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Could the Duration of Postexposure Antibiotic Prophylaxis Against Inhalational Anthrax be Shortened?

By Luciana Borio, M.D. and John G. Bartlett, M.D., March 17, 2006

The CDC recommends 60 days of postexposure antibiotic prophylaxis in unvaccinated persons after exposure to anthrax spores [1]. This long duration of antibiotic prophylaxis is deemed necessary because spores may persist for a protracted period of time before germinating. If antibiotics are discontinued prematurely in an unvaccinated person, residual spores may germinate and cause disease. However, the experience in 2001 suggested that adherence to 60 days of antibiotics is poor [2].

In 2002, the ACIP recommended the inclusion of anthrax vaccine given at 0, 2, and 4 weeks in combination with antibiotic prophylaxis [1]. This must be administered under an Investigational New Drug (IND) application since anthrax vaccine is not licensed for postexposure use, and the package insert of the licensed vaccine calls for the administration of 6 doses given over 18 months. When combined with vaccine, antibiotics should be continued for 7 to 14 days after the third vaccine dose [1]. Antibody titers in vaccinated persons peak at 14 days after the third dose [3].

In order to investigate whether a short course of antibiotic prophylaxis could prevent disease if combined with anthrax vaccine, Nicholas Vietri and colleagues from the USAMRIID and the NIAID exposed 24 Rhesus macaques to approximately 1600 LD50 of spores by aerosol [4]. Ten macaques were treated with oral ciprofloxacin, beginning 1 to 2 hours after exposure, for 14 days. Ten macaques were treated with ciprofloxacin and also received three doses of anthrax vaccine (AVA) at days 0, 14, and 28. Four macaques did not receive antibiotics or vaccine.

Table: Results

Survived

Died

Cipro (n=9)*

4

5

Cipro + AVA (n=10)

10

0

Control (n=4)

0

4

 *One animal died of aspiration pneumonia and was excluded from the analysis.

All animals that received antibiotic and vaccine survived the challenge, whereas only 4 of 9 (44%) that received antibiotics alone survived. All of the animals in the control group died within 5 days of challenge, and those in the antibiotic only group died within 10 days of stopping antibiotics.

These results suggest that the addition of postexposure vaccination can shorten the duration of antimicrobial prophylaxis after exposure to anthrax spores. Since all of the animals that died in the antibiotic only group did so within 10 days of stopping antibiotics, one may also conclude that two doses of AVA administered at 0 and 14 days in combination with the antibiotics were sufficient to protect the animals in the antibiotic plus vaccine group. The results of this study suggest an approach to postexposure prophylaxis that could facilitate the public health response to a bioterrorism event involving anthrax, while also sparing significant amounts of antibiotics and anthrax vaccine.

References

  1. Centers for Disease Control and Prevention. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2002;51:1024-6. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5145a4.htm . Accessed 3-15-06.

  2. Shepard CW, Soriano-Gabarro-Soriano M, Zell ER, et al. Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence. Emerg Infect Dis 2002;8:1124-32. http://www.cdc.gov/ncidod/EID/vol8no10/02-0349.htm . Accessed 3-15-06.

  3. Pittman PR, Kim-Ahn G, Pifat DY, et al. Anthrax vaccine: immunogenicity and safety of a dose- reduction, route-change comparison study in humans. Vaccine 2002;20:1412-20.

  4. Vietri NK, Purcell BK, Lawler JV, et al. Short course postexposure antibiotic prophylaxis when combined with vaccination protects against inhalational anthrax. Abstract LB-23, 43rd Annual Meeting of IDSA, San Francisco, October 6-9, 2005