Renal function and its impact on the concentration of ceftazidime-avibactam: A cross-sectional study.

Autor: Lanini S; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy. Electronic address: simone.lanini@uniud.it., Giuliano S; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy., Angelini J; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy., Ferin S; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy., Martini L; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy., Baraldo M; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy., Cossettini S; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy., Roberts J; University of Queensland Centre for Clinical Research, Faculty of Medicine The University of Queensland, Brisbane, Australia; Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia; Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France., Tascini C; Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy; University of Udine Department of Medicine (DMED) via Colugna, Udine, Italy.
Jazyk: angličtina
Zdroj: International journal of antimicrobial agents [Int J Antimicrob Agents] 2024 Dec; Vol. 64 (6), pp. 107351. Date of Electronic Publication: 2024 Oct 01.
DOI: 10.1016/j.ijantimicag.2024.107351
Abstrakt: Objective: This study measured the effect of renal function on the plasma concentrations of ceftazidime and avibactam in critically ill patients. We also sought to measure the concentration ratio of ceftazidime to avibactam.
Methods: This was a cohort study at a tertiary referral centre in Italy, on patients treated with continuous infusion of ceftazidime-avibactam (CAZ-AVI) between November 2019 and December 2023. The association between creatine clearance (CrCl) and free plasma ceftazidime and avibactam concentration, as well as CAZ-AVI ratio was explored to assess correlation and potential risk to fail to achieve target therapeutic concentration.
Results: Fifty-two patients, predominantly male (75%), with a median age of 68.5 y were included. Our analyses provided strong evidence for inverse correlation between CrCl and both free-CAZ (r = -0.627; R 2 = 0.3936; P < 0.001) and free-AVI plasma concentration (r = -0.619; R 2 = 0.3832; P < 0.001). Overall CrCl alone could explain about 40% of overall variation of either free-CAZ and free-AVI. Linear models suggest that free-CAZ and free-AVI concentration drop of about 7.31% and 9.23% for each 10 point increase of CrCl, respectively. Assessment of the CAZ-AVI ratio supports a direct linear association with CrCl suggesting that free-AVI concentration is more affected by CrCl variation than free-CAZ concentration. Patients with CrCl ≥130 mL/min showed a significantly higher risk of suboptimal drug exposure (i.e., less than 4 times the MIC) both to CAZ and AVI.
Conclusion: The findings emphasise the need for individualised dosing strategies of CAZ-AVI based on renal function, for antibiotics used in critically ill patients. The study suggests that underdosing in patients with high CrCl is likely to be common and as such could affect drug effectiveness.
(Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
Databáze: MEDLINE
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