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Population pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis

dc.rights.licenseopenen_US
dc.contributor.authorBUI, Stephanie
dc.contributor.authorFACCHIN, A.
dc.contributor.authorHA, P.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUCHET, Stephane
dc.contributor.authorLEROUX, S.
dc.contributor.authorNACKA, F.
dc.contributor.authorFAYON, M.
dc.contributor.authorJACQZ-AIGRAIN, E.
dc.date.accessioned2021-01-18T13:40:33Z
dc.date.available2021-01-18T13:40:33Z
dc.date.issued2020
dc.identifier.issn1460-2091 (Electronic) 0305-7453 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/25827
dc.description.abstractEnBackground 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.
dc.language.isoENen_US
dc.subjectPharmacoEpi-Drugs
dc.title.enPopulation pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis
dc.title.alternativeJ Antimicrob Chemotheren_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/jac/dkaa170en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32457995en_US
bordeaux.journalJournal of Antimicrobial Chemotherapyen_US
bordeaux.page2232-2239en_US
bordeaux.volume75en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue8en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamPharmacoEpi-Drugsen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03166186
hal.version1
hal.date.transferred2021-03-11T09:32:03Z
hal.exporttrue
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