MIC profiling of ceftazidime/avibactam against two carbapenemase-producing Klebsiella pneumoniae isolates.

Autor: Zidaru A; Department of Pharmacy, Baylor St Luke's Medical Center, Houston, TX 77030, USA; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA., Eales BM; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA., Wang W; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA., Merlau PR; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA., Lasco TM; Department of Pathology, Baylor St Luke's Medical Center, Houston, TX 77030, USA., Sofjan AK; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA., Tam VH; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA. Electronic address: vtam@uh.edu.
Jazyk: angličtina
Zdroj: Journal of global antimicrobial resistance [J Glob Antimicrob Resist] 2020 Dec; Vol. 23, pp. 385-387. Date of Electronic Publication: 2020 Nov 06.
DOI: 10.1016/j.jgar.2020.10.014
Abstrakt: Objectives: The aim of this study was to correlate the results of a modified susceptibility testing method with outcomes of ceftazidime/avibactam (CAZ/AVI) therapy.
Methods: Two bloodstream K. pneumoniae isolates (CAZ/AVI-susceptible) from an abdominal source were recovered from two unrelated patients. Both patients were treated with CAZ/AVI but had discordant outcomes: KP118 (eradication within 24 h) and KP286 (persistent bacteraemia for over 30 days). Carbapenemase production in the two isolates was confirmed by Carba NP test. The CAZ minimum inhibitory concentration (MIC) was determined with escalating AVI concentrations (0-16 mg/L). The concentration-response was characterised by the sigmoid inhibitory maximum effect model. The best-fit parameter values were used to predict %T > MICi associated with CAZ/AVI exposures expected in peritoneal fluid after standard dosing (2.5 g every 8 h). These CAZ/AVI exposures were simulated in a hollow-fibre infection model (HFIM), and the bacterial responses were correlated with observed clinical outcomes.
Results: The AVI-dependent reduction in CAZ MIC was well characterised in both bacterial isolates (r 2  ≥ 0.98). In the HFIM, sustained suppression of KP118 (T > MICi = 100%) was observed over 5 days, but not with KP286 (T > MICi < 100%). These observations are consistent with the clinical course of the patients.
Conclusions: The discordant patient outcomes could be potentially explained by MIC profiling of CAZ/AVI. This method appears to be more robust than conventional susceptibility testing in predicting positive clinical outcome of CAZ/AVI therapy, and the clinical utility of this approach should be further investigated.
Competing Interests: Declaration of Competing Interest The authors report no declarations of interest.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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