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

BACKGROUND: The use of regional citrate anticoagulation during continuous veno-venous haemodiafiltration (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 (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.