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JAC Advance Access published online on February 24, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki039
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JAC © British Crown Copyright 2005, Dstl-published with the permission of the Controller of Her Majesty's Stationery Office.
Received July 13, 2004
Revised November 23, 2004
Accepted December 30, 2004

Original article

Comparison of gatifloxacin, moxifloxacin and ciprofloxacin for treatment of experimental Burkholderia pseudomallei infection

J. Steward 1*, T. Piercy 1, M. S. Lever 1, M. Nelson 1, A. J. H. Simpson 2, and T. J. G. Brooks 3

1 Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK
2 Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK; Department of Medical Microbiology, Royal Free and University College Medical School, University College London, London, UK
3 Biomedical Sciences, Dstl Porton Down, Salisbury SP4 OJQ, UK; HPA Porton Down, Salisbury SP4 OJG, UK

* To whom correspondence should be addressed.
J. Steward, E-mail: jasteward{at}dstl.gov.uk


  Abstract

Objectives: 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 106 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.

Keywords: melioidosis; murine; chemotherapy; fluoroquinolones.
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S. P. Sivalingam, S. H. Sim, L. C. W. Jasper, D. Wang, Y. Liu, and E. E. Ooi
Pre- and post-exposure prophylaxis of experimental Burkholderia pseudomallei infection with doxycycline, amoxicillin/clavulanic acid and co-trimoxazole
J. Antimicrob. Chemother., March 1, 2008; 61(3): 674 - 678.
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