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

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Data availability

The data that supports the findings of this study are available in the supplementary material of this article.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Brianna Kispal

    Present address: Department of Pharmacy, Kingston General Hospital, 76 Stuart St, Kingston, Ontario, K7L 2V7, Canada

Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St, Toronto, Ontario, M5S 3M2, Canada

    Brianna Kispal & Sandra A. N. Walker

  2. Department of Pharmacy Bayview Campus, Sunnybrook Health Sciences Center (SHSC), 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada

    Sandra A. N. Walker

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  1. Brianna Kispal
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Brianna Kispal: data collection, data analysis, manuscript development; Sandra Walker: project supervisor, study conceptualization, methods development, data analysis, manuscript development.

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Correspondence to Sandra A. N. Walker.

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Kispal, B., Walker, S.A.N. Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults. Eur J Clin Pharmacol 77, 197–205 (2021). https://doi.org/10.1007/s00228-020-02998-7

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