Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing

Author:

Reza Nada12ORCID,Gerada Alessandro12ORCID,Stott Katharine E.12ORCID,Howard Alex12,Sharland Mike3ORCID,Hope William12ORCID

Affiliation:

1. Department of Antimicrobial Pharmacodynamics and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom

2. Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom

3. Centre for Neonatal and Paediatric Infection, Institute for Infection and Immunity, St George’s, University of London, London, United Kingdom

Abstract

SUMMARY The World Health Organisation’s 2022 AWaRe Book provides guidance for the use of 39 antibiotics to treat 35 infections in primary healthcare and hospital facilities. We review the evidence underpinning suggested dosing regimens. Few ( n = 18) population pharmacokinetic studies exist for key oral AWaRe antibiotics, largely conducted in homogenous and unrepresentative populations hindering robust estimates of drug exposures. Databases of minimum inhibitory concentration distributions are limited, especially for community pathogen-antibiotic combinations. Minimum inhibitory concentration data sources are not routinely reported and lack regional diversity and community representation. Of studies defining a pharmacodynamic target for ß-lactams ( n = 80), 42 (52.5%) differed from traditionally accepted 30%–50% time above minimum inhibitory concentration targets. Heterogeneity in model systems and pharmacodynamic endpoints is common, and models generally use intravenous ß-lactams. One-size-fits-all pharmacodynamic targets are used for regimen planning despite complexity in drug-pathogen-disease combinations. We present solutions to enable the development of global evidence-based antibiotic dosing guidance that provides adequate treatment in the context of the increasing prevalence of antimicrobial resistance and, moreover, minimizes the emergence of resistance.

Funder

Wellcome Trust

Publisher

American Society for Microbiology

Reference135 articles.

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