Aztreonam-avibactam Demonstrates Potent Activity Against Carbapenem-resistant Enterobacterales Collected From US Medical Centers Over a 6-year Period (2017-2022)

Background: Carbapenem-resistant Enterobacterales (CREs) are a major public health threat because treatment options are limited. The predominant resistance mechanism in CREs is the production of carbapenemases. Aztreonam-avibactam was shown to possess activity against CREs with class A, B, and D carbapenemases. Herein, the activity of aztreonam-avibactam and comparators were evaluated against Enterobacterales collected between 2017 and 2022 in the United States.

Methods: Antimicrobial susceptibility testing for aztreonam-avibactam, ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefiderocol, tigecycline, and colistin was conducted using the reference broth microdilution method. Isolates resistant to imipenem or meropenem were defined as carbapenem-resistant, underwent whole-genome Sequencing, and were analyzed for the presence of carbapenemase genes.

Results: Of the 54 576 Enterobacterales, 0.9% were CREs and only 3.7% of the CREs were susceptible to aztreonam; the addition of avibactam increased susceptibility to 98.4% based on EUCAST breakpoints. Cefiderocol and tigecycline were the next most potent agents, inhibiting 94.7% of the CREs at current breakpoints. Whole-genome Sequencing analysis of the CREs revealed that 82.6% carried a carbapenemase with 360 isolates having only a class A carbapenemase. KPC-encoding genes were the predominant carbapenemase genes identified with 50.4% found in CREs from New York, New Jersey, and Pennsylvania. Aztreonam-avibactam was highly active against CREs carrying class A, B, and/or D carbapenemases with susceptibility rates of 99.4%, 98.0%, and 100%, respectively. Moreover, 94.4% of isolates with no carbapenemases detected were susceptible to aztreonam-avibactam.

Conclusions: Aztreonam-avibactam demonstrates potent activity toward CREs with different carbapenem-resistance mechanisms. The combination is an anticipated welcome addition to the clinician's toolbox giving physicians another option to treat CREs.

antimicrobial resistance; avibactam; aztreonam; carbapenem-resistant Enterobacterales; β-lactam-β-lactamase-inhibitor combinations.