2112. In vitro Activity of Cefiderocol and Comparator Agents Against Enterobacterales From United States Hospitals Stratified by Infection Type (2020-2022)

BACKGROUND: Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with broad activity against Gram-negative bacteria including multi-drug resistant organisms. The in vitro activity of CFDC and comparator agents was evaluated against Enterobacterales isolates collected during 2020-2022 in the SENTRY Antimicrobial Surveillance Program, stratified by infection type. [Figure: see text] METHODS: 11,805 Enterobacterales from the USA were tested for susceptibility (%S) using CLSI broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) or iron-depleted CAMHB for CFDC. Comparator agents included β-lactam/β-lactamase inhibitor (BL/BLI) combinations ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (I-R) meropenem-vaborbactam (MVB), piperacillin-tazobactam (P/T) as well as meropenem (MEM), cefepime (FEP) and ceftazidime (CAZ). Susceptibility was interpreted according to 2022 CLSI & FDA breakpoints. Carbapenem resistant Enterobacterales (CRE) was defined as resistant to imipenem (IPM) and MEM. Multidrug-resistant (MDR) Enterobacterales was defined as nonsusceptible to at least 1 drug from ≥ 3 classes and extensively drug resistant (XDR) as susceptible to ≤ 2 classes per 2022 CLSI criteria. RESULTS: The most common infection type from which isolates were collected was urinary tract infection (UTI; n=4,136), followed by bloodstream infection (BSI; n=3,256), pneumonia (PNA; n=2,731), intra-abdominal infections (IAI; n=1,015), and skin-soft tissue infections (SSTI; n=667). Among CRE and MDR isolates, CFDC was the most active agent ( > 98%S) for isolates from BSI, PNA, and UTI. Among XDR isolates from BSI and PNA, %S to CFDC ( > 97%) was highest amongst all agents tested. Of the Bl/BLIs, C/T and P/T demonstrated the lowest %S against CRE and MDR isolates from BSI, PNA, UTI and among XDR isolates from BSI and PNA. CONCLUSION: CFDC demonstrated high in vitro activity against Enterobacterales regardless of infection type. Susceptibility for comparator agents was generally lower against isolates with CRE, MDR, and XDR phenotypes. CFDC represents a potential early treatment option for infections caused by Enterobacterales with presumed or defined CRE, MDR, XDR phenotypes, regardless of infection type. DISCLOSURES: Jason J. Bryowsky, PharmD, MS, Shionogi Inc.: Employee Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Joshua Maher, PhD, AbbVie: Grant/Research Support|Affinity Biosensors: Grant/Research Support|AimMax Therapeutics, Inc: Grant/Research Support|Alterity Therapeutics: Grant/Research Support|Amicrobe, Inc: Grant/Research Support|Arietis Pharma: Grant/Research Support|Armata Pharmaceuticals, Inc: Grant/Research Support|Astrellas Pharma, Inc.: Grant/Research Support|Basilea Pharmaceutica AG: Grant/Research Support|Becton Dickinson And Company: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Boost Biomes: Grant/Research Support|Diamond V: Grant/Research Support|Fedora Pharmaceuticals, Inc: Grant/Research Support|Iterum Therapeutics plc: Grant/Research Support|Johnson & Johnson: Grant/Research Support|Kaleido Biosciences, Inc.: Grant/Research Support|Meiji Seika Pharma Co. Ltd.: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer Inc.: Grant/Research Support|Roche Holding AG: Grant/Research Support|Shionogi Inc.: Grant/Research Support|Summmit Therapeutics, Inc.: Grant/Research Support|Zoetis Inc: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Miki Takemura, n/a, Shionogi & Co., Ltd.: Stocks/Bonds Yoshinori Yamano, PhD, Shionogi HQ: Employee