Evaluation of imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam and cefepime-zidebactam activities on a wide collection of French clinical Enterobacterales isolates

Abstract

In recent years, novel β-lactam-inhibitor combinations (imipenem-relebactam (I/R), meropenem-vaborbactam (M/V), aztreonam-avibactam (A/A)) have been commercialized and some are not yet on the market (cefepime-zidebactam (C/Z)). The objective of this study was to evaluate the efficacy of these β-lactam-β-lactamase inhibitors (BL/BLIs) combinations against a wide collection of French clinical multiresistant Enterobacterales isolates and to assess the performance of the E-test MIC method for I/R and M/V. BL/BLIs MICs were determined by broth microdilution on a collection of 200 ESBL-producing and 414 carbapenem-resistant clinical Enterobacterales (K. pneumoniae (271), E. coli (245), E. cloacae complex (48), other species (50)) including 292 carbapenemase-producing isolates. E-test method was evaluated for the determination of I/R and M/V MICs using 131 isolates from this collection. All the combinations were active against most ESBL-producing isolates (99-100 %), but C/Z and A/A MIC90 were lower than that of I/R and M/V (2mg/L and 2mg/L versus 8mg/L and 8mg/L). The M/V and I/R E-tests performances were close to those required by the FDA recommendations: Categorical agreement (CA) and Essential agreement (EA) ≥ 90 %, Major discrepancy (MD) and Very major discrepancy (VMD) < 3 %): 96.9 % (CA), 92.4 % (EA), 1.2 % (MD), 6.1 % (VMD) for I/R and 94.7 % (CA), 96.9 % (EA), 4.1 % (MD), 8.8 % (VMD) for M/V. This work confirmed the interest of C/Z and A/A combinations against carbapenem-resistant Enterobacterales isolates compared with M/V and I/R. Additionally, the findings indicate that the E-test method can be used for the determination of M/V and I/R MIC for E. coli and K. pneumoniae strains.

Keywords: Aztreonam-avibactam; Carbapenemase; Cefepime-zidebactam; E-test; ESBL; Enterobacterales; Imipenem-relebactam; MIC; Meropenem-vaborbactam; resistance.