What question did this study set out to answer?

To evaluate the in vitro efficacy of aztreonam/avibactam against Enterobacterales from patients with HAP, VAP, and cIAIs.

June 12, 2026Open Access

In vitro activity of aztreonam/avibactam and comparators against Enterobacterales isolates from patients with hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated intra-abdominal infections (ATLAS, 2021–2022)

Key Points

To evaluate the in vitro efficacy of aztreonam/avibactam against Enterobacterales from patients with HAP, VAP, and cIAIs.
Tested 14,564 Enterobacterales isolates using broth microdilution per CLSI guidelines.
Conducted molecular characterization on CRE isolates and additional analysis on MBL-positive strains, including cefiderocol.
Screened MBL-positive E. coli for PBP3 mutations using whole-genome sequencing.
Aztreonam/avibactam was 99.5% susceptible to all Enterobacterales with MIC90 of 0.25 mg/L.
Among 577 MBL-positive isolates, susceptibility of aztreonam/avibactam was 95.1%, compared to cefiderocol (50.3%), colistin (73.8%), and tigecycline (95.0%).
E. coli with PBP3 mutations showed only 31.4% susceptibility (MIC ≤4 mg/L).

Abstract

BACKGROUND: Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) and complicated intra-abdominal infections (cIAIs) caused by carbapenem-resistant Enterobacterales (CRE) are associated with high mortality. Metallo-β-lactamase (MBL)-producing strains represent therapeutic challenge compromising β-lactams and limiting treatment options. Aztreonam/avibactam is a novel combination designed to overcome MBL-mediated resistance. OBJECTIVES: To evaluate in vitro activity of aztreonam/avibactam and comparators against Enterobacterales from patients with HAP, VAP or cIAI collected globally (Africa/Middle East, Asia-Pacific, Europe and Latin America) during 2021-22 ATLAS surveillance program focusing on MBL-positive strains. METHODS: 14 564 Enterobacterales isolates were tested by broth microdilution per CLSI guidelines. CRE isolates underwent molecular characterization and MBL-positive isolates underwent additional molecular and susceptibility analysis, including cefiderocol. MBL-positive Escherichia coli isolates were screened for PBP3 mutations by whole-genome sequencing. MICs were interpreted using EUCAST breakpoints as appropriate. RESULTS: Aztreonam/avibactam was 99.5% susceptible (MIC ≤4 mg/L) for all Enterobacterales (MIC90 0.25 mg/L) and maintained high susceptibility against MDR (98.9%), ESBL (99.0%) and CRE (96.4%). Among 577 MBL-positive isolates (88% NDM), aztreonam/avibactam was 95.1% susceptible, compared with cefiderocol (50.3%), colistin (73.8%) and tigecycline (95.0%). Activity was consistent across regions and carbapenemase genotypes, including co-producers of multiple β-lactamases. However, E. coli isolates harbouring PBP3 insertions (YRIK/YRIN) and plasmid-mediated AmpC β-lactamases (n = 35) were 31.4% susceptible (MIC ≤4 mg/L). CONCLUSIONS: Aztreonam/avibactam demonstrated potent and consistent in vitro activity against Enterobacterales causing serious hospital infections, including MBL-producing CRE. These findings underscore aztreonam/avibactam's therapeutic potential and the need for rapid diagnostics and global surveillance to guide regional stewardship and treatment strategies for MDR infections.

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