title: Comparison of efficacy of ciprofloxacin and doxycycline against experimental melioidosis and glanders.
abstract: Melioidosis and glanders are caused by the closely related species Burkholderia pseudomallei and Burkholderia mallei, respectively. Whereas melioidosis is a significant cause of morbidity in south-east Asia, glanders is extremely rare. The efficacies of ciprofloxacin and doxycycline were assessed against a strain of B. pseudomallei and a strain of B. mallei which were susceptible to both antimicrobials in vitro. Porton outbred mice and Syrian hamsters were given 40 mg/kg of either doxycycline or ciprofloxacin twice daily by sc injection according to one of three regimens: dosing starting 48 h before challenge and continuing for 5 days postchallenge; 5 days' therapy starting immediately after challenge; 5 days' therapy starting 24 h after challenge. Mice were challenged ip with B. pseudomallei 4845 and hamsters were challenged ip with B. mallei 23344. Antimicrobial efficacy was determined by the shift in the median lethal dose (MLD). Ciprofloxacin prophylaxis and immediate therapy both raised the MLD of B. pseudomallei to 4 x 10(6) cfu from 19 cfu in untreated animals, but therapeutic ciprofloxacin only raised the MLD to 180 cfu. The results for doxycycline were similar. Ciprofloxacin prophylaxis raised the MLD of B. mallei 23344 to 4.6 x 10(5) cfu compared 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 of doxycycline protected hamsters against challenges of up to 2 x 10(7) cfu. Despite using a susceptible strain of B. pseudomallei, neither antimicrobial was effective when used therapeutically. The timely administration of either antimicrobial, however, was effective in preventing symptomatic infection. Doxycycline was the superior of the two antimicrobials against experimental glanders although relapse did occur in treated animals approximately 4-5 weeks after challenge.
authors.affiliation: CBD Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. drprussell@hotmail.com
authors.forename: P
authors.initials: P
authors.lastname: Russell
authors.forename: S M
authors.initials: SM
authors.lastname: Eley
authors.forename: J
authors.initials: J
authors.lastname: Ellis
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: D L
authors.initials: DL
authors.lastname: Bell
authors.forename: D J
authors.initials: DJ
authors.lastname: Kenny
authors.forename: R W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D019121:Burkholderia Infections / Q000188:drug therapy / Q000382:microbiology; D016957:Burkholderia pseudomallei / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D002939:Ciprofloxacin / Q000627:therapeutic use*; D006224:Cricetinae; D004318:Doxycycline / Q000627:therapeutic use*; D005260:Female; D005896:Glanders / Q000188:drug therapy* / Q000382:microbiology; D008554:Melioidosis / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D004318:Doxycycline