Dataset Information

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

ABSTRACT: Objectives:The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods:We defined linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119?mg/L/h) and safety (fCmin <1.38?mg/L). We extracted individual-level linezolid PK data from existing studies on TB patients and performed meta-analysis, producing summary estimates of fAUC0-24 and fCmin for published doses. Combining these with a published MIC distribution, we performed Monte Carlo simulations of target attainment. Results:The efficacy target was attained in all simulated individuals at 300?mg q12h and 600?mg q12h, but only 20.7% missed the safety target at 300?mg q12h versus 98.5% at 600?mg q12h. Although suggesting 300?mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300?mg q24h and by 44.6% and 27.5%, respectively, at 600?mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable. Conclusions:Linezolid dosing at 300?mg q12h may retain the efficacy of the 600?mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300?mg q24h and 600?mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required.

SUBMITTER: Millard J

PROVIDER: S-EPMC6005026 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

Millard James J Pertinez Henry H Bonnett Laura L Hodel Eva Maria EM Dartois Véronique V Johnson John L JL Caws Maxine M Tiberi Simon S Bolhuis Mathieu M Alffenaar Jan-Willem C JC Davies Geraint G Sloan Derek J DJ

The Journal of antimicrobial chemotherapy 20180701 7

<h4>Objectives</h4>The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimum dose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap.<h4>Methods</h4>We defined linezolid PK/PD targets for efficacy (fAUC0-24:MIC >119 mg/L/h) and safety (fCmin <1.38 mg/L). We extracted individual-level linezolid PK data from existing studies on TB pa ...[more]

PMID: 29584861

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Dataset Information

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

Publications

Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation.

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