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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
Author(s) -
Goh Jessica Hui Fen,
Lee Siok Ying,
Ooi Say Tat,
Lee SoonU Lawrence,
Hee KimHor,
Renaud Claude J.
Publication year - 2016
Publication title -
hemodialysis international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.658
H-Index - 47
eISSN - 1542-4758
pISSN - 1492-7535
DOI - 10.1111/hdi.12377
Subject(s) - medicine , hemodialysis , ceftazidime , tolerability , dialysis , dosing , pharmacodynamics , end stage renal disease , avibactam , pharmacokinetics , adverse effect , pharmacology , gastroenterology , surgery , biology , bacteria , pseudomonas aeruginosa , genetics
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.

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