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

TL;DR

This study shows that rifampin is crucial for treating tuberculosis in mice and preventing drug resistance.

Contribution

The study identifies rifampin's essential role in bactericidal activity and resistance suppression in TB treatment.

Findings

Rifampin, with or without pyrazinamide, is essential for effective bactericidal responses.

In vitro models and rabbit assays confirm rifampin's sterilizing effect in TB treatment.

Murine TB models with human-like pathology align with clinical outcomes.

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.

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