Pharmacodynamic Target Attainment for Various Ceftazidime Dosing Schemes in High-Flux Hemodialysis

• Type of Material: Article
• Authors: Angela S. Loo, New York-Presbyterian/Weill Cornell Medical Center; Michael Neely, USC Keck School of Medicine; Evan Anderson, Emory University; Cybele Ghossein, Northwestern Memorial Hospital; Milena M. McLaughlin, Northwestern Memorial Hospital; Marc H. Scheetz, Northwestern Memorial Hospital
• Language: English
• Date: 2013-12-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2013, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/AAC.00474-13
• Title of Journal or Parent Work: Antimicrobial Agents and Chemotherapy
• ISSN: 0066-4804
• Volume: 57
• Issue: 12
• Start Page: 5854
• End Page: 5859
• Grant/Funding Information: This study was supported in part by a Midwestern University Chicago College of Pharmacy Faculty Research Stimulation Grant from Midwestern University, Downers Grove, IL.; M. Neely is supported by NIH grants GM068968 and HD070886.
• Keywords: PHARMACOKINETICS; UNITED-STATES; Microbiology; Science & Technology; RESISTANCE; MICROBIOLOGY; AMERICAN MEDICAL-CENTERS; PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL SURVEILLANCE PROGRAM; SIMULATION; IMPAIRED RENAL-FUNCTION; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; INFECTIONS; Life Sciences & Biomedicine; BROAD-SPECTRUM CEPHALOSPORINS
• Research Categories: Health Sciences, Pharmacy; Health Sciences, Medicine and Surgery

Abstract

Ceftazidime is a broad-spectrum cephalosporin with high-level activity against a variety of Gram-negative pathogens, including Pseudomonas aeruginosa. Improved outcomes are associated with cumulative percentages of a 24-h period that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (%T MIC ) of > 45 to 70% of the dosing interval. Optimal dosing to achieve a 90% probability of target attainment (PTA) in patients receiving high-flux hemodialysis (HFHD) is unknown. We used existing data from six anephric adults receiving hemodialysis to construct a population model with the Pmetrics package for R. From the final model's joint probability density, we simulated the PTA for various ceftazidime dosing regimens, HFHD schedules, and organism MICs. For HFHD every 48 h and 1 g of ceftazidime given posthemodialysis, the PTA exceeds 90% for all isolates with MICs of≤8 μg/ml, assuming a goal of 70%T MIC . For 72-h dialysis intervals, postdialysis dosing of 1 g is adequate for achievement of the 70%T MIC goal only for organisms with MICs of≤4 μg/ml, while 2 g is adequate for organisms with MICs of≤8 μg/ml. A dose of 500 mg once daily, regardless of HFHD schedule, has a 90% PTA for organisms with MICs of≤16 μg/ml, while 1 g once daily may achieve 100% PTA even for resistant organisms with a MIC of 32 μg/ml. Therefore, to ensure maximal ceftazidime activity, once-daily dosing of 500 mg to 1 g ceftazidime in patients receiving HFHD may be preferable for critically ill patients when MIC data are unavailable and for more resistant organisms with ceftazidime MICs of 16 to 32 μg/ml.