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- Title
Dose optimization of piperacillin/tazobactam in critically ill children.
- 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; Walle, Johan Vande; Pasqua, Oscar E. Della; De Paepe, Peter; Vande Walle, Johan; Della Pasqua, Oscar E
- Abstract
<bold>Objectives: </bold>To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.<bold>Patients and methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
CRITICALLY ill children; PIPERACILLIN; TAZOBACTAM; BETA-lactamase inhibitors; PHARMACOKINETICS; CRITICAL care medicine; ANTIBIOTICS; BACTERIAL diseases; CATASTROPHIC illness; DRUG administration; DOSE-effect relationship in pharmacology; INTRAVENOUS therapy; LONGITUDINAL method; PENICILLIN; MICROBIAL sensitivity tests; SYSTEM analysis; AMPICILLIN
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2017, Vol 72, Issue 7, p2002
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkx093