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Population pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis.
Bui, S; Facchin, A; Ha, P; Bouchet, S; Leroux, S; Nacka, F; Fayon, M; Jacqz-Aigrain, E.
Affiliation
  • Bui S; Centre d'Investigation Clinique (CIC1401), Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Centre de Recherche Cardio-thoracique de Bordeaux (U1045), Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, France.
  • Facchin A; Département de Pharmacologie Pédiatrique et Pharmacogénétique, Centre Hospitalier Universitaire Robert Debré APHP, Paris, France.
  • Ha P; Service de Pharmacie, Centre hospitalier Intercommunal Robert Ballanger, Aulnay-sous-Bois, France.
  • Bouchet S; Université de Paris, Paris, France.
  • Leroux S; Département de Pharmacologie Pédiatrique et Pharmacogénétique, Centre Hospitalier Universitaire Robert Debré APHP, Paris, France.
  • Nacka F; Département de Pharmacologie et de toxicologie, Centre Hospitalier Universitaire de Bordeaux, Groupe hospitalier Pellegrin, Bordeaux, France.
  • Fayon M; Département de Pharmacologie Pédiatrique et Pharmacogénétique, Centre Hospitalier Universitaire Robert Debré APHP, Paris, France.
  • Jacqz-Aigrain E; Centre d'Investigation Clinique (CIC1401), Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Centre de Recherche Cardio-thoracique de Bordeaux (U1045), Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, France.
J Antimicrob Chemother ; 75(8): 2232-2239, 2020 08 01.
Article in En | MEDLINE | ID: mdl-32457995
ABSTRACT

BACKGROUND:

Pharmacokinetics data on ceftazidime are sparse for the paediatric population, particularly for children with cystic fibrosis (CF) or severe infections.

OBJECTIVES:

To characterize the population pharmacokinetics of ceftazidime in critically ill children, identify covariates that affect drug disposition and evaluate the current dosing regimens.

METHODS:

The study was registered with Clinicaltrials.gov (NCT01344512). Children receiving ceftazidime were selected in 13 French hospitals. Plasma concentrations were determined by UPLC-MS/MS. Population pharmacokinetic analyses were performed using NONMEN software.

RESULTS:

One hundred and eight patients, aged 28 days to 12 years, with CF (n = 32), haematology and/or oncology disorders (n = 47) or severe infection (n = 29) were included. Ceftazidime was administered by continuous or intermittent infusions; 271 samples were available for analysis. A two-compartment model with first-order elimination and allometric scaling was developed and covariate analysis showed that ceftazidime pharmacokinetics were also significantly affected by CLCR and CF. Ceftazidime clearance was 82% higher in CF than in non-CF patients. Monte Carlo simulations showed that the percentage of target attainment (PTA) for the target of T>MIC = 65% was (i) lower in CF than in non-CF children with intermittent infusions and (ii) higher with continuous than intermittent infusion in all children.

CONCLUSIONS:

The population pharmacokinetics model for ceftazidime in children was influenced by body weight, CLCR and CF. A higher PTA was obtained with continuous versus intermittent infusions. Further studies should explore the benefits of continuous versus intermittent infusion of ceftazidime, including current versus increased doses in CF children.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ceftazidime / Cystic Fibrosis Type of study: Health_economic_evaluation Limits: Child / Humans Language: En Journal: J Antimicrob Chemother Year: 2020 Document type: Article Affiliation country: Francia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ceftazidime / Cystic Fibrosis Type of study: Health_economic_evaluation Limits: Child / Humans Language: En Journal: J Antimicrob Chemother Year: 2020 Document type: Article Affiliation country: Francia