(561) In Vitro Activity of Cefiderocol Against Gram-Negative Bacteria Isolated From Burn Patients

Introduction: Cefiderocol (FDC) is a siderophore cephalosporin with activity against Gram-negative (GN) bacteria, including multidrug resistant isolates. Activity of FDC and comparator agents was evaluated against GN bacteria isolated from burn patients.

Methods: GN bacteria were collected from 151 burn patients during 2020-2022 from 26 medical centers in the US and Europe as part of the SENTRY Antimicrobial Surveillance Program. These included 76 Enterobacterales, 40 Pseudomonas aeruginosa, 19 Acinetobacter baumannii-calcoaceticus complex, 13 Stenotrophomonas maltophilia, 2 Acinetobacter courvalinii and 1 Burkholderia cepacia species complex from patients with pneumonia (n=66), skin/soft tissue (n=47), bloodstream (n=22), urinary tract (n=11) or other (n=5) infections. Minimum inhibitory concentrations (MIC) were determined according to CLSI guidelines using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparator agents and iron-depleted CAMHB for FDC. Susceptibility was assessed per CLSI breakpoints. β-lactamase content of P. aeruginosa and Acinetobacter spp. non-susceptible to meropenem and imipenem (Carb-NS) was determined through whole genome sequencing.

Results: All Enterobacterales, P. aeruginosa, and S. maltophilia were susceptible to FDC, as were 95.2% of Acinetobacter spp.. The FDC MIC value against the single B. cepacia species complex was 0.12 mg/L. No Carb-NS Enterobacterales were collected, but 30% of P. aeruginosa and 23.8% of Acinetobacter spp. were Carb-NS. All Carb-NS P. aeruginosa were susceptible to FDC, with only 50-66.7% of the isolates susceptible to newer β-lactam-β-lactamase inhibitor combinations. These isolates carried chromosomal β-lactamase genes, except for two that carried blaVIM-2. FDC was active against 80% of Carb-NS Acinetobacter spp., whereas comparators were active against < 40% of these isolates. These isolates carried acquired blaOXA-23 or blaOXA-72 and the FDC-resistant isolate carried blaPER-1.

Conclusions: FDC had high in vitro activity against contemporary GN isolates collected from burn patients in US and European hospitals, including Carb-NS subsets for which treatment options are limited. These data suggest FDC may be a valuable empiric treatment option for serious infections in burn patients caused by GN pathogens.