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- Title
β-Lactam antimicrobial pharmacokinetics and target attainment in critically ill patients aged 1 day to 90 years: the ABDose study.
- Authors
Lonsdale, Dagan O; Kipper, Karin; Baker, Emma H; Barker, Charlotte I S; Oldfield, Isobel; Philips, Barbara J; Johnston, Atholl; Rhodes, Andrew; Sharland, Mike; Standing, Joseph F
- Abstract
<bold>Background: </bold>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.<bold>Patients and Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
UNITED Kingdom; PHARMACOKINETICS; CRITICALLY ill; BETA lactam antibiotics; LACTAMS; GESTATIONAL age; NEWBORN infants; ANTIBIOTICS; RESEARCH; RESEARCH methodology; ARTHRITIS Impact Measurement Scales; MEDICAL cooperation; EVALUATION research; CATASTROPHIC illness; COMPARATIVE studies; RESEARCH funding; LONGITUDINAL method; MICROBIAL sensitivity tests
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2020, Vol 75, Issue 12, p3625
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkaa363