APPENDIX 3

Combination Therapy for Systemic Anthrax When Meningitis Can Be Ruled Out (for Children 1 Month of Age and Older)

1. A bactericidal antimicrobial
a. For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided every 8 h (not to exceed 400 mg/dose)
OR
Meropenem, 60 mg/kg/day, IV, divided every 8 h (not to exceed 2 g/dose)
OR
Levofloxacin <50 kg: 20 mg/kg/day, IV, divided every 12 h (not to exceed 250 mg/dose >50 kg: 500 mg, IV, given every 24 h
OR
Imipenem/cilastatin,a 100 mg/kg/day, IV, divided every 6 h (not to exceed 1 g/dose)
OR
Vancomycin, 60 mg/kg/day, IV, divided every 8 h (follow serum concentrations)
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, 200 mg/kg/day, IV, divided every 6 h (not to exceed 3 g/dose)
PLUS
2. A Protein Synthesis Inhibitor
Clindamycin, 40 mg/kg/day, IV, divided every 8 h (not to exceed 900 mg/dose)
OR
Linezolidb (non-CNS infection dose): <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
Doxycyclinec <45 kg: 4.4 mg/kg/day, IV, loading dose (not to exceed 200 mg); ≥45 kg: 200 mg, IV, loading dose then <45 kg: 4.4 mg/kg/day, IV, divided every 12 h (not to exceed 100 mg/dose); ≥45 kg: 100 mg, IV, given every 12 h
OR
Rifampin,d 20 mg/kg/day, IV, divided every 12 h (not to exceed 300 mg/dose)
Duration of therapy: For 14 days or longer 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 inhalation anthrax; injection, gastrointestinal, or 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. A normal CSF may not completely exclude deep brain hemorrhage/abscess. See Appendix 4 for therapy of CNS infection.

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

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

  • c A single 14-day course of doxycycline is not routinely associated with tooth staining.

  • d Rifampin is not a protein synthesis inhibitor; it may also be used in combination therapy based on in vitro synergy.