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Efficacy of Gentamicin and Doxycycline in the Treatment of Plague

By Eric Toner, M.D.  December 13, 2006

In an article published in the March 1, 2006 issue of Clinical Infectious Diseases [1], Dr. William Mwengee and colleagues report on a prospective, open-label, randomized clinical trial comparing gentamicin and doxycycline for the treatment of naturally-occurring plague in Tanzania. This is the first randomized, controlled study of gentamicin’s efficacy in treating plague.

Five antibiotics are currently licensed by the FDA with an indication for the treatment of plague, namely, streptomycin and four members of the tetracycline family: tetracycline, doxycycline, demeclocycline and minocycline. However, streptomycin is no longer widely available in the U.S. and many other countries, leaving the tetracyclines as the only FDA approved therapies and two of them, tetracycline and demeclocycline, are no longer widely used. As a result, gentamicin, which is widely available, has often been used in place of streptomycin [2], but had never been studied in a controlled fashion as a treatment for plague. Mwengee’s study compared the efficacy of gentamicin monotherapy with standard doxycycline therapy.

The trial involved 65 adults and children with bubonic, septicemic, or pneumonic plague. Patients received either gentamicin 2.5 mg/kg IM q12h for 7 days or doxycycline 100mg (2.2 mg/kg for children) po q12h for 7 days. Both drugs were highly effective and produced similar results: 94% of patients treated with gentamicin and 97% of patients treated with doxycycline had a favorable response (cure or improved condition). There were no relapses. This high response rate is attributed to the prompt initiation of therapy after onset of illness, which averaged 1 day. It should also be noted that the majority of the enrolled patients (~80 %) had bubonic plague rather than the more severe septicemic or pneumonic forms of the disease that carry higher case fatality rates. 

The study confirms that parenteral gentamicin is an effective alternative to streptomycin in the treatment of plague. Yersinia pestis, the causative agent of plague, is classified as a category A bioterrorism agent because of its potential to be delivered as an aerosol and cause severe, rapid illness in large numbers of victims. With an estimated incubation period of 2 to 4 days after aerosol exposure and a rapid progression to death without prompt and appropriate treatment [3], a successful medical response requires ready availability of a large quantity of an effective antibiotic. Fortunately, both gentimicin and doxycycline are among the most commonly used antibiotics and have been stockpiled by the federal government to be used in the event of an emergency. 

References

  1. Mwengee W, Butler T, Mgema S, et al. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis 2006;42:614-21. Available online at http://www.journals.uchicago.edu/cgi-bin/resolve?id=doi:10.1086/500137. Accessed 12/11/06.

  2. Centers for Disease Control and Prevention. Human plague--four states, 2006. MMWR Morb Mortal Wkly Rep 2006;55:940-3. Available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm55d825a1.htm?s_cid=mm55d825a1_e. Accessed 12/13/06

  3. Inglesby T, Dennis D, Henderson, D et al. Plague as a biological weapon: medical and public health management.  JAMA 2000;283:2281-2290. Available online at http://jama.ama-assn.org/cgi/content/full/283/17/2281. Accessed 12/11/06.