2112. In vitro Activity of Cefiderocol and Comparator Agents Against Enterobacterales From United States Hospitals Stratified by Infection Type (2020-2022)
Authors: Bryowsky Jason J , DeJonge Boudewijn L , Nguyen Sean T , Maher Joshua , Mendes Rodrigo E , Takemura Miki , Yamano Yoshinori 
Published: November 2023

Abstract

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.

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 ( &gt; 98%S) for isolates from BSI, PNA, and UTI. Among XDR isolates from BSI and PNA, %S to CFDC ( &gt; 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