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β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study

Lonsdale, DO; Kipper, K; Baker, EH; Barker, CIS; Oldfield, I; Philips, BJ; Johnston, A; ... Standing, JF; + view all (2020) β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study. Journal of Antimicrobial Chemotherapy , 75 (12) pp. 3625-3634. 10.1093/jac/dkaa363. Green open access

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Abstract

Background: The pharmacokinetics of β-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used β-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life β-lactam pharmacokinetic model and describe the extent to which standard doses achieve pharmacokinetic/pharmacodynamic targets associated with clinical cure. / Patients and methods: A total of 212 critically ill participants with an age range from 1 day (gestational age 24 weeks) to 90 years were recruited from a UK hospital, providing 1339 pharmacokinetic samples. Population pharmacokinetic analysis was undertaken using non-linear mixed-effects modelling (NONMEM) for each drug. Pooled data were used to estimate maturation and decline of β-lactam pharmacokinetics throughout life. / Results: Pharmacokinetic models for eight drugs were described, including what is thought to be the first benzylpenicillin model in critically ill adults. We estimate that 50% of adult β-lactam clearance is achieved by 43 weeks post-menstrual age (chronological plus gestational age). Fifty percent of decline from peak adult clearance occurs by 71 years. Paediatric participants were significantly less likely than adults to achieve pharmacokinetic/pharmacodynamic targets with standard antibiotic doses (P < 0.01). / Conclusions: We believe this to be the first prospective whole-life antibiotic pharmacokinetic study in the critically ill. The study provides further evidence that standard antibiotic doses fail to achieve pharmacokinetic/pharmacodynamic targets associated with clinical success in adults, children and neonates. Maturation and decline parameters estimated from this study could be adopted as a standard for future prospective studies.

Type: Article
Title: β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dkaa363
Publisher version: https://doi.org/10.1093/jac/dkaa363
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: antibiotics, penicillin g, drug clearance, adult, child, critical illness, gestational age, newborn, lactams, menstruation, pediatrics, pharmacokinetics, pharmacodynamics, antimicrobials, older adult
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10113051
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