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Dose-Ranging Comparison of Rifampin and Rifapentine in Two Pathologically Distinct Murine Models of Tuberculosis
- Source :
- Antimicrobial Agents and Chemotherapy; May 2012, Vol. 56 Issue: 8 p4331-4340, 10p
- Publication Year :
- 2012
-
Abstract
- ABSTRACTIn previous experiments, replacing the 10-mg/kg of body weight daily dose of rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in BALB/c mice by approximately 50% due to rifapentine's more potent activity and greater drug exposures obtained. In the present study, we performed dose-ranging comparisons of the bactericidal and sterilizing activities of rifampin and rifapentine, alone and in combination with isoniazid and pyrazinamide with or without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic lung granulomas after infection with Mycobacterium tuberculosis. Each rifamycin demonstrated a significant increase in sterilizing activity with increasing dose. Rifapentine was roughly 4 times more potent in both mouse strains. These results reinforce the rationale for ongoing clinical trials to ascertain the highest well-tolerated doses of rifampin and rifapentine. This study also provides an important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice, a strain in which the lung lesions observed after M. tuberculosisinfection may better represent the pathology of human tuberculosis.
Details
- Language :
- English
- ISSN :
- 00664804 and 10986596
- Volume :
- 56
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Antimicrobial Agents and Chemotherapy
- Publication Type :
- Periodical
- Accession number :
- ejs27945256
- Full Text :
- https://doi.org/10.1128/AAC.00912-12