In Vitro Activities of Aztreonam-avibactam and Comparator Agents against Metallo-β-lactamase-producing Enterobacterales Collected in the Middle East and Africa, ATLAS Global Surveillance Program, 2018-2022
Year: 2025
Type: article
Abstract: Background: Aztreonam-avibactam is a β-lactam/β-lactamase inhibitor combination being developed for use against carbapenem-resistant Enterobacterales (CRE), particularly those carrying metallo-β-lactamases (MBLs). The in vitro activity of aztreonam-avibactam against MBL-positive Enterobacterales collected in 2016-2022 in Middle East/Africa region as a part of the ATLAS Global surveillance program was evaluated. Methods: 9,828 non-duplicate Enterobacterales were collected from 23 sites in 11 countries. Antimicrobial susceptibility testing was by broth microdilution according to CLSI guidelines. Avibactam was fixed at a concentration of 4 mg/L. Isolates with meropenem MIC >1 mg/L were screened for β-lactamase genes by PCR. Results: Genes encoding an MBL (IMP, VIM and/or NDM) were identified in 459 isolates (321 Klebsiella pneumoniae, 44 Enterobacter spp., 35 Escherichia coli, and 59 isolates of 11 other species). Among MBL-positive isolates, 444/459 (96.7%) carried NDM, while cohorts carried VIM (n=14; 3.0%) or IMP (n=2; 0.4%). One isolate that carried VIM also carried NDM. Against all isolates collected in the Middle East/Africa, the aztreonam-avibactam MIC₉₀ value was 0.12 µg/mL while the aztreonam MIC₉₀ was >64 µg/mL. The aztreonam-avibactam MIC₉₀ value against MBL-positive isolates was 0.5 µg/mL while the MIC₉₀ value for aztreonam alone was >64 µg/mL. All but one MBL-producing isolate (99.8%) tested with aztreonam-avibactam MIC values ≤8 µg/mL, the proposed PK/PD breakpoint for this agent. Conclusion: MIC₉₀ values demonstrated potent in vitro activity of aztreonam-avibactam against isolates of Enterobacterales carrying MBLs. The widespread dissemination of MBLs among increasingly difficult-to-treat organisms underscores the importance of new agents such as aztreonam-avibactam that retain activity against these pathogens.
Authors: Dr Mark Estabrook, Dr Gregory Stone, Dr Daniel Sahm
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,900
OpenAlex ID: W4408046841