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

From the Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain (A. Arzuaga, Dr Gascón, A. Isla, Dr Pedraz); Intensive Care Unit, Santiago Apóstol Hospital, Vitoria-Gasteiz, Spain (Dr Maynar, Dr Corral, Dr Fonesca); Intensive Care Unit, Doce de Octubre Hospital, Madrid, Spain (Dr Sánchez-Izquierdo); Intensive Care Unit, Joan XXIII University Hospital, University Rovira & Virgili, Tarragona, Spain (Dr Rello); and Microbiology Unit, Santiago Apóstol Hospital, Vitoria-Gasteiz, Spain (Dr Canut).

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 10 mL/min, 10 < CL_CR 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.

Key Words: continuous venovenous hemofiltration (CVVH) • appropriate antimicrobial therapy • piperacillin • tazobactam • pharmacokinetics • peritonitis • sepsis

Address for reprints: Dr J. L. Pedraz, Laboratorio de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Paseo de la Universidad no. 7, 01006 Vitoria-Gasteiz, Spain.

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