In vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice.
OBJECTIVE
The in vivo efficacy of ciprofloxacin, gatifloxacin and moxifloxacin were assessed in an experimental Francisella tularensis Schu S4 infection in the BALB/c mouse model.


METHODS
Mice were given 100 mg/kg of antibiotic by oral administration twice daily commencing at 6, 24 or 48 h post-exposure and continued for 14 days post-exposure. All mice were challenged subcutaneously with 1 x 10(6) cfu F. tularensis Schu S4 and observed for a period of 56 days.


RESULTS
Treatment initiated 6 h post-exposure resulted in 94, 100 and 100% survival for ciprofloxacin, gatifloxacin and moxifloxacin, respectively. When treatment was delayed until 24 h post-exposure the survival rates were ciprofloxacin 67%, gatifloxacin 96% and moxifloxacin 100%. Treatment initiated at 48 h post-exposure resulted in a significant reduction in the survival rate of the ciprofloxacin-treated mice, with 0% survival compared with 84 and 62% for gatifloxacin and moxifloxacin, respectively. Non-treated infected control mice died within 96 h post-exposure. Dexamethasone given at day 42 for 7 days to suppress the animals' immune system caused relapse in all of the treatment groups.


CONCLUSIONS
Both gatifloxacin and moxifloxacin were more effective at preventing mortality than ciprofloxacin and could be considered as alternative antibiotics in the treatment of systemic F. tularensis infection.
Piercy
T
T
Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK. tjpiercy@dstl.gov.uk
Steward
J
J
Lever
M S
MS
Brooks
T J G
TJ
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005604:Francisella tularensis / Q000187:drug effects*; D000077734:Gatifloxacin; D051379:Mice; D008807:Mice, Inbred BALB C; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D014406:Tularemia / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D003907:Dexamethasone; D000077734:Gatifloxacin; D000077266:Moxifloxacin