Rationale:

• Antibiotic-resistant B. anthracis has been engineered in the laboratory.
• Combination therapy is a reasonable therapeutic approach in life-threatening disease with anthrax.
• Rifampin, vancomycin, penicillin or ampicillin, and meropenem have been recommended by experts from a CDC-sponsored conference on anthrax clinical guidelines.
• Clindamycin can inhibit protein synthesis, which may reduce anthrax toxin production.
• Treatment for 60 days is justified because of the risk of possible disease from delayed germination of inhaled B. anthracis spores.
• Early treatment improves the chances of survival.
• The high death rate from anthrax infection outweighs the risk antimicrobial agents pose to pregnant women and children.
• Although antibiotics are the mainstay of treatment, neutralization of anthrax toxin in the bloodstream by antiserum may, theoretically, provide additional benefit to patients with severe systemic anthrax.

Evidence:

• Following the 2001 anthrax attacks, patients with inhalational anthrax had a greater chance of survival if they were treated with two or more iv antibiotics (28).
• Ciprofloxacin is preferred over doxycycline, unless there is a major contraindication to ciprofloxacin, because ciprofloxacin penetrates the CNS better than doxycycline and is a bactericidal agent (51).
• An animal study shows theoretically that clindamycin may decrease toxin production by B. anthracis (52).
• B. anthracis resistant to penicillin, tetracycline, and ofloxacin have been engineered in the laboratory (16; 53).
• Close monitoring of patients being treated for anthrax is mandatory because antibiotic resistance can be generated in vitro (54).
• Human-derived anthrax immune globulin was part of a successful treatment regimen in a case of inhalational anthrax in 2006 (55).
• Animals with inhalational anthrax treated with raxibacumab, a human monoclonal antibody directed against a component of the anthrax toxin, showed increased survival compared to animals treated with placebo (56).

Comments:

• When the patient is stable, iv antibiotics can be switched to oral antibiotics to finish the course of therapy. Ciprofloxacin is an excellent choice as an oral agent because its bioavailability is 70% to 80%.