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Bhatnagar, Amelia; Bumpus-White, Porscha; Sabour, Sarah; Bodnar, Janine; Burks, Albert; Chen, Arlene; Craft, Bradley; Jacobsen, Christine; Karlsson, Maria; Marmerow, Michael; Lonsway, David; Neff, Lindsay; Maruca, Tyler; Nazarian, Elizabeth; Perry, Zachary; Rossi, Alessandro; Vagnone, Paula S; Tran, Michael; Valley, Ann M; Brown, Allison C

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

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  • Media type: E-Article
  • Title: 2747. Aztreonam-Avibactam Susceptibility Testing Program for Metallo-β-Lactamase-Producing Enterobacterales collected through the Antimicrobial Resistance Laboratory Network, March 2019 to April 2023
  • Contributor: Bhatnagar, Amelia; Bumpus-White, Porscha; Sabour, Sarah; Bodnar, Janine; Burks, Albert; Chen, Arlene; Craft, Bradley; Jacobsen, Christine; Karlsson, Maria; Marmerow, Michael; Lonsway, David; Neff, Lindsay; Maruca, Tyler; Nazarian, Elizabeth; Perry, Zachary; Rossi, Alessandro; Vagnone, Paula S; Tran, Michael; Valley, Ann M; Brown, Allison C
  • Published: Oxford University Press (OUP), 2023
  • Published in: Open Forum Infectious Diseases, 10 (2023) Supplement_2
  • Language: English
  • DOI: 10.1093/ofid/ofad500.2358
  • ISSN: 2328-8957
  • Keywords: Infectious Diseases ; Oncology
  • Origination:
  • Footnote:
  • Description: Abstract 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., blaNDM, blaVIM, or blaIMP), 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 blaNDM, 24 blaNDM/blaOXA-48-like, 14 blaKPC/blaNDM, 2 blaIMP, 2 blaKPC/blaIMP, and 2 blaNDM/blaIMP. 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 MIC50 and MIC90 of AZA were 0.5/4 µg/mL and 8/4 µg/mL, respectively; the MIC50 and MIC90 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
  • Access State: Open Access