Efficacy of post exposure administration of doxycycline in a murine model of inhalational melioidosis.
Burkholderia pseudomallei is the causative agent of melioidosis. Treatment of melioidosis is suboptimal and developing improved melioidosis therapies requires animal models. In this report, we exposed male BALB/c mice to various amounts of aerosolized B. pseudomallei 1026b to determine lethality. After establishing a median lethal dose (LD(50)) of 2,772 colony forming units (cfu)/animal, we tested the ability of doxycycline administered 6 hours after exposure to a uniformly lethal dose of ~20 LD(50) to prevent death and eliminate bacteria from the lung and spleens. Tissue bacterial burdens were examined by PCR analysis. We found that 100% of mice treated with doxycycline survived and B. pseudomallei DNA was not amplified from the lungs or spleens of most surviving mice. We conclude the BALB/c mouse is a useful model of melioidosis. Furthermore, the data generated in this mouse model indicate that doxycycline is likely to be effective in post-exposure prophylaxis of melioidosis.
Battelle, Battelle Memorial Institute, Columbus, OH, USA. gelhaush@battelle.org
H Carl
HC
Gelhaus
Michael S
MS
Anderson
David A
DA
Fisher
Michael T
MT
Flavin
Ze-Qi
ZQ
Xu
Daniel C
DC
Sanford
D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000008:administration & dosage*; D007928:Lethal Dose 50; D008297:Male; D008554:Melioidosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D051379:Mice
D000336:Aerosols; D000900:Anti-Bacterial Agents; D004318:Doxycycline