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JAC Advance Access originally published online on October 13, 2005
Journal of Antimicrobial Chemotherapy 2005 56(6):1069-1073; 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.

In vivo efficacy of fluoroquinolones against systemic tularaemia infection in mice

T. Piercy1,*, J. Steward1, M. S. Lever1 and T. J. G. Brooks1,2

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

Received 3 May 2005; returned 25 June 2005; revised 9 September 2005; accepted 9 September 2005

* Correspondence address. Room 14, Bldg 245, Dstl Porton Down, Salisbury, Wiltshire SP4 OJQ, UK. Tel: +44-1980-613221; Fax: +44-1980-613284; E-mail: tjpiercy{at}dstl.gov.uk

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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