Efficacy Versus Hepatotoxicity of High-dose Rifampin, Pyrazinamide, and Moxifloxacin to Shorten Tuberculosis Therapy Duration: There Is Still Fight in the Old Warriors Yet!

ABSTRACT:

Background

One approach that could increase the efficacy and reduce the duration of antituberculosis therapy is pharmacokinetics/pharmacodynamics-based optimization of doses. However, this could increase toxicity.

Methods

We mimicked the concentration-time profiles achieved by human equivalent doses of moxifloxacin 800 mg/day, rifampin 1800 mg/day, and pyrazinamide 4000 mg/day (high-dose regimen) vs isoniazid 300 mg/day, rifampin 600 mg/day, and pyrazinamide 2000 mg/day (standard therapy) in bactericidal and sterilizing effect studies in the hollow fiber system model of tuberculosis (HFS-TB). In an intracellular Mycobacterium tuberculosis (Mtb) HFS-TB experiment, we added a 3-dimensional human organotypic liver to determine potential hepatotoxicity of the high-dose regimen,

SUBMITTER: Srivastava S 

PROVIDER: S-EPMC6260156 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature