Influence of Renal Function on the Pharmacokinetics of Piperacillin/Tazobactam in Intensive Care Unit Patients During Continuous Venovenous Hemofiltration

The pharmacokinetics of piperacillin/tazobactam (4 g/0.5 g every 6 or 8 hours, by 20-minute intravenous infusion) were studied in 14 patients with acute renal failure who underwent continuous venovenous hemofiltration with AN69 membranes. Patients were grouped according to severity (CL(CR) < or =10 mL/min, 10 < CL(CR) < or =50 mL/min, and CL(CR) > 50 mL/min). A noncompartmental analysis was performed. The sieving coefficient (0.78 +/- 0.28) was similar to the unbound fraction (0.65 +/- 0.24) for tazobactam, but it was significantly different (0.34 +/- 0.25) from the unbound fraction (0.78 +/- 0.14) for piperacillin. Extracorporeal clearance was 37.0% +/- 28.8%, 12.7% +/- 12.6%, and 2.8% +/- 3.2% for piperacillin in each group and 62.5% +/- 44.9%, 35.4% +/- 17.0%, and 13.1% +/- 8.0% for tazobactam. No patients presented tazobactam accumulation. In patients with CL(CR) < 50 mL/min, t(%)ss >MIC90 values were 100% for a panel of 19 pathogens, but in those with CL(CR) > 50 mL/min, t(%)ss >MIC90 indexes were 55.5% and 16.6% for pathogens with MIC90 values of 32 and 64. The extracorporeal clearance of piperacillin/tazobactam is clinically significant in patients with CL(CR) > 50 mL/min, in which the risk of underdosing and clinical failure is important and extra doses are required.