Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy.

ABSTRACT:

Unlabelled

Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but mor

SUBMITTER: Brown AN 

PROVIDER: S-EPMC4631805 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature