Comparison of gatifloxacin, moxifloxacin and ciprofloxacin for treatment of experimental Burkholderia pseudomallei infection.
OBJECTIVE
To compare the efficacy of moxifloxacin, gatifloxacin and ciprofloxacin for the post-exposure prophylaxis and treatment of experimental Burkholderia pseudomallei infection. The presence of persistent infection in treated animals and the rate of relapse following dexamethasone treatment were also investigated.


METHODS
BALB/c mice were inoculated subcutaneously with 1.75 x 10(6) cfu of B. pseudomallei strain 576. Gatifloxacin, moxifloxacin and ciprofloxacin (100 mg/kg) were given orally at 12 hourly intervals for 14 days starting at 6 h, 7 days or 12 days post-challenge. Control mice did not receive antibiotic therapy.


RESULTS
No regimen gave 100% protection. Prophylaxis was most effective when started 6 h post-challenge, with survival rates at 42 days for ciprofloxacin, gatifloxacin and moxifloxacin being 58%, 75% and 75%, respectively. For treatment started at day 7 post-challenge, survival rates were 17%, 11% and 44%, respectively. When antibiotic treatment was delayed until day 12 post-challenge, survival rates fell to 21%, 17% and 28%, respectively. Following dexamethasone treatment of survivors at 42 days post-challenge, relapses occurred in all treatment groups.


CONCLUSIONS
Fluoroquinolones do not provide good post-exposure protection against infection with B. pseudomallei. The newer agents moxifloxacin and gatifloxacin are not significantly better than ciprofloxacin for this purpose.
Steward
J
J
Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK. jasteward@dstl.gov.uk
Piercy
T
T
Lever
M S
MS
Nelson
M
M
Simpson
A J H
AJ
Brooks
T J G
TJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D003907:Dexamethasone / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D000077734:Gatifloxacin; D005938:Glucocorticoids / Q000494:pharmacology; D008554:Melioidosis / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D011804:Quinolines / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D005938:Glucocorticoids; D011804:Quinolines; D002939:Ciprofloxacin; D003907:Dexamethasone; D000077734:Gatifloxacin; D000077266:Moxifloxacin