Frequency, Antimicrobial Susceptibility, and Molecular Characterization of Carbapenem-Resistant Enterobacterales Stratified by United States Census Divisions: Results From the INFORM Program (2018–2022)

Abstract

Background. Recently approved β-lactamase inhibitor combinations, such as ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam, have demonstrated a broad spectrum of activity against carbapenem-resistant Enterobacterales (CRE) from US hospitals, but resistance may emerge with the increasing use of these compounds. Aztreonam-avibactam was recently approved in Europe and it is under clinical development in the United States. We evaluated the activity of aztreonam-avibactam and comparators against CREs from US hospitals. Methods. A total of 45 497 Enterobacterales isolates were consecutively collected from 79 US medical centers (36 states) and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed 4 mg/L and a susceptible breakpoint of ≤4 mg/L was applied for comparison. CRE isolates were screened for carbapenemase by whole-genome sequencing. Results. Aztreonam-avibactam inhibited >99.9% of Enterobacterales at ≤4 mg/L. CRE frequencies varied from 0.2% (New England) to 2.4% (Middle Atlantic). Aztreonam-avibactam was active (minimum inhibitory concentration ≤4 mg/L) against 98.6% (408/414) of CREs overall, whereas susceptibility to ceftazidime-avibactam and meropenem-vaborbactam were lowest in the Mountain division (67.7% and 74.2%, respectively) and highest (100.0%) in West North Central. Klebsiella pneumoniae carbapenemase was the most common carbapenemase (65.5% of CREs), followed by New Delhi MBL (10.6%) and oxacillinase-48–like (2.7%). The occurrence of Klebsiella pneumoniae carbapenemase among CREs varied from 14.3% (New England) to 77.8% (East South Central), whereas the frequency of MBLs ranged from ≤3.0% (4 divisions) to 19.4% in Mountain and 42.9% in New England. Conclusions. Aztreonam-avibactam showed potent activity against CRE, including MBL producers. Resistance to ceftazidime-avibactam and meropenem-vaborbactam was observed among CRE because of increasing occurrence of MBL-producing isolates.