Abstract
Clofazimine and high-dose rifapentine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.
Original language | English (US) |
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Article number | e00388-19 |
Journal | Antimicrobial agents and chemotherapy |
Volume | 63 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2019 |
Keywords
- BALB/c mice
- C3HeB/FeJ mice
- Clofazimine
- Mouse models
- Rifapentine
- Tuberculosis
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases