Lonsdale, DO; Kipper, K; Baker, EH; Barker, CIS; Oldfield, I; Philips, BJ; Johnston, A; Rhodes, A; Sharland, M; Standing, JF
(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.
ISSN 0305-7453
https://doi.org/10.1093/jac/dkaa363
SGUL Authors: Lonsdale, Dagan
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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.
Item Type: | Article | |||||||||||||||||||||
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Additional Information: | This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record Dagan O Lonsdale, Karin Kipper, Emma H Baker, Charlotte I S Barker, Isobel Oldfield, Barbara J Philips, Atholl Johnston, Andrew Rhodes, Mike Sharland, Joseph F Standing, β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study, Journal of Antimicrobial Chemotherapy, Volume 75, Issue 12, December 2020, Pages 3625–3634 is available online at: https://doi.org/10.1093/jac/dkaa363 The published version of this article can be accessed at: https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa363/5912705?guestAccessKey=b0ce7f83-f206-4d7b-898f-a55a1a48902b | |||||||||||||||||||||
Keywords: | 1115 Pharmacology and Pharmaceutical Sciences, 0605 Microbiology, 1108 Medical Microbiology, Microbiology | |||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical & Biomedical Education (IMBE) Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Journal of Antimicrobial Chemotherapy | |||||||||||||||||||||
ISSN: | 0305-7453 | |||||||||||||||||||||
Language: | en | |||||||||||||||||||||
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Publisher License: | Publisher's own licence | |||||||||||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/112435 | |||||||||||||||||||||
Publisher's version: | https://doi.org/10.1093/jac/dkaa363 |
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