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.
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.
Department of Pharmacy, Khoo Teck Puat Hospital, Singapore.
Jessica Hui Fen
JH
Goh
Department of Pharmacy, Khoo Teck Puat Hospital, Singapore.
Siok Ying
SY
Lee
Department of Medicine, Infectious Diseases Division, Khoo Teck Puat Hospital, Singapore.
Say Tat
ST
Ooi
Yong Loo Lin School of Medicine, National University Singapore, Singapore.
Lawrence
L
Lee Soon-U
Yong Loo Lin School of Medicine, National University Singapore, Singapore.
Kim-Hor
KH
Hee
Department of Medicine, Nephrology Division, Khoo Teck Puat Hospital, Singapore.
Claude J
CJ
Renaud
D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002442:Ceftazidime / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*
D000900:Anti-Bacterial Agents; D002442:Ceftazidime
Ceftazidime; MIC; hemodialysis; low flux; pharmacodynamic; pharmacokinetic