In vitro activity of cefiderocol against highly resistant Gram-negative pathogens collected in the SENTRY Surveillance Program between 2020 and 2024.
OBJECTIVES This study investigated the in vitro activity of cefiderocol and comparator antibiotics against Gram-negative bacterial isolates with highly resistant phenotypes collected in the SENTRY Antimicrobial Surveillance Program. METHODS Between 2020 and 2024, consecutive Gram-negative bacterial isolates were collected from hospitalized patients in the USA and Europe, Turkey and Israel. Minimum inhibitory concentrations (MICs) were determined by broth microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Susceptibility was interpreted, as applicable, by CLSI M100 (2026), European Committee on Antimicrobial Susceptibility Testing (EUCAST) (2026), and US Food and Drug Administration (FDA 2026) criteria. RESULTS Cefiderocol was the only antibiotic that inhibited >90% of carbapenem-non-susceptible isolates by CLSI breakpoints (95.5% of 1229 Enterobacterales, 98.8% of 2807 Pseudomonas aeruginosa, 93.7% of 2254 Acinetobacter baumannii-calcoaceticus species complex, and 99.3% of 2341 Stenotrophomonas maltophilia), and susceptibilities to cefiderocol were >90% across various infection sites. Against multidrug-resistant (MDR) Enterobacterales (N=10 606) and P. aeruginosa (N=1817), cefiderocol susceptibility rates were 99.1% and 98.1%, respectively. Susceptibilities to comparator antibiotics ranged between 73.2% (ceftolozane-tazobactam) and 99.8% (aztreonam-avibactam) for MDR Enterobacterales, and between 18.3% (meropenem) and 77.5% (imipenem-relebactam) for MDR P. aeruginosa. 97.4% of 459 DTR P. aeruginosa were susceptible to cefiderocol. Additionally, cefiderocol displayed low MIC50/90 values against Burkholderia cepacia species complex and Achromobacter spp. (0.06/0.5 mg/L and 0.03/0.25 mg/L, respectively). CONCLUSIONS Cefiderocol showed potent in vitro activity against contemporary isolates of Gram-negative bacteria displaying challenging resistance phenotypes.