Comparison of efficacy of ciprofloxacin and doxycycline against experimental melioidosis and glanders

Melioidosis and glanders are caused by the closely related species Burkhold eria pseudomallei and Burkholderia mallei, respectively. Whereas melioidosi s is a significant cause of morbidity in south-east Asia, glanders is extre mely rare. The efficacies of ciprofloxacin and doxycycline were assessed ag ainst a strain of B. pseudomallei and a strain of B. mallei which were susc eptible to both antimicrobials in vitro. Porton outbred mice and Syrian ham sters were given 40 mg/kg of either doxycycline or ciprofloxacin twice dail y by sc injection according to one of three regimens: dosing starting 48 h before challenge and continuing for 5 days post-challenge; 5 days' therapy starting immediately after challenge; 5 days' therapy starting 24 h after c hallenge. Mice were challenged ip with B. pseudomallei 4845 and hamsters we re challenged ip with B. mallei 23344. Antimicrobial efficacy was determine d by the shift in the median lethal dose (MLD). Ciprofloxacin prophylaxis a nd immediate therapy both raised the MLD of B. pseudomallei to 4 x 10(6) cf u from 19 cfu in untreated animals, but therapeutic ciprofloxacin only rais ed the MLD to 180 cfu. The results for doxycycline were similar. Ciprofloxa cin prophylaxis raised the MLD of B. mallei 23344 to 4.6 x 10(5) cfu compar ed with 4 cfu in untreated controls. Immediate therapy raised the MLD to 7. 0 x 10(4) cfu and therapy raised the MLD to 1.6 x 10(3) cfu. All regimens o f doxycycline protected hamsters against challenges of up to 2 x 10(7) cfu. Despite using a susceptible strain of B. pseudomallei, neither antimicrobi al was effective when used therapeutically. The timely administration of ei ther antimicrobial, however, was effective in preventing symptomatic infect ion. Doxycycline was the superior of the two antimicrobials against experim ental glanders although relapse did occur in treated animals approximately 4-5 weeks after challenge.