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

Background The pharmacokinetics of ß-lactam antibiotics in critical illness remain poorly characterized, particularly in neonates, children and the elderly. We undertook a pharmacokinetic study of commonly used ß-lactam antibiotics in critically ill patients of all ages. The aims were to produce a whole-life ß-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 ß-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 ß-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?