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dc.contributor.authorCheng, V
dc.contributor.authorAbdul-Aziz, MH
dc.contributor.authorBurrows, F
dc.contributor.authorBuscher, H
dc.contributor.authorCho, YJ
dc.contributor.authorCorley, A
dc.contributor.authorDiehl, A
dc.contributor.authorGilder, E
dc.contributor.authorJakob, SM
dc.contributor.authorKim, HS
dc.contributor.authorLevkovich, BJ
dc.contributor.authorLim, SY
dc.contributor.authorMcGuinness, S
dc.contributor.authorParke, R
dc.contributor.authorFraser, John F.
dc.contributor.authoret al.
dc.date.accessioned2021-11-04T01:04:38Z
dc.date.available2021-11-04T01:04:38Z
dc.date.issued2021
dc.identifier.issn0066-4804
dc.identifier.doi10.1128/AAC.01438-21
dc.identifier.urihttp://hdl.handle.net/10072/409762
dc.description.abstractOur study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analyzed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (%fT.MIC) and toxic exposures of greater than 360 mg/liter. The tazobactam target of percentage of time free concentrations of.2 mg/liter was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models, with body mass index, creatinine clearance, and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5-g every 6 hours regimen administered over 4 hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/liter while exposing patients to a,3% probability of toxic concentrations. In patients receiving ECMO and RRT, a frequency reduction to every 12 hours dosing lowers the probability of toxic concentrations, although this remains at 7 to 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrome0143821
dc.relation.ispartofissue11
dc.relation.ispartofjournalAntimicrobial Agents and Chemotherapy
dc.relation.ispartofvolume65
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode3214
dc.subject.keywordsECMO
dc.subject.keywordsantibiotics
dc.subject.keywordscontinuous renal replacement therapy
dc.subject.keywordsdosing
dc.subject.keywordsneurotoxicity
dc.titlePopulation pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation: An ASAP ECMO study
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCheng, V; Abdul-Aziz, MH; Burrows, F; Buscher, H; Cho, YJ; Corley, A; Diehl, A; Gilder, E; Jakob, SM; Kim, HS; Levkovich, BJ; Lim, SY; McGuinness, S; Parke, R; Fraser, JF; et al., Population pharmacokinetics of piperacillin and tazobactam in critically ill patients receiving extracorporeal membrane oxygenation: An ASAP ECMO study, Antimicrobial Agents and Chemotherapy, 2021, 65 (11), pp. e0143821-
dc.date.updated2021-11-04T01:00:17Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
gro.hasfulltextFull Text
gro.griffith.authorFraser, John F.
gro.griffith.authorCorley, Amanda


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