Mohammed Rohi Sanoufi 1, Léo Froelicher-Bournaud 3, Mehdi Oualha 2, Seef ABDALLA 3, Steeve Rouillon 3, Jean-Marc Treluyera Treluyer 1,2,3, Frantz Foissac 2, Naïm Bouazza 2, Sihem Benaboud 1,2,3
1 Inserm, UMR1343, Pharmacologie et évaluations des thérapeutiques chez l'enfant et la femme enceinte, Université Paris Cité (Paris, France), 2 Unité de Recherche Clinique, Université Paris Cité Necker/Cochin, Hôpital Tarnier (Paris , France), 3 Service de pharmacologie périnatale, pédiatrique et adulte, AP-HP, Hôpital Cochin, rue du Faubourg-Saint-Jacques, F-75014 Paris, Hôpital Européen Georges Pompidou, rue Leblanc (Paris , France)
Introduction : Ceftazidime is a widely used antibiotic in the treatment of severe infections and cystic fibrosis (CF) in critically ill paediatric patients.
The objective of this study was to characterise the population pharmacokinetics of Ceftazidime in critically ill children, to identify significant covariates, and to optimise dosing regimens through Monte Carlo simulations to ensure adequate pharmacodynamic target attainment.
Methods: A population pharmacokinetics (popPK) study was conducted in 57 critically ill children (0.09–18 years) receiving intravenous Ceftazidime in seven paediatric departments, including intensive care units. A total of 246 plasma concentrations were measured by a validated HPLC–MS/MS method. The Concentration–time data were analysed using nonlinear mixed-effects modelling (Monolix, version 2024R1), and the impact of demographic and clinical covariates was tested. The selection of the model was based on goodness-of-fit, likelihood ratio tests, and predictive checks. The effects of covariates were evaluated through a stepwise forward inclusion and backward elimination. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for different dosing regimens at the EUCAST MIC breakpoint of 8 mg/L, with a PD target of 100% fT>MIC.
Results: Ceftazidime PK was best described by a one-compartment model with first-order elimination. Body weight (allometrically scaled) significantly improved the model fit. Clearance (CL) was further influenced by estimated glomerular filtration rate (eGFR) and cystic fibrosis status (CF). Simulations showed that standard intermittent infusion regimens frequently failed to achieve 100% fT>MIC, particularly in patients with high eGFR. In contrast, continuous infusion of 6 g/day consistently achieved >90% PTA across all simulated groups.
Conclusions: Ceftazidime pharmacokinetics in critically ill children are strongly influenced by body weight, renal function, and cystic fibrosis. Standard intermittent regimens may be insufficient, while continuous infusion provides the best target attainment.
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Reference: PAGE 34 (2026) Abstr 11991 [www.page-meeting.org/?abstract=11991]
Poster: Drug/Disease Modelling - Paediatrics