Pharmacokinetics of extended-infusion piperacillin-tazobactam in critically ill patients undergoing continuous renal replacement therapy.

Study ObjectiveTo evaluate the pharmacokinetic and pharmacodynamic profiles of piperacillin-tazobactam administered as a 4-hour infusion in critically ill patients undergoing continuous renal replacement therapy (CRRT). DesignProspective, observational, pharmacokinetic study. SettingIntensive care unit of a tertiary care hospital in Montreal, Canada. PatientsTwenty critically ill adults who were undergoing continuous venovenous hemodiafiltration and receiving a 4-hour infusion of piperacillin 4g-tazobactam 0.5g every 8hours for a documented or suspected infection. InterventionBlood samples were collected every hour over an 8-hour dosing interval. Prefilter and postfilter blood samples, and effluent and urine samples were also collected. Measurements and Main ResultsThe primary outcome was the proportion of patients who achievedan unbound piperacillin plasma concentration above a target minimum inhibitory concentration (MIC) of 64mg/L (MIC that inhibits 90% of isolates for Pseudomonas aeruginosa) for at least 50% of the dosing interval; 18 (90%) of the 20 patients achieved this outcome. In all patients, the free piperacillin concentrations were above the Pseudomonas aeruginosa breakpoint of 16mg/L for the entire time interval. Regarding piperacillin pharmacokinetic parameters, the median (interquartile range) minimum unbound plasma concentration was 65.15mg/L (51.30-89.30), maximum unbound plasma concentration was 141.3mg/L (116.75-173.90), sieving coefficient was 0.809 (0.738-0.938), total clearance was 65.82ml/minute (53.79-102.87), and renal clearance was 0.16ml/minute (0.05-3.04). The median CRRT dose was 32.0ml/kg/h (25.0-39.8). ConclusionsAdministration of a 4-hour infusion of piperacillin-tazobactam was associated with a favorable pharmacodynamic profile in patients undergoing CRRT. Concentrations associated with maximal activity were attained in our patients.