APPENDIX 4

Triple Therapy for Systemic Anthrax (Anthrax Meningitis or Disseminated Infection and Meningitis Cannot Be Ruled Out) for Children 1 Month of Age and Older

1. A bactericidal antimicrobial (fluoroquinolone)
Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided every 8 h (not to exceed 400 mg/dose)a
OR
Levofloxacin <50 kg: 16 mg/kg/day, IV, divided every 12 h (not to exceed 250 mg/dose); >50 kg: 500 mg, IV, every 24 h
OR
Moxifloxacin 3 mo to <2 y: 12 mg/kg/day, IV, divided every 12 h (not to exceed 200 mg/dose)
2–5 y: 10 mg/kg/day, IV, divided every 12 h (not to exceed 200 mg/dose)
6–11 y: 8 mg/kg/day, IV, divided every 12 h (not to exceed 200 mg/dose)
12–17 y, ≥45 kg body weight: 400 mg, IV, once daily
12–17 y, <45 kg body weight: 8 mg/kg/day, IV, divided every 12 h (not to exceed 200 mg/dose)
PLUS
2. A bactericidal antimicrobial (β-lactam or glycopeptide)
a. For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown
Meropenem, 120 mg/kg/day, IV, divided every 8 h (not to exceed 2 g/dose)
OR
Imipenem/cilastatin,b 100 mg/kg/day, IV, divided every 6 h (not to exceed 1 g/dose)
OR
Doripenem,c 120 mg/kg/day, IV, divided every 8 h (not to exceed 1 g/dose)
OR
Vancomycin, 60 mg/kg/day, IV, divided every 8 h
b. Alternatives for penicillin-susceptible strains
Penicillin G, 400 000 U/kg/day, IV, divided every 4 h (not to exceed 4 MU/dose)
OR
Ampicillin, 400 mg/kg/day, IV, divided every 6 h (not to exceed 3 g/dose)
PLUS
3. A Protein Synthesis Inhibitor
Linezolidd: <12 y old: 30 mg/kg/day, IV, divided every 8 h≥12 y old: 30 mg/kg/day, IV, divided every 12 h (not to exceed 600 mg/dose)
OR
Clindamycin, 40 mg/kg/day, IV, divided every 8 h (not to exceed 900 mg/dose)
OR
Rifampin,e 20 mg/kg/day, IV, divided every 12 h (not to exceed 300 mg/dose)
OR
Chloramphenicol,f 100 mg/kg/day, IV, divided every 6 h
Duration of therapy: for 2–3 wk or greater, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness (see Appendix 1).
  • Systemic anthrax includes anthrax meningitis; inhalation anthrax; or injection, gastrointestinal, and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck.

  • Children with altered mental status, signs of meningeal inflammation, or focal neurologic deficits should be considered to have CNS infection if CSF examination is not possible. Normal CSF may not completely exclude deep brain hemorrhage/abscess.

  • Bold font: preferred antimicrobial agent.

  • Normal font: alternative selections are listed in order of preference for therapy for patients who cannot tolerate first-line therapy or if first-line therapy is unavailable.

  • Doses are provided for children with normal renal and hepatic function. Doses may vary for those with some degree of organ failure.

  • a A 400-mg dose of ciprofloxacin, IV, provides an equivalent exposure to that of a 500-mg ciprofloxacin oral tablet.

  • b Increased risk of seizures associated with imipenem/cilastatin therapy.

  • c Doripenem is approved in Japan at this dose for the treatment of community-acquired bacterial meningitis.

  • d Linezolid should be used with caution in patients with thrombocytopenia, as it may exacerbate it. Linezolid use for >14 days carries additional hematopoietic toxicity.

  • e Rifampin is not a protein synthesis inhibitor; it may also be used in combination therapy based on in vitro synergy for some strains of staphylococci. Not evaluated for B anthracis.

  • f Should be used only if other options are not available, because of toxicity concerns.