Pharmacokinetics and Dialytic Clearance of Ceftazidime-Avibactam in a Critically Ill Patient on Continuous Venovenous Hemofiltration

Abstract

Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were as follows: maximum plasma concentration (C_max), 61.10 and 14.54 mg/liter; minimum plasma concentration (C_min), 31.96 and 8.45 mg/liter; half-life (t_1/2), 6.07 and 6.78 h; apparent volume of distribution at the steady state (V_ss), 27.23 and 30.81 liters; total clearance at the steady state (CL_ss), 2.87 and 2.95 liters/h; area under the concentration-time curve from 0 to 8 h (AUC_0-8), 347.87 and 85.69 mg · h/liter. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%, respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for avibactam was 1.59 liters/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data that include multiple patients and dialysis modes are needed to verify the optimal ceftazidime-avibactam dosing strategy during critical illness and CVVH.

Keywords: avibactam; ceftazidime; dialysis; hemofiltration; pharmacokinetics; renal replacement.

FIG 1

Prefiltration concentration-time profiles of ceftazidime (solid line, filled circles) and avibactam (dotted line, open circles) in plasma before and after the fourth dose of ceftazidime-avibactam (1.25 g) in relation to the MIC of the infecting P. aeruginosa pathogen (dashed horizontal line). The shaded region represents the infusion period, accounting for overfill volume and residual fluid volume in the tubing. Data in the y axis are in the log scale.