Rationale:

• Postexposure antibiotic prophylaxis prevents inhalational anthrax.
• Ciprofloxacin, doxycycline, and levofloxacin have been approved by the FDA and are recommended by the CDC for postexposure prophylaxis for anthrax.
• Ciprofloxacin and doxycycline are considered to be equivalent first-line antimicrobial agents for postexposure prophylaxis. Levofloxacin is recommended as a second-line postexposure antimicrobial agent.
• Postexposure ciprofloxacin and doxycycline appear to be protective in humans.
• β-Lactam resistance has been reported in naturally occurring B. anthracis isolates.
• Antibiotic resistance in B. anthracis can be readily induced in vitro to a variety of antimicrobial agents.
• B. anthracis spores, which are dormant and do not cause active infection, can germinate weeks to months after exposure and cause inhalational anthrax.
• Vaccination against anthrax may prevent disease from the remaining spores once antibiotic prophylaxis is discontinued.
• Anthrax vaccine is safe, but side effects occur.

Evidence:

• Rhesus monkeys exposed to inhaled anthrax (approximately 8 LD₅₀) and then given postexposure penicillin, doxycycline, or ciprofloxacin for 30 days were protected while on antibiotic therapy. However, after discontinuation of antibiotics, deaths occurred up to 58 days after aerosol exposure. This study also showed that complete long-term survival after discontinuation of antibiotics occurred when postexposure antibiotic treatment was combined with anthrax vaccination (14).
• Rhesus monkeys exposed to large doses of inhaled anthrax spores and then given postexposure prophylaxis with ciprofloxacin for 14 days experienced a high mortality rate after antibiotics were discontinued. Adding AVA to postexposure antibiotic prophylaxis resulted in a statically significant increase in survival (15).
• B. anthracis strains resistant to penicillin and tetracycline have been engineered (16).
• Anthrax spores were noted in the lung parenchyma of experimentally infected rhesus monkeys for up to 100 days (17).
• The last case of inhalational anthrax during the 1979 Sverdlovsk outbreak was 43 days after exposure (18).
• Animal and human studies support the efficacy of anthrax vaccine for prevention of inhalational and cutaneous anthrax (1; 2; 3; 4).
• Mild cutaneous reactions occur in 20% of patients vaccinated, whereas severe local reactions and systemic reactions occur in 1% (1; 8; 9).
• Data collected during a postexposure antibiotic prophylaxis campaign showed that adherence to a full 60-day course of antibiotic therapy was only approximately 44%. Poor adherence was not necessarily related to adverse events (19).
• A cost-effectiveness analysis showed that postexposure antibiotic therapy combined with vaccination would be the most effective and least costly strategy for prophylaxis and treatment of patients in the event of a bioterror attack with anthrax (20).

Comments:

• Anthrax vaccine for postexposure prophylaxis can be obtained from the CDC under an investigational new drug protocol for isolated cases or under an emergency use authorization for outbreaks.