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Open Access Evolving strategies for dose optimization of linezolid for treatment of tuberculosis

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The role of linezolid (LZD) in the management of drug-resistant tuberculosis is evolving. Optimizing its usage to maximize efficacy while minimizing its toxicity requires greater understanding of the relationships between drug exposure and bacterial killing, resistance suppression and toxicity. Recent non-clinical and clinical studies provide some useful insights and are reviewed here. Because LZD toxicity is dose- and duration-dependent, and is driven by elevated trough concentrations and prolonged exposure to concentrations inhibiting mitochondrial protein synthesis, several innovative dosing strategies can be employed to optimize its usage. These strategies, which are not mutually exclusive, may include giving higher doses more intermittently, giving higher daily doses for shorter durations, and giving lower total durations. For example, one approach may involve daily doses of 900–1200 mg for the first 1–3 months of treatment, followed by intermittent (e.g., thrice-weekly) dosing of 1200 mg. Trials to evaluate regimens based on such strategies are required.
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Keywords: linezolid; multidrug-resistant tuberculosis; oxazolidinone; pharmacodynamics; sutezolid

Document Type: Research Article

Affiliations: Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Publication date: December 1, 2016

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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