Can Piperacillin Dose Be Predicted by Renal Function in Intensive Care Unit Patients? Comparison of 3 Different...

Although the increased risk of piperacillin underexposure has been previously evidenced in intensive care unit patients with augmented renal clearance, it is still unclear whether the piperacillin dose could be a priori adapted according to renal function in these patients.

Steady-state concentrations (Css) of piperacillin were retrospectively collected from 159 adult intensive care unit patients who received a continuous infusion of piperacillin. Renal function was estimated for each patient using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration 2021 formulas. The association between these formulas and the risk of piperacillin underexposure and overexposure (Css <80 and >157 mg/L, respectively) was investigated using receiver operating characteristic curves. The proportion of patients with piperacillin underexposure or overexposure to a 16 g/d regimen and the theoretical daily dose (DPDth) required to obtain a Css of 80 mg/L were calculated for 4 different creatinine clearance groups: 60-90, 90-130, 130-160, and >160 mL/min.

Creatinine clearance calculated using the Cockcroft-Gault equation was a slightly better predictor of piperacillin underexposure and overexposure, with cutoff values of 128 and 81 mL/min, respectively. The percentage of patients with underexposure increased from 23% to 88% from the 60 to 90 to the ≥160 mL/min group, whereas the mean DPDth simultaneously increased from 13.9 to 30.8 g/d but with an important interindividual variability.

These results support a progressive increase in the daily dose of piperacillin with respect to renal function; however, the important interindividual variability precluded the determination of a robust dosing recommendation, making therapeutic drug monitoring mandatory.