Contribution of front-line, standard-of-care drugs to bactericidal responses, resistance emergence, and cure in murine models of easy- or hard-to-treat tuberculosis disease
Peroutka-Bigus N, Brooks EJ, Ramey ME, D'Erasmo H, Ernest JP, Bauman AA, Woolhiser LK, Savic RM, et al. (12 authors)
Antimicrobial agents and chemotherapy · 2025-03
Abstract
By assessing the standard-of-care regimen for tuberculosis (TB) in BALB/c and C3HeB/FeJ mice, we demonstrate that rifampin, with or without pyrazinamide, is essential for an effective bactericidal response and suppression of resistance. Potency measurements in an in vitro lipid-rich model and a rabbit caseum assay recapitulate the significance of rifampin as a sterilizing agent. These outcomes align with clinical performance, thus emphasizing the value of in vitro predictive tools and murine TB models with human-like pathology.
MeSH terms
- Animals
- Mice, Inbred BALB C
- Mice, Inbred C3H
- Rabbits
- Mice
- Mycobacterium tuberculosis
- Tuberculosis
- Disease Models, Animal
- Pyrazinamide
- Rifampin
- Antitubercular Agents
- Microbial Sensitivity Tests
- Drug Resistance, Bacterial
- Female