title: Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.
abstract: Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent.
  
  
  
  This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.
authors.affiliation: a Division of Infectious Diseases and HIV Medicine, Department of Medicine , University of Cape Town , Cape Town , South Africa.
authors.forename: Sean
authors.initials: S
authors.lastname: Wasserman
authors.affiliation: a Division of Infectious Diseases and HIV Medicine, Department of Medicine , University of Cape Town , Cape Town , South Africa.|b Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences , University of Cape Town , Cape Town , South Africa.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: c Division of Clinical Pharmacology, Department of Medicine , University of Cape Town , Cape Town , South Africa.
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D017410:Practice Guidelines as Topic; D011485:Protein Binding; D043922:Toxicogenetics; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D000069349:Linezolid
keywords: Drug-resistant tuberculosis; linezolid; mitochondrial toxicity; oxazolidinones; pharmacogenomics; pharmacokinetics; therapeutic drug monitoring