(473) Comparative Activity of Cefiderocol on Bloodstream Infection Isolates From U.S. ICU Patients

Introduction: Cefiderocol (CFDC) is a siderophore cephalosporin with broad activity against Gram-negative bacteria, including multi-drug resistant isolates. The activity of CFDC and comparator agents was evaluated against isolates causing bloodstream infection (BSI) in patients hospitalized in intensive care units (ICU) from participating US hospitals.

Methods: A total of 832 BSI isolates were collected from 37 US medical centers ICUs and included in the SENTRY Antimicrobial Surveillance Program (2020 to 2022). 664 Enterobacterales (ENT), 115 P. aeruginosa, 33 Acinetobacter baumannii-calcoaceticus complex (ABC) and 20 S. maltophilia were tested for susceptibility (S). Minimum inhibitory concentrations were determined according to CLSI guidelines using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparator agents and iron-depleted CAMHB for CFDC. Susceptibility was assessed per CLSI and FDA breakpoints. Carbapenem-non-susceptible (Carb-NS) was defined as non-susceptible to meropenem and imipenem.

Results: 0.9% of ENT, 15.7% of P. aeruginosa, 45.5% of ABC, and 100% of S. maltophilia tested as Carb-NS. Among new β-lactamase inhibitor combinations (BLICs), ceftolozane/tazobactam displayed the lowest S (94.4%) for ENT; however, against Carb-NS ENT, CFDC and ceftazidime/avibactam showed 100% S, while S for meropenem/vaborbactam and imipenem/relebactam was 83.3%. P. aeruginosa S to CFDC and BLICs were >94%. However, against Carb-NS P. aeruginosa CFDC was the most potent agent (MIC50/90 0.12/2 mg/L) with 100%/88.9% S per CLSI/FDA breakpoints, respectively. CFDC %S for ABC was the highest and 90.9%/87.9% S among comparator agents per CLSI/FDA, while S for meropenem was 54.5% and 48.5% for ampicillin/sulbactam (SAM). CFDC (MIC50/90, 0.25/8 mg/L) displayed better in vitro potency against Carb-NS ABC compared to SAM (MIC50/90, 32/>64 mg/L). Among S. maltophilia, CFDC was 100 %S per CLSI breakpoint and the most potent agent with MIC50/90, 0.06/0.12 mg/L.

Conclusions: CFDC was highly active against contemporary BSI isolates of ENT, P. aeruginosa, ABC, and S. maltophilia, including Carb-NS subsets for which treatment options are limited. These data suggest CFDC may be a valuable empiric treatment option for serious Gram-negative infections in patients admitted to the ICU with BSI.