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 (CLCR less than or equal to 10 mL/min, 10 < CLCR less than or equal to 50 mL/min, and CLCR > 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 tazobactum, 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 CLCR < 50 mL/min, t({%})(ss) > MIC90 values were 100% for a panel of 19 pathogens, butin those with CLCR > 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 CLCR > 50 mL/min, in which the risk of under-dosing and clinical failure is important and extra doses are required.