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JAC Advance Access published online on October 13, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki359
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© British Crown Copyright 2005, Dstl-published with the permission of the Controller of Her Majesty's Stationery Office.
Received May 3, 2005
Revised September 9, 2005
Accepted September 9, 2005

Original article

In vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice

T. Piercy 1*, J. Steward 1, M. S. Lever 1, and T. J. G. Brooks 2

1 Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK
2 Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK; HPA Porton Down, Salisbury SP4 OJG, UK

* To whom correspondence should be addressed.
T. Piercy, E-mail: tjpiercy{at}dstl.gov.uk


  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 106 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.

Keywords: chemotherapy; fluoroquinolones; murine; quinolones; tularaemia.
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