery is used to obtain diagnostic specimens to differentiate the infection from necrotizing fasciitis and to remove the necrotic nidus of infection, which may be a toxin and spore reservoir. Surgery for injection anthrax should be more limited than that for necrotizing fasciitis, and resection should be performed only to healthy tissue. Compression of soft tissues can be released by incision, excision, or fasciotomy and might be required for treatment of compartment syndrome.^[13]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".
↑ ^2.0 ^2.1 ^2.2 Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT; et al. (2014). "Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults". Emerg Infect Dis. 20 (2). doi:10.3201/eid2002.130687. PMC 3901462. PMID 24447897.
↑ Meaney-Delman D, Zotti ME, Creanga AA, Misegades LK, Wako E, Treadwell TA; et al. (2014). "Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women". Emerg Infect Dis. 20 (2). doi:10.3201/eid2002.130611. PMC 3901460. PMID 24457117.
↑ ^4.0 ^4.1 Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D; et al. (2014). "Pediatric anthrax clinical management". Pediatrics. 133 (5): e1411–36. doi:10.1542/peds.2014-0563. PMID 24777226.
↑ Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012". Intensive Care Med. 39 (2): 165–228. doi:10.1007/s00134-012-2769-8. PMID 23361625.
↑ Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M; et al. (2001). "Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States". Emerg Infect Dis. 7 (6): 933–44. doi:10.3201/eid0706.010604. PMC 2631903. PMID 11747719.
↑ Peck RN, Fitzgerald DW (2007). "Cutaneous anthrax in the Artibonite Valley of Haiti: 1992-2002". Am J Trop Med Hyg. 77 (5): 806–11. PMID 17984330.
↑ Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L; et al. (1998). "The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome". Am J Respir Crit Care Med. 157 (4 Pt 1): 1332–47. doi:10.1164/ajrccm.157.4.ats2-98. PMID 9563759.
↑ de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators (2002). "Dexamethasone in adults with bacterial meningitis". N Engl J Med. 347 (20): 1549–56. doi:10.1056/NEJMoa021334. PMID 12432041. Review in: ACP J Club. 2003 May-Jun;138(3):60
↑ Sejvar JJ, Tenover FC, Stephens DS (2005). "Management of anthrax meningitis". Lancet Infect Dis. 5 (5): 287–95. doi:10.1016/S1473-3099(05)70113-4. PMID 15854884.
↑ Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R; et al. (2009). "Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review". JAMA. 301 (22): 2362–75. doi:10.1001/jama.2009.815. PMID 19509383.
↑ Binkley CE, Cinti S, Simeone DM, Colletti LM (2002). "Bacillus anthracis as an agent of bioterrorism: a review emphasizing surgical treatment". Ann Surg. 236 (1): 9–16. PMC 1422543. PMID 12131080.
↑ Knox D, Murray G, Millar M, Hamilton D, Connor M, Ferdinand RD; et al. (2011). "Subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis". J Bone Joint Surg Br. 93 (3): 414–7. doi:10.1302/0301-620X.93B3.25976. PMID 21357967.

Template:WikiDoc Sources

[CDC-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 "Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults".

[pmid24447897-2] 2.0 ^2.1 ^2.2 Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT; et al. (2014). "Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults". Emerg Infect Dis. 20 (2). doi:10.3201/eid2002.130687. PMC 3901462. PMID 24447897.

[pmid24457117-3] Meaney-Delman D, Zotti ME, Creanga AA, Misegades LK, Wako E, Treadwell TA; et al. (2014). "Special considerations for prophylaxis for and treatment of anthrax in pregnant and postpartum women". Emerg Infect Dis. 20 (2). doi:10.3201/eid2002.130611. PMC 3901460. PMID 24457117.

[pmid24777226-4] 4.0 ^4.1 Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D; et al. (2014). "Pediatric anthrax clinical management". Pediatrics. 133 (5): e1411–36. doi:10.1542/peds.2014-0563. PMID 24777226.

[pmid23361625-5] Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM; et al. (2013). "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012". Intensive Care Med. 39 (2): 165–228. doi:10.1007/s00134-012-2769-8. PMID 23361625.

[pmid11747719-6] Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M; et al. (2001). "Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States". Emerg Infect Dis. 7 (6): 933–44. doi:10.3201/eid0706.010604. PMC 2631903. PMID 11747719.

[pmid17984330-7] Peck RN, Fitzgerald DW (2007). "Cutaneous anthrax in the Artibonite Valley of Haiti: 1992-2002". Am J Trop Med Hyg. 77 (5): 806–11. PMID 17984330.

[pmid9563759-8] Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L; et al. (1998). "The American-European Consensus Conference on ARDS, part 2: Ventilatory, pharmacologic, supportive therapy, study design strategies, and issues related to recovery and remodeling. Acute respiratory distress syndrome". Am J Respir Crit Care Med. 157 (4 Pt 1): 1332–47. doi:10.1164/ajrccm.157.4.ats2-98. PMID 9563759.

[pmid12432041-9] Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators (2002). "Dexamethasone in adults with bacterial meningitis". N Engl J Med. 347 (20): 1549–56. doi:10.1056/NEJMoa021334. PMID 12432041. Review in: ACP J Club. 2003 May-Jun;138(3):60

[pmid15854884-10] Sejvar JJ, Tenover FC, Stephens DS (2005). "Management of anthrax meningitis". Lancet Infect Dis. 5 (5): 287–95. doi:10.1016/S1473-3099(05)70113-4. PMID 15854884.

[pmid19509383-11] Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R; et al. (2009). "Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review". JAMA. 301 (22): 2362–75. doi:10.1001/jama.2009.815. PMID 19509383.

[pmid12131080-12] Binkley CE, Cinti S, Simeone DM, Colletti LM (2002). "Bacillus anthracis as an agent of bioterrorism: a review emphasizing surgical treatment". Ann Surg. 236 (1): 9–16. PMC 1422543. PMID 12131080.

[pmid21357967-13] Knox D, Murray G, Millar M, Hamilton D, Connor M, Ferdinand RD; et al. (2011). "Subcutaneous anthrax in three intravenous drug users: a new clinical diagnosis". J Bone Joint Surg Br. 93 (3): 414–7. doi:10.1302/0301-620X.93B3.25976. PMID 21357967.

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 :::::::*  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
 ::::::* 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 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
 ::::::::* 3.2.5.1.2.1.2 '''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
 ::::::* 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 week
-:::::::::* 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 weeks 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 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 20 mg/kg/day IV divided q12h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 ::::::::* '''For 1–4 week of age'''
 :::::::::* Preferred regimen (1): [[Clindamycin]] 15 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 :::::::* 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 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 ::::::::* '''For 1–4 week of age'''
 :::::::::* Preferred regimen (1): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 :::::::* 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 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Doxycycline]] 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 weeks
 :::::::::* Preferred regimen (4): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 ::::::::* For 1–4 week of age :
 :::::::::* Preferred regimen (1): [[Clindamycin]] 20 mg/kg/day IV divided q6h for 2–3 weeks
 :::::::::* Preferred regimen (2): [[Linezolid]] 30 mg/kg/day IV divided q8h for 2–3 weeks
 :::::::::* Preferred regimen (3): [[Doxycycline]] 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 weeks
 :::::::::* Preferred regimen (4): [[Rifampin]] 10 mg/kg/day IV q24h for 2–3 weeks
 :::::::::* Note: Duration of therapy for 2–3 weeks, 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
@@ Line 706: / Line 497: @@
 :::::::::* 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'''
+:::::::* 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
-:::::::::* 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.
@@ Line 803: / Line 558: @@
 :::* 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
@@ Line 823: / Line 571: @@
 :::* 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'''
+:::::* 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