Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis.

ABSTRACT:

Background

Linezolid (LZD) is bactericidal against Mycobacterium tuberculosis, but it has treatment-limiting toxicities. A better understanding of exposure-response relationships governing LZD efficacy and toxicity will inform dosing strategies. Because in vitro monotherapy studies yielded conflicting results, we explored LZD pharmacokinetic/pharmacodynamic (PK/PD) relationships in vivo against actively and nonactively multiplying bacteria, including in combination with pretomanid.

Methods

Linezolid multidose pharmacokinetics were modeled in mice. Dose-fractionation studies were performed in acute (net bacterial growth) and chronic (no net growth) infection models. In acute models, LZD was administered alone or with bacteriostatic or bactericidal pretomanid doses. Correlatio

SUBMITTER: Bigelow KM 

PROVIDER: S-EPMC8176636 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature