Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole.
OBJECTIVE
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.
Sivalingam
Suppiah Paramalingam
SP
Defence Medical and Environmental Research Institute, DSO, National Laboratories, 27 Medical Drive, 117510 Singapore, Singapore. ssuppiah@dso.org.sg
Sim
Siew Hoon
SH
Jasper
Liaw Chin Wen
LC
Wang
Dongling
D
Liu
Yichun
Y
Ooi
Eng Eong
EE
D000658:Amoxicillin / Q000008:administration & dosage*; D000818:Animals; D019072:Antibiotic Prophylaxis / Q000379:methods; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000502:physiology; D019818:Clavulanic Acid / Q000008:administration & dosage*; D004318:Doxycycline / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D008554:Melioidosis / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*
D019818:Clavulanic Acid; D000658:Amoxicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004318:Doxycycline