In vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice

J Antimicrob Chemother. 2005 Dec;56(6):1069-73. doi: 10.1093/jac/dki359. Epub 2005 Oct 13.

Abstract

Objectives: 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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Aza Compounds / administration & dosage
  • Aza Compounds / pharmacology
  • Aza Compounds / therapeutic use*
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacology
  • Ciprofloxacin / therapeutic use*
  • Colony Count, Microbial
  • Dexamethasone / administration & dosage
  • Disease Models, Animal
  • Female
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / pharmacology
  • Fluoroquinolones / therapeutic use*
  • Francisella tularensis / drug effects*
  • Gatifloxacin
  • Mice
  • Mice, Inbred BALB C
  • Moxifloxacin
  • Quinolines / administration & dosage
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Survival Analysis
  • Tularemia / drug therapy*
  • Tularemia / mortality
  • Tularemia / pathology

Substances

  • Anti-Bacterial Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Ciprofloxacin
  • Dexamethasone
  • Gatifloxacin
  • Moxifloxacin