Pharmacodynamic modeling of checkerboard data obtained with β-lactam- β-lactamases inhibitor combination: aztreonam-avibactam - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2017

Pharmacodynamic modeling of checkerboard data obtained with β-lactam- β-lactamases inhibitor combination: aztreonam-avibactam

Résumé

Background: The aim of this study was to develop a new modeling approach to quantify the in vitro activity of aztreonam-avibactam (ATM-AVI) combination against multi-drug resistant (MDR) Enterobacteriaceae with diverse β-lactamases profiles. Methods: MIC checkerboard assays were performed with 11 Enterobacteriaceae isolates (4 Klebsiella pneumoniae, 1 Escherichia coli, 2 Citrobacter freundii, 3 Enterobacter cloacae, and 1 Enterobacter aerogenes). All isolates produced a metallo β-lactamase and additional other β-lactamases, resulting in elevated MIC values for ATM. ATM MICs (MICATM) in the absence and in the presence of AVI at different concentrations (ranging from 0.0625 to 4 mg/L) were determined according to CLSI guidelines. MICATM versus AVI concentrations were fitted by an inhibitory Emax effect model with a baseline effect parameter. Results: A concentration-dependent relationship was observed with a rapid initial reduction of MICATM at low AVI concentrations and reaching a maximum at AVI concentration ≥ 4 mg/L, that was adequately fitted by Equation 1. AVI efficacy was characterized by MICATM,base/MICATM,0 ratios ranging between 89 and 10207. AVI potency was characterized by very low IC50 values (between 0.00022 and 0.053 mg/L). MIC values determined when AVI concentration was equal to 4 mg/L were close to MICATM,base estimated by the model. Conclusions: An inhibitory Emax model with a baseline effect was shown to describe adequately these ATM-AVI checkerboard data and was able to characterize AVI efficacy (MICATM,base/MICATM,0) and potency (IC50).
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hal-02512124 , version 1 (19-03-2020)

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  • HAL Id : hal-02512124 , version 1

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Alexia Chauzy. Pharmacodynamic modeling of checkerboard data obtained with β-lactam- β-lactamases inhibitor combination: aztreonam-avibactam. ISAP/EPASG Scientific Meeting, Apr 2017, Vienne, Austria. ⟨hal-02512124⟩
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