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JAC Advance Access originally published online on June 8, 2007
Journal of Antimicrobial Chemotherapy 2007 60(2):429-432; doi:10.1093/jac/dkm200
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Gatifloxacin in combination with rifampicin in a murine tuberculosis model

Michael Cynamon*, Mary R. Sklaney and Carolyn Shoen

Veterans Affairs Medical Center, 800 Irving Avenue, Syracuse, NY 13210, USA

Received 7 February 2007; returned 13 March 2007; revised 8 May 2007; accepted 10 May 2007

* Corresponding author. Tel: +1-315-425-4884; Fax: +1-315-425-4871; E-mail: michael.cynamon{at}med.va.gov

Objectives: Gatifloxacin previously demonstrated good in vitro and in vivo activities against Mycobacterium tuberculosis. Several regimens of gatifloxacin in combination with rifampicin were compared with isoniazid plus rifampicin in a mouse tuberculosis model.

Methods: C57BL/6 mice were infected intranasally with ~106 viable M. tuberculosis organisms. Treatment with various regimens of gatifloxacin plus rifampicin was started 1 week post-infection and was administered for 4–12 weeks. Mice were euthanized at the end of therapy and their right lungs were removed and cell counts were determined.

Results: Gatifloxacin 100 mg/kg plus rifampicin 10 mg/kg has activity similar to that of isoniazid plus rifampicin in the 12 week treatment model. Gatifloxacin 300 mg/kg plus rifampicin 20 mg/kg yields a non-cultivatable state after 12 weeks of therapy and approaches but does not achieve a durable cure.

Conclusions: Gatifloxacin in combination with rifampicin is a promising combination for potential evaluation in human clinical trials. Gatifloxacin plus rifampicin regimens had activities similar to or better than isoniazid plus rifampicin. A quinolone plus rifampicin combination may provide the foundation for shorter course regimens than the current isoniazid plus rifampicin-based regimen.

Keywords: Mycobacterium tuberculosis , mycobacteria , TB , pulmonary , antimycobacterial agents


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