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.

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.