Predictive Factors of Piperacillin Exposure and the Impact on Target Attainment after Continuous Infusion Administration to Critically Ill Patients

• Published in: Antibiotics (Basel) Vol. 12; no. 3; p. 531
• Main Authors: Martínez-Casanova, Javier, Esteve-Pitarch, Erika, Colom-Codina, Helena, Gumucio-Sanguino, Víctor Daniel, Cobo-Sacristán, Sara, Shaw, Evelyn, Maisterra-Santos, Kristel, Sabater-Riera, Joan, Pérez-Fernandez, Xosé L, Rigo-Bonnin, Raül, Tubau-Quintano, Fe, Carratalà, Jordi, Padullés-Zamora, Ariadna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2023; MDPI
• Subjects: Antibiotics; beta-lactam antibiotic; Chronic kidney failure; Complications and side effects; Confidence intervals; continuous infusion; Creatinine; creatinine clearance; Critically ill; Demographic aspects; Dosage; Dosage and administration; Drug dosages; Drug therapy; Empirical analysis; Minimum inhibitory concentration; Parameter estimation; Patients; Pharmacodynamics; Pharmacokinetics; Pharmacology; Piperacillin; Plasma; population pharmacokinetic approach; Renal function; Risk factors; Sepsis; Standard error; Tazobactam; Therapeutic drug monitoring; Spain; population pharmacokinetic approach; continuous infusion; beta-lactam antibiotic; creatinine clearance; piperacillin; critically ill; therapeutic drug monitoring
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12030531

Critically 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 (CL
) 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%
T
, 12 g of piperacillin provide a probability of target attainment > 90% for MIC < 16 mg/L, regardless of CL
, but higher doses are needed for MIC = 16 mg/L when CL
> 100 mL/min. For 100%
T
, 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.