Pharmacokinetics of Ceftazidime-Avibactam in a Critical Intracerebral Hemorrhage Patient Receiving Intermittent Venovenous Hemodiafiltration

Abstract Background: The aim of this study was to investigate the appropriate dose of ceftazidime-avibactam (CAZ-AVI) for critically ill patients receiving intermittent venovenous hemodiafiltration (VVHDF). Methods: CAZ-AVI administered at 1.875 g every 24 h by intravenous injection was used to treat multidrug-resistant Klebsiella pneumoniae in a critically ill patient receiving 6h VVHDF every other day. On dialysis day, VVHDF began at 12h after the previous dosing. Plasma drug concentrations of ceftazidime and avibactam were measured at 0, 2, 4, 6, 9, 12, 15, 18 and 24 h after the third dosage of CAZ-AVI administration. A pharmacokinetic analysis was performed using PK Solover 2.0. Results: The pharmacokinetic parameters of ceftazidime on dialysis and non-dialysis day, respectively, were as follow: maximum plasma concentration (Cmax) 102.02 and 93.49 mg/L, minimum plasma concentration (Cmin) 28.41 and 45.73 mg/L, plasma concentration at 12h (C12h) 74.17 and 60.07 mg/L, elimination half-life (t1/2) 13.09 and 26.45 h, area under the concentration-time curve (AUC) 1511.98 and 1507.36 mg·h/L, clearance (CL) 0.98 and 0.46 L/h, apparent volume of distribution at the steady state (Vss) 16.94 and 17.25 L. The pharmacokinetic parameters of avibactam on dialysis and non-dialysis day, respectively, were as follow: Cmax 16.88 and 13.35 mg/L, Cmin 4.62 and 6.99 mg/L, C12h 10.58 and 9.18 mg/L, t1/2 14.63 and 22.09 h, AUC 229.47 and 216.46 mg·h/L, CL 1.15 and 0.85 L/h, Vss 22.04 and 27.89 L. The plasma concentrations of ceftazidime and avibactam remained above the minimum inhibitory concentration (MIC) during the 24h dosing interval.Conclusions: Based on this report, a dose of CAZ-AVI 1.875g every 24h appears to be appropriate for critically ill patients receiving intermittent VVHDF. This is the first study of CAZ-AVI pharmacokinetics with intermittent VVHDF. That is, the dosage of CAZ-AVI should not be changed between dialysis and non-dialysis day when patient received VVHDF every other day, VVHDF was conducted 12h after CAZ-AVI administration, and no supplemental dose should be administered after VVHDF session. Further data that include multiple patients and dialysis modes are needed to verify the optimal CAZ-AVI dosing strategy in critically ill patients requiring intermittent VVHDF.