The in vitro activity of aztreonam-avibactam and cefiderocol against globally collected clinical metallo-β-lactamase- and/or serine-carbapenemase-positive Enterobacterales isolates and the utility of commonly used in vitro diagnostic kits.

The NG-test CARBA 5 and Xpert Carba-R IVD kits were tested against 269 clinical Enterobacterales isolates selected for their previously determined carbapenemase content from the ATLAS Global Surveillance program, primarily from 2020 to 2022. Antimicrobial susceptibility testing by broth microdilution was performed for aztreonam-avibactam, cefiderocol, and othe agents using EUCAST 2025 breakpoints for interpretation. The CARBA 5 and Carba-R IVD kits accurately identified all NDM (93), KPC (36), and OXA-48-like (43) carbapenemases. The CARBA 5 detected all IMP (42) and 45/47 VIM, and the Carba-R detected all VIM (47) and 21/42 IMP. Aztreonam-avibactam was active against carbapenemase-producing isolates (percent susceptible [carbapenemases]): 90.7% (NDM), 92.9% (NDM+OXA-48-like), 100% (IMP, VIM, and KPC), and 88.9% (OXA-48-like). Cefiderocol susceptibility was as follows: 38.7% (NDM), 50.0% (NDM+OXA-48-like), 77.5% (IMP), 82.5% (VIM), 75.9% (KPC), and 100% (OXA-48-like). The most common carbapenemases in Enterobacterales include NDM, KPC, and OXA-48-like enzymes, all of which were accurately identified by the CARBA 5 and Carba-R kits. Aztreonam-avibactam demonstrated potent in vitro activity against isolates determined to be positive for carbapenemases by these kits, offering a potential therapeutic option when one of these isolates is encountered in the clinic.IMPORTANCEIn vitro diagnostic (IVD) kits exist that detect carbapenemases in clinical isolates of Enterobacterales. Their utility is hampered by the limited options to reliably treat infections caused by Enterobacterales that produce metallo-β-lactamases. Here, we test the utility of IVD kits for detecting carbapenemases in a recent collection of clinical Enterobacterales isolates and determine the in vitro activity of aztreonam-avibactam, cefiderocol, and other comparator agents against isolates that were positive for carbapenemases.