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Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults.

Abstract：

PURPOSE:Tigecycline is one of few antibiotics active against multidrug-resistant bacteria; however, the assessment of dosing strategies to optimize its activity is needed. The purpose was to use Monte Carlo Simulation (MCS) to determine if safe tigecycline dosing options attaining breakpoints for pharmacokinetic/pharmacodynamic (PK-PD) targets in non-critically ill adults could be identified. METHODS:Publications that evaluated tigecycline dosing regimens and provided mean PK variables of interest (minimum 2 of: elimination rate constant or half-life and volume of distribution or clearance), with SDs, were included. Weighted mean (±SDs) for each PK parameter were determined. Food and Drug Administration minimum inhibitory concentration (MIC) tigecycline breakpoints for susceptible (MIC ≤ 2 μg/mL), intermediate (MIC 4 μg/mL), and resistant (MIC ≥ 8 μg/mL) Enterobacteriaceae were used. MCS probability distributions for PK-PD target attainment of AUC for total tigecycline plasma concentration from 0 to 24 h following an intravenous dose (AUCtotal, 0-24h) to MIC ratios of ≥ 18, 7, and 4.5 were generated, with success defined as ≥ 80% probability of target attainment at a given MIC. RESULTS:Ten studies (n = 442) were eligible. Tigecycline 150 mg IV q12h for ward patients with resistant bacteria up to a MIC of 0.48, 1, and 2 μg/mL for an AUCtotal, 0-24h/MIC target attainment of 18, 7, and 4.5, respectively, may be appropriate. CONCLUSION:Bacterial infections with tigecycline MICs ≥ 0.48-2 μg/mL, depending on AUCtotal, 0-24h/MIC target, may require treatment with alternate antibiotics due to target attainment failure.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Kispal B,Walker SAN

doi

10.1007/s00228-020-02998-7

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

197-205

issue

2

eissn

0031-6970

issn

1432-1041

pii

10.1007/s00228-020-02998-7

journal_volume

77

pub_type

杂志文章

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