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
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 <i>in vitro</i> 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 <i>in vitro</i> predictive tools and murine TB models with human-like pathology.
Authors
- Elizabeth J. Brooks
- Gregory T. Robertson (ORCID: https://orcid.org/0000-0001-7157-4034)
- Radojka M. Savić (ORCID: https://orcid.org/0000-0003-3143-5579)
- Lisa K. Woolhiser
- Allison Bauman (ORCID: https://orcid.org/0000-0002-7925-3099)
- Jacqueline P. Ernest (ORCID: https://orcid.org/0000-0002-7664-7287)
- Anne J. Lenaerts
- Bree B. Aldridge (ORCID: https://orcid.org/0000-0003-2236-1424)
- Jansy Passiflora Sarathy (ORCID: https://orcid.org/0000-0002-1532-146X)
- Nathan Peroutka‐Bigus (ORCID: https://orcid.org/0000-0001-5212-9541)
- Michelle E. Ramey
- Hope D’Erasmo
Institutions
- Tufts University (US)
- University of California, San Francisco (US)
- Hackensack Meridian Health (US)
- Center for Discovery (US)
- Colorado State University (US)
Publication Details
- Journal
- Antimicrobial Agents and Chemotherapy
- Published
- 2025-03-26
- DOI
- https://doi.org/10.1128/aac.01901-24
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Bill and Melinda Gates Foundation
- National Institute of Allergy and Infectious Diseases