Post-hemodialysis dosing of 1 vs. 2 g of ceftazidime in anuric end-stage renal disease patients on low-flux dialysis and its pharmacodynamic implications on clinical use.

Abstract

Ceftazidime is a cost-effective antimicrobial against Gram-negative pathogens associated with sepsis in end-stage renal disease (ESRD) hemodialysis patients with potential for wider use with the advent of ceftazidime-avibactam. Dosing ceftazidime post-hemodialysis appears attractive and convenient, but limited in vivo data on pharmacodynamic efficacy (PE) attainment, defined as >70% of the interdialytic period drug concentrations exceed susceptible pathogens minimal inhibitory concentrations (MICs) (%TMIC), warrants further assessment. We therefore evaluated PE and tolerability of 1 against 2 g regime in anuric ESRD patients on low-flux hemodialysis. Two doses of 1 or 2 g ceftazidime were administered post-hemodialysis prior to 48- and 72-hour interdialytic intervals in ESRD inpatients without active infections. Peak and trough concentrations (mg/L) were assayed using a validated liquid chromatography-tandem mass spectrometry method. Proportion of patients achieving PE for known pathogens with MICs ≤ 8 mg/L and adverse effects were assessed. Six (43%) and eight (57%) adult patients received 1 and 2 g dose, respectively. Median (25th-75th percentile), peak, 48- and 72-hour trough ceftazidime concentrations were 78 (60-98) vs. 158 (128-196), 37 (23-37) vs. 49 (39-71), and 13 (12-20) vs. 26 (21-41) mg/L, respectively, resulting in 100% TMIC for both doses. One patient on the 1-g dose experienced mild pruritus. Reliable and safe PE attainment over both 48- and 72-hour interdialytic interval was achievable with 1 g of ceftazidime dosed post-hemodialysis. The 2 g dose was equally effective and well tolerated but may not be necessary. These findings need validation in non-anuric patients, high-flux hemodialysis, and during avibactam co-administration.