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
Nathan Peroutka‐BigusiD, Elizabeth J. Brooks, Michelle E. Ramey, Hope D’ErasmoiD, Jacqueline P. ErnestiD, Allison BaumaniD, Lisa K. Woolhiser, Radojka M. SavićiD, Anne J. M. Lenaerts, Bree B. AldridgeiD, Jansy Passiflora SarathyiD, Gregory T. RobertsoniD
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 to effective bactericidal response and resistance suppression. Potency measurements in an in vitro lipid-rich model and 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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