Clearance of Piperacillin-Tazobactam and Vancomycin During Continuous Renal Replacement With Regional Citrate Anticoagulation.

ABSTRACT

BACKGROUND: The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation. METHODS: This study measured piperacillin-tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS: Seventeen sampling intervals in 15 patients (9 receiving piperacillin-tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR) 32.2-38.6], 70 mL/min (IQR 62.7-76.2) for tazobactam, and 29.5 mL/min (IQR 26.2-32) for vancomycin. CONCLUSIONS: This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin-tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.