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Dose optimization of piperacillin/tazobactam in critically ill children

De Cock, P; Van Dijkman, S; De Jaeger, A; Willems, J; Carlier, M; Verstraete, A; Delanghe, J; ... De Paepe, P; + view all (2017) Dose optimization of piperacillin/tazobactam in critically ill children. Journal of Antimicrobial Chemotherapy , 72 (7) pp. 2002-2011. 10.1093/jac/dkx093. Green open access

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Abstract

Objectives: To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen. / Patients and methods: 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. / Results: 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% fT>MIC >16 mg/L). / Conclusions: 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.

Type: Article
Title: Dose optimization of piperacillin/tazobactam in critically ill children
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dkx093
Publisher version: https://doi.org/10.1093/jac/dkx093
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: drug clearance, child, critical illness, infant, pediatric intensive care unit, piperacillin, infection, pharmacokinetics, drug loading dose, piperacillin-tazobactam, critically ill children, intravenous infusion, continuous, infusion procedures
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1543303
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