Dose optimization of piperacillin/tazobactam in critically ill children

To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 r...

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Published in:Journal of antimicrobial chemotherapy 2017-07, Vol.72 (7), p.2002-2011
Main Authors: De Cock, Pieter A J G, van Dijkman, Sven C, de Jaeger, Annick, Willems, Jef, Carlier, Mieke, Verstraete, Alain G, Delanghe, Joris R, Robays, Hugo, Vande Walle, Johan, Della Pasqua, Oscar E, De Paepe, Peter
Format: Article
Language:English
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Summary:To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg every 6 h based on piperacillin). Piperacillin/tazobactam concentrations were measured by an LC-MS/MS method. Pharmacokinetic data were analysed using non-linear mixed effects modelling. Piperacillin and tazobactam blood samples were collected from 47 patients (median age 2.83 years; range 2 months to 15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model that included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) every 4 h over 2 h, 100 mg/kg every 4 h given over 1 h or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24 h were the minimal requirements to achieve the therapeutic targets for piperacillin (60% f T >MIC >16 mg/L). Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkx093