Steady-State Ceftazidime-Avibactam Serum Concentrations and Dosing Recommendations in a Critically Ill Patient Being Treated for Pseudomonas aeruginosa Pneumonia and Undergoing Continuous Venovenous Hemodiafiltration

Abstract

Ceftazidime-avibactam (CAZ-AVI) is a novel intravenous β-lactam/β-lactamase inhibitor combination used in the treatment of multidrug-resistant (MDR) gram-negative infections. Although renal dosing recommendations exist for the medication, limited data are available for dosing in patients receiving continuous renal replacement therapy. In this report, we describe a case in which CAZ-AVI 2.5 g was administered as a 2-hour infusion every 8 hours to a 50-year-old critically ill patient with MDR Pseudomonas aeruginosa (CAZ-AVI minimum inhibitory concentration [MIC] 8 μg/ml) pneumonia who was also receiving continuous venovenous hemodiafiltration (CVVHDF). Total serum concentrations of both ceftazidime and avibactam were measured at ~0.5, 2, 4, and 6 hours after completion of the 2-hour infusion of the 11th dose of CAZ-AVI. Ceftazidime pharmacokinetic parameters were as follows: maximum serum concentration (C_max ) 152.39 μg/ml, half-life 5.17 hours, volume of distribution at steady state (Vd_ss ) 11.51 L, clearance 1.54 L/hour, and area under the concentration-time curve (AUC) 1295.38 hour•μg/ml. This regimen achieved free ceftazidime serum concentrations more than 4 times the MIC for 100% of the dosing interval. Avibactam pharmacokinetic parameters were as follows: C_max 35.83 μg/ml, half-life 5.92 hours, Vd_ss 12.44 L, clearance 1.45 L/hour, and AUC 343.44 hour•μg/ml, which achieved free avibactam concentrations above 1 μg/ml for 100% of the dosing interval. Higher CAZ-AVI dosing is critical in the treatment of pneumonia due to limited ceftazidime penetration into epithelial lining fluid; however, epithelial lining fluid drug concentrations were not collected or measured. Based on this case report and the available evidence, a dose of CAZ-AVI 2.5 g infused over 2 hours every 8 hours appears to be appropriate for critically ill patients who are being treated for pneumonia and are receiving CVVHDF.

Keywords: avibactam; ceftazidime; continuous renal replacement therapy; pharmacokinetics.