2747. Aztreonam-Avibactam Susceptibility Testing Program for Metallo-β-Lactamase-Producing Enterobacterales collected through the Antimicrobial Resistance Laboratory Network, March 2019 to April 2023

BACKGROUND: Metallo-β-lactamase-producing Enterobacterales (MBL-E) are a major public health concern as they cause infections with few effective treatment options. Aztreonam-avibactam (AZA) is a β-lactam/β-lactamase inhibitor combination agent in the drug development pipeline that is active against MBL-E. Though clinical studies are ongoing, the effective components can be administered by combining two FDA-approved drugs: aztreonam and ceftazidime-avibactam. In 2019, CDC initiated a program in the Antimicrobial Resistance Laboratory Network (AR Lab Network), the Expanded Antimicrobial Susceptibility Testing Program for Hard-to-Treat Infections, to provide antimicrobial susceptibility testing (AST) of MBL-E for AZA. We provide a summary of the program’s results. METHODS: Seven AR Lab Network laboratories validated the use of a digital dispenser to create custom broth microdilution panels for AZA AST. Testing requests must be for clinical decision-making purposes. Isolates must be an Enterobacterales and have laboratory results positive for an MBL gene (i.e., bla(NDM), bla(VIM), or bla(IMP)), or be not susceptible to all β-lactams tested. AZA testing results for confirmed MBL-E were reported back to submitters within 3 working days from receipt of the isolate and shared with CDC. RESULTS: From March 2019 through April 2023, AZA AST was performed for 250 isolates: 103 Escherichia coli, 86 Klebsiella pneumoniae, 46 Enterobacter cloacae complex, 8 K. oxytoca, 2 Providencia rettgeri, 1 K. aerogenes, 1 Morganella morganii, 1 Proteus mirabilis, 1 E. hormaechei, and 1 Citrobacter amalonaticus. Carbapenemase genes detected were: 206 bla(NDM), 24 bla(NDM)/bla(OXA-48-like), 14 bla(KPC)/bla(NDM), 2 bla(IMP), 2 bla(KPC)/bla(IMP), and 2 bla(NDM)/bla(IMP). All isolates were resistant to ceftazidime-avibactam; 227/250 (90.8%) were not susceptible to aztreonam (≥8 µg/mL). For isolates not susceptible to aztreonam, the addition of avibactam resulted in a median 128-fold MIC reduction of aztreonam. The MIC range of AZA was ≤0.03/4 - >64/4 µg/mL. Overall, the MIC(50) and MIC(90) of AZA were 0.5/4 µg/mL and 8/4 µg/mL, respectively; the MIC(50) and MIC(90) for E. coli were higher than other species, 4/4 µg/mL and 16/4 µg/mL. CONCLUSION: Our data suggest that AZA has potent in vitro activity against MBL-E collected in the United States. DISCLOSURES: All Authors: No reported disclosures