Activity of aztreonam-avibactam against Enterobacterales resistant to recently approved beta-lactamase inhibitor combinations collected in Europe, Latin America, and the Asia-Pacific Region (2020–2022)

Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs). We evaluated a large collection of CRE isolates, including those nonsusceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam. Overall, 24,580 Enterobacterales isolates were consecutively collected (1/patient) in 2020–2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC). Of those, 1,016 (4.1%) were CRE. Isolates were susceptibility tested by broth microdilution. CRE isolates were screened for carbapenemase genes by whole genome sequencing. Aztreonam-avibactam inhibited 99.6% of CREs. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam were active against 64.6%, 57.4%, and 50.7% of CRE isolates, respectively; most of the nonsusceptible isolates carried metallo-beta-lactamases. Aztreonam-avibactam was active against ≥98.9% of isolates nonsusceptible to these BLICs. The activity of these BLICs varied by region, with highest susceptibility rates observed in W-EU (76.9% for ceftazidime-avibactam, 72.5% for meropenem-vaborbactam, 63.8% for imipenem-relebactam) and the lowest susceptibility rates identified in the APAC region (39.9% for ceftazidime-avibactam, 37.8% for meropenem-vaborbactam, and 27.5% for imipenem-relebactam). The most common carbapenemase types overall were KPC (44.6% of CREs), NDM (29.9%), and OXA-48–like (16.0%). KPC predominated in LATAM (64.1% of CREs in the region) and W-EU (61.1%). MBL occurrence was highest in APAC (59.5% of CREs in the region), followed by LATAM (34.0%), E-EU (28.9%), and W-EU (23.6%). In summary, Aztreonam-avibactam demonstrated potent activity against CRE isolates resistant to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam independent of the carbapenemase produced.