Antimicrobial activity of aztreonam/avibactam and molecular characterization of Enterobacterales not susceptible to ceftazidime/avibactam and/or meropenem/vaborbactam from US medical centres (2016–2024)

BACKGROUND: Resistance to ceftazidime/avibactam and meropenem/vaborbactam has been increasing among carbapenem-resistant Enterobacterales (CRE) in US hospitals recently. We evaluated the activity of aztreonam/avibactam and comparators against isolates that were not susceptible to ceftazidime/avibactam and/or meropenem/vaborbactam and against MBL-producing Enterobacterales. METHODS: A total of 80 927 Enterobacterales isolates were consecutively collected (one per patient) in 2016-2024 from 103 US medical centres and susceptibility tested by broth microdilution in a monitoring laboratory. Among those, 194 (0.24%) were not susceptible to ceftazidime/avibactam or meropenem/vaborbactam, 115 (0.14%) were not susceptible to both ceftazidime/avibactam and meropenem/vaborbactam, and 832 (1.0%) isolates were carbapenem resistant. These isolates were screened for carbapenemase (CBase) genes by WGS. RESULTS: Aztreonam/avibactam was active against 91.9% of ceftazidime/avibactam-non-susceptible isolates (n = 160), 94.0% of meropenem/vaborbactam-non-susceptible isolates (n = 149), 98.1% of CRE and 98.4% of MBL producers (n = 125). Cefiderocol retained activity against 78.8% of ceftazidime/avibactam-non-susceptible isolates, 83.2% of meropenem/vaborbactam-non-susceptible isolates, 94.7% of CRE and 82.1% of MBL producers. A CBase was identified in 159 (82.0%) of isolates not susceptible to ceftazidime/avibactam or meropenem/vaborbactam and in 683 (80.1%) of CREs. NDM (n = 114; 58.8% of isolates) was the most common CBase type among isolates not susceptible to ceftazidime/avibactam or meropenem/vaborbactam. Notably, an MBL was identified in 36.1% (73/202) of CRE collected in 2023-2024. CONCLUSIONS: Aztreonam/avibactam demonstrated potent activity against isolates not susceptible to ceftazidime/avibactam and/or meropenem/vaborbactam as well as against CRE isolates, including MBL producers. The activities of other β-lactamase inhibitor combinations and cefiderocol were adversely affected by the alarming increase of MBL producers in some US hospitals.