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J Antimicrob Chemother. 2008 Mar;61(3):674-8. doi: 10.1093/jac/dkm527. Epub 2008 Jan 12.

Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole.

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  • 1Defence Medical and Environmental Research Institute, DSO, National Laboratories, 27 Medical Drive, 117510 Singapore, Singapore. ssuppiah@dso.org.sg

Abstract

OBJECTIVES:

Melioidosis, a potentially fatal disease of humans and animals, is caused by the gram-negative bacterium, Burkholderia pseudomallei. There is no approved vaccine or effective prophylaxis. Given its potential as a bioterrorism agent and a cause of serious laboratory-acquired infection, we studied the efficacy of pre- and post-exposure oral antibiotic prophylaxis in BALB/c mice infected with aerosolized B. pseudomallei through the inhalational route.

METHODS:

Amoxicillin/clavulanic acid, doxycycline or co-trimoxazole was administered 48 h before infection as pre-exposure prophylaxis, orally, twice daily and continued up to 10 days post-challenge. In the post-exposure prophylaxis regimen, the oral antibiotics were administered twice daily, at 0, 10, 24 and 48 h and continued for 10 days. Survival of all animals was observed until 21 days.

RESULTS:

All infected control animals developed infection between 24 and 48 h, and died within 5 days. Animals receiving amoxicillin/clavulanic acid as pre-exposure prophylaxis succumbed to the disease at day 7, whereas those in the co-trimoxazole and doxycycline groups had survival rate of 100% and 80%, respectively, at day 21. As post-exposure prophylaxis, all antibiotics were not effective when treatment was initiated 48 h post-challenge. However, animals receiving co-trimoxazole had a 100% survival rate when the antibiotic was started 0, 10 and 24 h post-infection, and amoxicillin/clavulanic acid was the least effective.

CONCLUSIONS:

Co-trimoxazole appears to be an effective oral antibiotic both as pre- and post-exposure prophylaxis to B. pseudomallei. Data derived from this study have important implications on the management of laboratory accidents or following an intentional release of B. pseudomallei, a potential bioterrorism agent.

PMID:
18192684
[PubMed - indexed for MEDLINE]
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