Variation in Target Attainment of Beta-Lactam Antibiotic Dosing Between International Pediatric Formularies

Silke Gastine, Yingfen Hsia, Michelle Clements, Charlotte I.S. Barker, Julia Bielicki, Christine Hartmann, Mike Sharland, Joseph F. Standing*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)
27 Downloads (Pure)

Abstract

As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. Beta-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dosing recommendations from the major pediatric reference sources and tries to answer the questions: Does beta-lactam dose heterogeneity matter? Does it impact pharmacodynamic target attainment? For three important severe clinical infections—pneumonia, sepsis, and meningitis—pharmacokinetic models were identified for common for beta-lactam antibiotics. Real-world demographics were derived from three multicenter point prevalence surveys. Simulation results were compared with minimum inhibitory concentration distributions to inform appropriateness of recommended doses in targeted and empiric treatment. While cephalosporin dosing regimens are largely adequate for target attainment, they also pose the most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin, and meropenem doses as potentially requiring review/optimization in order to preserve the use of these agents in future.

Original languageEnglish
Pages (from-to)958-970
Number of pages13
JournalClinical Pharmacology and Therapeutics
Volume109
Issue number4
Early online date28 Feb 2021
DOIs
Publication statusPublished - 26 Apr 2021

Bibliographical note

Funding Information:
S.G.’s postdoctoral fellowship is funded by Global Antibiotic Research and Development Partnership (GARDP). C.I.S.B. is funded by the National Institute for Health Research (NIHR) as an Academic Clinical Fellow. S.G., C.I.S.B., and J.F.S. have been supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. C.I.S.B. is also supported by the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. J.F.S. received a UK Medical Research Council fellowship (MR/M008665/1). M.C. is supported by core support from the Medical Research Council UK to the MRC Clinical Trials Unit (MC_UU_12023/22).

Publisher Copyright:
© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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