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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

May 7, 2025
Antimicrob Agents Chemother
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Authors

Nathan Peroutka-Bigus 1, Elizabeth J Brooks 1, Michelle E Ramey 1, Hope D'Erasmo 2, Jackie P Ernest 3, Allison A Bauman 1, Lisa K Woolhiser 1, Radojka M Savic 3, Anne J Lenaerts 1, Bree B Aldridge 2 4 5, Jansy P Sarathy 6 7, Gregory T Robertson 1

Nathan Peroutka-Bigus
,
Elizabeth J Brooks
,
Michelle E Ramey
,
Hope D'Erasmo
,
Jackie P Ernest
,
Allison A Bauman
,
Lisa K Woolhiser
,
Rada Savic
,
Anne J Lenaerts
,
Bree B Aldridge
,
Jansy P Sarathy
,
Gregory T Robertson
,

Matthew J Reichlen 123,  Emmanuel Musisi 234, Samuel T Tabor 23, Holly Nielsen 23, Ashley M Gerwing 4, Firat Kaya 5, Matthew Zimmerman 5, Martin I Voskuil 12, Gregory T Robertson 24, Nicholas D Walter 236

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.

Keywords: C3HeB/FeJ; caseum; relapse; rifafour; tuberculosis.

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