Abstract
Background: Carbapenemase-producing-Enterobacterales (CPE) infections are on the rise and associated with increased morbidity and mortality, due to a limited number of therapeutic options. The goal of this study was to assess the synergistic activity of ceftazidime-avibactam (CZA) and aztreonam (ATM) combination against phenotypically and genetically characterized blaMBL-producing Enterobacterales.Methods: In this study, forty (n=40) non-repeat, CPE clinical isolates, including: n=35 Klebsiella pneumoniae, n=2 each of Escherichia coli and Klebsiella oxytoca, and n=1 Enterobacter cloacae isolates were identified and susceptibilities were assessed using the Vitek-II compact (bioMérieux, Inc., France) and Microscan Walkaway (Beckman Coulter) systems. Genotypic analysis of clinically relevant carbapenemases was performed by using Xpert-Carba-R assay on GeneXpert (Cepheid, USA). The minimum inhibitory concentrations (MICs) and synergy testing of CZA and ATM, were tested by the Etest fixed ratio method (bioMérieux, Inc., France). The fractional inhibitory concentration index (FICI) was calculated for each antibiotic.Results: Our results showed that 97.5% of blaMBL-producing Enterobacterales isolates were susceptible to an in-vitro CZA + ATM combination regimen. The fractional inhibitory concentration index (FICI) ranged from 0.001 to 1.001. Among the tested CPE isolates, Synergy was observed in 36/40 (90%), an additive effect was observed in 5% (n=2)’ while two (5%) isolates showed indifference. There was no antagonism observed in our study.Conclusion: Our study exhibited a potent activity of CZA and ATM combination synergy against clinical CPE metallo- β-lactamase producers. More extensive studies involving a variety of Gram-negative pathogens with different resistance mechanisms are required to determine the efficacy of this combination regimen.Keywords: Synergy; Aztreonam; Ceftazidime-Avibactam; Carbapenem-Resistant Enterobacterales; Etest
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