2762. Activity of Cefiderocol and Comparator Agents Against Difficult to Treat Resistance (DTR) Gram-negative Isolates, Collected During 2020-2022 as Part of SENTRY Antimicrobial Surveillance Program
Authors: DeJonge Boudewijn L , Nguyen Sean T , Bryowsky Jason J , Longshaw Christopher M , Maher Joshua , Mendes Rodrigo E , Takemura Miki , Yamano Yoshinori 
Published: November 2023

Abstract

Background
Difficult to Treat Resistant (DTR) Gram-negative isolates show treatment-limiting resistance to all first-line agents; β-lactams and fluoroquinolones. Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with a unique mode of entry into bacteria, showing good activity against Gram-negative bacteria. Here, susceptibility of CFDC and comparator agents was determined against DTR isolates of Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus species complex (ABC).
Activity of Cefiderocol and Comparator Agents Against Difficult to Treat Resistance (DTR) Gram-negative Isolates

Methods
Minimum inhibitory concentrations were determined according to CLSI guidelines against 24,084 Enterobacterales, 7,310 P. aeruginosa, and 2,479 ABC isolates, collected in 2020–2022 in Europe and the USA as part of the SENTRY program, using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparator agents and iron-depleted CAMHB for CFDC. Susceptibility was assessed according to CLSI, EUCAST and FDA breakpoints (BPs). DTR was defined as being non-susceptible, using CLSI BPs, to fluoroquinolones and β-lactams, except for CFDC and β-lactam/β-lactamase inhibitor (BL/BLI) combinations.

Results
1.6% (n=387) of the Enterobacterales isolates showed the DTR phenotype, the majority being K. pneumoniae (n=332; 85.8%). The isolates showed high susceptibility to CFDC (95.3% and 81.1% using CLSI/FDA or EUCAST BPs, respectively). Comparator agents, including novel BL/BLI combinations, showed susceptibility of &lt; 80%, except for tigecycline (94.1%, FDA BPs). For P. aeruginosa 4.1% (n=299) showed the DTR phenotype, of which 98.3%, 97.7%, and 89.6% were susceptible to CFDC, according to CLSI, EUCAST and FDA BPs respectively. Colistin was also active (99.7% susceptible, EUCAST BPs) whereas other agents, including novel BL/BLI combinations, had susceptibility of &lt; 65%. Amongst ABC, 47.1% (n=1167) showed the DTR phenotype, and 96.2%, 93.8%, and 89% were susceptible to CFDC according to CLSI, EUCAST and FDA BPs, respectively. Susceptibility to comparator agents was &lt; 40%, except for colistin (81.2%, EUCAST BPs).

Conclusion
DTR isolates remained susceptible to CFDC, indicative of a low degree of cross resistance with β-lactams, including BL/BLI combinations, and fluoroquinolones.

Disclosures
Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Jason J. Bryowsky, PharmD, MS, Shionogi Inc.: Employee Christopher M. Longshaw, PhD, Shionogi BV: 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