Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy

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• dc.contributor.author Butragueño-Laiseca, Laura
• dc.contributor.author Marco-Ariño, Nicolás
• dc.contributor.author Troconiz, Iñaki F.
• dc.contributor.author Grau Cerrato, Santiago
• dc.contributor.author Campillo Ambrós, Núria
• dc.contributor.author García, Xandra
• dc.contributor.author Padilla, Belén
• dc.contributor.author Fernández, Sarah Nicole
• dc.contributor.author Slöcker, María
• dc.contributor.author Santiago, María José
• dc.date.accessioned 2024-05-03T05:53:53Z
• dc.date.available 2024-05-03T05:53:53Z
• dc.date.issued 2022
• dc.description.abstract Objectives: Despite that piperacillin-tazobactam combination is commonly used in critically ill children, increasing evidence suggests that the current dosing schedules are not optimal for these patients. The aim of this work is to develop a population pharmacokinetic model for piperacillin to evaluate the efficacy of standard dosing in children with and without continuous kidney replacement therapy (CKRT) and to propose alternative dosing schemes maximizing target attainment. Methods: Four hundred twenty-nine piperacillin concentrations measured in different matrices, obtained from 32 critically ill children (19 without CKRT, 13 with CKRT) receiving 100 mg/kg of piperacillin/tazobactam every 8 hours (increased to 12 hours after the fourth dose) were modelled simultaneously using the population approach with NONMEM 7.4. The percentage of patients with 90% fT > MIC and target attainment (percentage of dosing interval above MIC) were estimated for different intermittent and continuous infusions in the studied population. Results: Piperacillin pharmacokinetic was best described with a two-compartment model. Renal, nonrenal, and hemofilter clearances were found to be influenced by the glomerular filtration rate, height (renal clearance), weight (nonrenal clearance), and filter surface (hemofilter clearance). Only seven (37%) children without CKRT and seven (54%) with CKRT achieved 90% fT > MIC with the current dosing schedule. Of the alternative regimens evaluated, a 24-hour continuous infusion of 200 mg/kg (CKRT) and 300 mg/kg (no CKRT) provided 100% fT > MIC (percent of time free drug remains above the minimum inhibitory concentration) (≤16 mg/L) and target attainments ≥90% across all evaluated MICs. Discussion: In children with and without CKRT, standard dosing failed to provide an adequate systemic exposure, while prolonged and continuous infusions showed an improved efficacy.
• dc.format.mimetype application/pdf
• dc.identifier.citation Butragueño-Laiseca L, Marco-Ariño N, Troconiz IF, Grau S, Campillo N, García X, et al. Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy. Clin Microbiol Infect. 2022 Sep;28(9):1287.e9-1287.e15. DOI: 10.1016/j.cmi.2022.03.031
• dc.identifier.doi http://dx.doi.org/10.1016/j.cmi.2022.03.031
• dc.identifier.issn 1198-743X
• dc.identifier.uri http://hdl.handle.net/10230/59980
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Clin Microbiol Infect. 2022 Sep;28(9):1287.e9-1287.e15
• dc.rights © 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Acute kidney injury
• dc.subject.keyword Continuous renal replacement therapy
• dc.subject.keyword Critically ill children
• dc.subject.keyword Dose individualization
• dc.subject.keyword Piperacillin
• dc.subject.keyword Population pharmacokinetics
• dc.subject.keyword Tazobactam
• dc.title Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion