Abstract
Background
Cefiderocol (CFDC) is a siderophore cephalosporin with broad activity against Gram-negative bacteria including multi-drug resistant isolates. The in vitro activity of CFDC and comparator agents was evaluated against pediatric (0-17 years old) isolates collected in 2020–2022 as part of the SENTRY Antimicrobial Surveillance Program.
In vitro Activity of Cefiderocol and Comparator Agents Against Pediatric Isolates
Methods
2,249 Enterobacterales (ENT), 707 P. aeruginosa, 194 Acinetobacter baumannii-calcoaceticus complex (ABC) and 220 S. maltophilia from the USA and Europe were tested for susceptibility (%S) by broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB). Iron-depleted CAMHB was applied for CFDC. Comparators included newer β-lactam/β-lactamase inhibitor (BL/BLI) combinations ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (I-R) and meropenem-vaborbactam (MVB) as well as ampicillin/sulbactam (SAM) meropenem (MEM) and colistin (CST). %S was interpreted according to 2023 CLSI & EUCAST breakpoints. Carbapenem non-susceptible (CarbNS) was defined as non-susceptibility to imipenem and MEM.
Results
All agents displayed >96 %S for ENT while CFDC (MIC50/90, 2/4 mg/L; 91.7 %S) was the most active agent against CarbNS ENT. P. aeruginosa susceptibilities to CFDC and BL/BLI combinations were >97.0%. CFDC was the most potent agent against CarbNS P. aeruginosa with MIC50/90 values of 0.12/0.25 mg/L and 100 %S & 98.5 %S per CLSI & EUCAST breakpoints, respectively. ABC susceptibility to CFDC was >97% per CLSI & EUCAST while the susceptibility for MEM was 87.1% (CLSI & EUCAST) and SAM was 80.9% (CLSI). CFDC (MIC50/90, 0.25/1 mg/L; 95.7 %S) displayed better in vitro potency in CarbNS ABC as compared to SAM (MIC50/90, 32/ >64 mg/L; 17.4 %S CLSI) and CST (MIC50/90, 0.5/ >8 mg/L; 78.3%S EUCAST). Among pediatric S. maltophilia, CFDC was the most active agent with MIC50/90, 0.06/0.25 and 100 %S per CLSI & EUCAST breakpoints.
Conclusion
CFDC was a highly active β-lactam against contemporary pediatric isolates of Enterobacterales, P. aeruginosa, ABC, and S. maltophilia, including CarbNS subsets for which treatment options are limited. These data suggest CFDC may be a valuable treatment for serious Gram-negative infections in pediatric patients.
Disclosures
Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Jason J. Bryowsky, PharmD, MS, Shionogi Inc.: Employee Anne Henriksen, PhD, Shionogi: 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