Multidrug-resistant Enterobacterales in United States hospitals: Frequency and susceptibility to newer β-lactamase inhibitor combinations (2020-2024).

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.