1. Ceftazidime/avibactam serum concentration in patients on ECMO.
- Author
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Curtiaud A, Petit M, Chommeloux J, Pineton de Chambrun M, Hekimian G, Schmidt M, Combes A, and Luyt CE
- Subjects
- Humans, Male, Female, Retrospective Studies, Middle Aged, Adult, Aged, Pseudomonas aeruginosa drug effects, Microbial Sensitivity Tests, Enterobacteriaceae drug effects, Ceftazidime pharmacokinetics, Ceftazidime administration & dosage, Ceftazidime therapeutic use, Ceftazidime blood, Azabicyclo Compounds pharmacokinetics, Azabicyclo Compounds administration & dosage, Azabicyclo Compounds therapeutic use, Azabicyclo Compounds blood, Drug Combinations, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents blood, Extracorporeal Membrane Oxygenation
- Abstract
Objectives: The use of extracorporeal membrane oxygenation (ECMO) may alter blood levels of several drugs, including antibiotics, leading to under dosing of these drugs and thus to potential treatment failure. No data exist on pharmacokinetics of new antimicrobial, in particular ceftazidime/avibactam. We therefore perform this study to evaluate ceftazidime/avibactam blood levels in ECMO patients and find factors associated with underdosing., Methods: Retrospective observational study of patients on ECMO having received ceftazidime/avibactam and in whom trough blood levels of ceftazidime and avibactam were available. Main outcome measurement was the number of patients with ceftazidime and avibactam blood levels above predefined cut-off values, derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa, namely 8 mg/L for ceftazidime and 4 mg/L for avibactam, and explored factors associated with underdosing., Results: Twenty-three ceftazidime/avibactam trough levels were available in 14 ECMO patients, all of them having received veno-venous ECMO for SARS-CoV-2-associated pneumonia. Although ceftazidime levels were above 8 mg/L in all except one patient, nine (39%) of the avibactam dosages were below 4 mg/L. Increased renal clearance (creatinine clearance > 130 mL/min) was the main factor associated with under dosing, since 7 out of the 10 dosages below the predefined cut-offs were measured in patients with this condition., Conclusions: In ECMO patients receiving ceftazidime/avibactam, ceftazidime and avibactam serum levels are above EUCAST breakpoints in most cases, justifying the use of normal dosing in ECMO patients. Increased renal clearance may lead to ceftazidime and avibactam under dosing., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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