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Steady-State Ceftazidime-Avibactam Serum Concentrations and Dosing Recommendations in a Critically Ill Patient Being Treated for Pseudomonas aeruginosa Pneumonia and Undergoing Continuous Venovenous Hemodiafiltration.

Authors
  • Soukup, Paige1
  • Faust, Andrew C1
  • Edpuganti, Vindhya2, 3
  • Putnam, William C2, 3
  • McKinnell, James A4, 5
  • 1 Department of Pharmacy, Texas Health Presbyterian Hospital of Dallas, Dallas, Texas.
  • 2 Department of Pharmacy Practice, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, Texas.
  • 3 Clinical Pharmacology and Experimental Therapeutics Center, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, Texas.
  • 4 David Geffen School of Medicine, University of California, Los Angeles, California.
  • 5 Infectious Disease Clinical Outcome Research Unit (ID-CORE), Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California.
Type
Published Article
Journal
Pharmacotherapy
Publication Date
Dec 01, 2019
Volume
39
Issue
12
Pages
1216–1222
Identifiers
DOI: 10.1002/phar.2338
PMID: 31596506
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Ceftazidime-avibactam (CAZ-AVI) is a novel intravenous β-lactam/β-lactamase inhibitor combination used in the treatment of multidrug-resistant (MDR) gram-negative infections. Although renal dosing recommendations exist for the medication, limited data are available for dosing in patients receiving continuous renal replacement therapy. In this report, we describe a case in which CAZ-AVI 2.5 g was administered as a 2-hour infusion every 8 hours to a 50-year-old critically ill patient with MDR Pseudomonas aeruginosa (CAZ-AVI minimum inhibitory concentration [MIC] 8 μg/ml) pneumonia who was also receiving continuous venovenous hemodiafiltration (CVVHDF). Total serum concentrations of both ceftazidime and avibactam were measured at ~0.5, 2, 4, and 6 hours after completion of the 2-hour infusion of the 11th dose of CAZ-AVI. Ceftazidime pharmacokinetic parameters were as follows: maximum serum concentration (Cmax ) 152.39 μg/ml, half-life 5.17 hours, volume of distribution at steady state (Vdss ) 11.51 L, clearance 1.54 L/hour, and area under the concentration-time curve (AUC) 1295.38 hour•μg/ml. This regimen achieved free ceftazidime serum concentrations more than 4 times the MIC for 100% of the dosing interval. Avibactam pharmacokinetic parameters were as follows: Cmax 35.83 μg/ml, half-life 5.92 hours, Vdss 12.44 L, clearance 1.45 L/hour, and AUC 343.44 hour•μg/ml, which achieved free avibactam concentrations above 1 μg/ml for 100% of the dosing interval. Higher CAZ-AVI dosing is critical in the treatment of pneumonia due to limited ceftazidime penetration into epithelial lining fluid; however, epithelial lining fluid drug concentrations were not collected or measured. Based on this case report and the available evidence, a dose of CAZ-AVI 2.5 g infused over 2 hours every 8 hours appears to be appropriate for critically ill patients who are being treated for pneumonia and are receiving CVVHDF. © 2019 Pharmacotherapy Publications, Inc.

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