Martínez Casanova, JavierEsteve Pitarch, ErikaColom Codina, HelenaGumucio Sanguino, Víctor DanielCobo Sacristán, SaraShaw, EvelynMaisterra Santos, KristelSabater Riera, JoanPérez Fernandez, Xosé L.Rigo Bonnin, RaúlTubau Quintano, FeCarratalà, JordiPadullés Zamora, Ariadna2023-05-232023-05-232023-03-072079-6382https://hdl.handle.net/2445/198337Critically ill patients undergo significant pathophysiological changes that affect antibiotic pharmacokinetics. Piperacillin/tazobactam administered by continuous infusion (CI) improves pharmacokinetic/pharmacodynamic (PK/PD) target attainment. This study aimed to characterize piperacillin PK after CI administration of piperacillin/tazobactam in critically ill adult patients with preserved renal function and to determine the empirical optimal dosing regimen. A total of 218 piperacillin concentrations from 106 patients were simultaneously analyzed through the population PK approach. A two-compartment linear model best described the data. Creatinine clearance (CLCR) estimated by CKD-EPI was the covariate, the most predictive factor of piperacillin clearance (CL) interindividual variability. The mean (relative standard error) parameter estimates for the final model were: CL: 12.0 L/h (6.03%); central and peripheral compartment distribution volumes: 20.7 L (8.94%) and 62.4 L (50.80%), respectively; intercompartmental clearance: 4.8 L/h (26.4%). For the PK/PD target of 100% fT(>1xMIC), 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CLCR, but higher doses are needed for MIC = 16 mg/L when CLCR > 100 mL/min. For 100% fT(>4xMIC), the highest dose (24 g/24 h) was not sufficient to ensure adequate exposure, except for MICs of 1 and 4 mg/L. Our model can be used as a support tool for initial dose guidance and during therapeutic drug monitoring.16 p.application/pdfengcc by (c) Martínez Casanova, Javier et al., 2023http://creativecommons.org/licenses/by/3.0/es/Antibiòtics betalactàmicsFarmacocinèticaFarmacovigilànciaBeta lactam antibioticsPharmacokineticsDrug monitoringinfo:eu-repo/semantics/article2023-04-21info:eu-repo/semantics/openAccess36978398