Characterization of and Species Complex Isolates with Decreased Susceptibility to Cephalosporins from United States Hospitals and Activity of Aztreonam-Avibactam and Comparator Agents (2019-2023).

BACKGROUND

(CFC) and (ECLC) species complexes represent important causes of hospital-associated infections, frequently are related to outbreaks, and have a great ability to develop antimicrobial resistance. We evaluated a large collection of CFC and ECLC isolates with decreased susceptibility to broad-spectrum cephalosporins (Ceph-DS) from United States (US) hospitals.

METHODS

A total of 43,325 Enterobacterales (1/patient) were collected in 2019-2023 and susceptibility tested by broth microdilution; among those, 5106 (11.8%) were CFC ( = 1374) or ECLC ( = 3732). Ceph-DS CFC ( = 379) and ECLC isolates ( = 1065), defined as isolates with ceftazidime MICs ≥ 16 mg/L and/or cefepime MICs ≥ 2 mg/L, were screened for β-lactamase genes by whole genome sequencing.

RESULTS

The most common ESBLs were CTX-M type ( = 98; 47.6% of ESBL producers), SHV type ( = 94; 45.6%), and OXA type ( = 78; 37.9%); ≥2 ESBLs were identified in 65 isolates (31.6%), mainly OXA-1/30 plus a CTX-M. A carbapenemase was identified in 55 of 64 (85.9%) carbapenem-resistant (CB-R) isolates, including KPC type (40 isolates; 62.5% of CB-R) and NDM-1 (16; 23.4% of CB-R). Aztreonam-avibactam was active against 99.6% of Ceph-DS and 100.0% of ESBL producers and CB-R isolates, including NDM producers. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of ESBL producers (excluding carbapenemase co-producers) and 70.3-71.9% of CB-R isolates. Cefiderocol was active against 82.8% of CB-R isolates but only 46.7% of MBL producers.

CONCLUSIONS

Aztreonam-avibactam was highly active against cephalosporin-nonsusceptible ECLC and CFC, including MBL producers. The activities of ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were compromised against CB-R isolates due to the high frequency of NDM producers.