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Antimicrobial Agents and Chemotherapy, October 1999, p. 2356-2360, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evaluation of Rifapentine in Long-Term Treatment Regimens for Tuberculosis in Mice

Anne M. J. A. Lenaerts, Sharon E. Chase, Alex J. Chmielewski, and Michael H. Cynamon*

Department of Medicine, Veterans Affairs Medical Center, and Department of Medicine, State University of New York Health Science Center, Syracuse, New York

Received 12 May 1999/Returned for modification 15 June 1999/Accepted 23 July 1999

Besides direct bactericidal activity, long-term effectiveness is one of the most important features to consider when developing new drugs for chemotherapy. In this study, we evaluated the ability of rifapentine (RFP), in monotherapy and combination therapy, to completely eradicate a Mycobacterium tuberculosis infection and to prevent relapse posttreatment in a Swiss mouse model. The combination of RFP, isoniazid (INH), and pyrazinamide (PZA) administered daily resulted in an apparent clearance of M. tuberculosis organisms in the lungs and spleens of infected mice after 10 weeks of treatment. However, 3 months after the cessation of therapy, bacterial regrowth occurred in mice treated for a 12-week period, indicating a relapse of infection. In intermittent treatment regimens of RFP in combination with INH and PZA, sterilization was achieved when mice were treated two to five times per week for 9 weeks. Bacterial growth was still observed in the once-weekly treatment group. Our results show that mouse models can predict important parameters for new drugs. We stress the necessity for long-term posttreatment observation in animal models for the routine evaluation of new drugs for antituberculosis chemotherapy.

* Corresponding author. Mailing address: VAMC, 800 Irving Ave., Syracuse, NY 13210. Phone: (315) 476-7461, ext. 3324. Fax: (315) 476-5348. E-mail: Cynamon.Michael{at}syracuse.va.gov.

Antimicrobial Agents and Chemotherapy, October 1999, p. 2356-2360, Vol. 43, No. 10
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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