(551) Antimicrobial Susceptibility of Multidrug-Resistant Enterobacterales to Recently Approved β-Lactams

Introduction: To evaluate the in vitro activity of aztreonam-avibactam (ATM-AVI) and other recently approved β-lactams against multidrug-resistant (MDR), extensively-drug resistant (XDR), and carbapenem-resistant Enterobacterales (CRE) isolated from patients in US hospitals.

Methods: Clinical isolates (1/patient) were consecutively collected from 82 US medical centers in 2019-2023 and tested for susceptibility at a monitoring laboratory by broth microdilution against ATM-AVI, ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), cefiderocol (FDR), and comparators. MDR was defined as non-susceptible (S) to ≥3 classes and XDR as S to ≤2 classes. Results for 8416 MDR, 199 XDR, and 392 CRE isolates were analyzed. FDR was only tested against CRE (all years) and cephalosporin-resistant MDR (CephR-MDR) isolates from 2023. CRE isolates were screened for carbapenemases by whole genome sequencing.

Results: The frequencies of MDR, XDR, and CRE were higher among isolates from intensive care units (ICU) patients (24.6%, 0.8%, and 1.9%, respectively) compared to non-ICU patients (17.4%, 0.3%, and 0.6%, respectively). ATM-AVI inhibited 99.8% of MDR, 98.5% of XDR, and 98.5% of CRE isolates at ≤4 mg/L (EUCAST S breakpoint). CAZ-AVI and MEM-VAB were active against 98.9% of MDR but showed limited activity against XDR (72.4%S and 64.1%S, respectively) and CRE (81.1%S and 77.8%S, respectively). IMI-REL was slightly less active than CAZ-AVI and MEM-VAB against these 3 resistant subsets. FDR was active against 95.3% of CRE. The most active compounds against CephR-MDR (n=510) were ATM-AVI (99.2%S) and FDR (97.4%S); CAZ-AVI, MEM-VAB, and IMI-REL were active against 94.1% of CephR-MDR isolates. ATM-AVI retained activity against 91.4% of CAZ-AVI-R (n=93), 96.6% of MEM-VAB-non-S (n=87), 99.9% of IMI-REL-non-S (n=1,371), and 87.1% of FDR-non-S (n=31) isolates. Among metallo-β-lactamase producers (n=71; 18.1% of CREs), 98.6% were ATM-AVI-S and 83.1% were FDR-S.

Conclusions: ATM-AVI exhibited potent in vitro activity and spectrum against Enterobacterales from ICU and non-ICU patients, including MDR, XDR, CRE and isolates non-S to CAZ-AVI, MEM-VAB, IMI-REL, and/or FDR. In general, lower S rates were observed among ICU compared with non-ICU isolates.