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

Lonsdale, Dagan O, Kipper, Karin, Baker, Emma H, Barker, Charlotte I S, Oldfield, Isobel, Philips, Barbara J, Johnston, Atholl, Rhodes, Andrew, Sharland, Mike and Standing, Joseph F (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

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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
Keywords: Adult, Aged, Anti-Bacterial Agents, Child, Critical Illness, Humans, Infant, Newborn, Microbial Sensitivity Tests, Prospective Studies, beta-Lactams
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 10 Nov 2021 10:16
Last Modified: 07 Jan 2022 15:25
URI: http://sro.sussex.ac.uk/id/eprint/102769

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