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Antimicrobial Agents and Chemotherapy, October 1999, p. 2356-2360, Vol. 43, No. 10
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.
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
*
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.
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