Helio S. Sader, Rodrigo E. Mendes, John H. Kimbrough, Marisa Winkler, Mariana Castanheira
BACKGROUND: Infections caused by multidrug-resistant (MDR) bacteria have increased drastically in the last two decades. We evaluated the activities of newer β-lactamase inhibitor combinations (BLICs) against a large collection of contemporary MDR Enterobacterales from United States medical centres. METHODS: A total of 42,306 clinical isolates (1/patient) were consecutively collected from 82 US medical centres in 2020-2024 and susceptibility tested at a monitoring laboratory by broth microdilution against 19 antimicrobial agents, including aztreonam-avibactam, ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam. Cefiderocol was only tested against carbapenem-resistant Enterobacterales (CRE). MDR was defined as nonsusceptibility to ≥3 classes and extensively drug-resistant (XDR) as susceptibility to ≤2 classes. Results for 8,635 MDR, 208 XDR, and 451 CRE isolates were analysed. CRE isolates were screened for carbapenemases by whole genome sequencing. RESULTS: MDR, XDR, and CRE phenotypes were observed in 20.4%, 0.5%, and 1.1% of isolates, respectively. The most active agents against MDR isolates were aztreonam-avibactam (99.7% susceptible), meropenem-vaborbactam (98.5% susceptible), and ceftazidime-avibactam (98.4% susceptible). Only aztreonam-avibactam (97.6% susceptible) and tigecycline (88.5% susceptible) retained good activity against XDR isolates. The most active agents against CRE (per CLSI/US FDA) were aztreonam-avibactam (97.1% susceptible), tigecycline (95.8% susceptible), and cefiderocol (94.0% susceptible). The most common carbapenemases identified among CREs were KPC (51.4% of CREs), NDM (23.1%), and OXA-48 type (4.4%). The newer BLICs and cefiderocol were highly active against KPC producers, but only aztreonam-avibactam and cefiderocol exhibited good activity against MBL producers. CONCLUSIONS: Aztreonam-avibactam exhibited potent activity against MDR, XDR, and CRE isolates, including those not susceptible to other BLICs and/or cefiderocol.