ABSTRACT Carbapenem-resistant Enterobacterales (CRE) present a major global health concern due to rapid spread, high mortality, and limited treatment options. Metallo-β-lactamase (MBL)-producing CRE, particularly those harboring New Delhi metallo-β-lactamase (NDM) variants and co-expressing other beta-lactamases, are a significant therapeutic challenge as they exhibit resistance to most β-lactam/β-lactamase inhibitor combinations. This study evaluated the in vitro activity of aztreonam-avibactam (ATM-AVI) and comparators against Enterobacterales bloodstream isolates ( N = 10,376) collected between 2021 and 2022 across Africa and the Middle East, Asia-Pacific, Europe, and Latin America, as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) Global Surveillance Program. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, with susceptibility interpreted using 2025 European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, as appropriate. ATM-AVI demonstrated robust activity, inhibiting 99.8% of Enterobacterales at a concentration of ≤4 mg/L (EUCAST susceptibility breakpoint) and maintaining activity across resistance phenotypes, including 99.6% of multi-drug resistant (MDR), 98.9% of CRE, and 99.9% of extended-spectrum beta-lactamases (ESBL) screen-positive isolates. Among MBL-positive CRE isolates, 97.0% were susceptible to ATM-AVI at the EUCAST breakpoint (≤4 mg/L), compared with 52.7% susceptible to cefiderocol at its EUCAST breakpoint (≤2 mg/L). ATM-AVI remained robust against MBL-positive isolates co-carrying ESBLs (97.8%) and other carbapenemases, like Klebsiella pneumoniae carbapenemase (KPC) (100%) and oxacillinase-48 (OXA-48)/OXA-48-like enzymes (98.2%). Among MBL-positive isolates co-carrying AmpC-type β-lactamases, 78.7% were susceptible to ATM-AVI at the EUCAST breakpoint. ATM-AVI demonstrated potent activity against Enterobacterales , including MDR, CRE, and MBL-positive phenotypes, across regions. Its ability to overcome resistance mediated by multiple β-lactamases highlights clinical potential for managing severe infections like bloodstream infections (BSIs), and the need for global surveillance data to drive clinical decision-making and regional stewardship programs. IMPORTANCE Carbapenem-resistant Enterobacterales (CRE) are a serious global health threat due to their rapid spread and limited treatment options. This study highlights the promising potential of aztreonam-avibactam (ATM-AVI) as a powerful treatment against these resistant bacteria. ATM-AVI was tested on a large number of bacterial samples from various regions worldwide and showed strong effectiveness, even against strains that are resistant to most other treatments. This is particularly important for managing severe infections, such as bloodstream infections, which can be life-threatening. The study underscores the need for ongoing global surveillance to guide treatment decisions and improve health outcomes. Patients suffering from infections caused by resistant bacteria, as well as healthcare providers, could greatly benefit from the findings of this research, as it offers hope for more effective treatment options.
Rossolini et al. (2026) studied this question.