Abstract
Cefiderocol is a siderophore-conjugated cephalosporin with broad activity against Gram-negative (GN) bacteria, including carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. Cefiderocol was approved by the FDA for treatment of complicated urinary tract infection, hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia and by the European Medicines Agency (EMA) for aerobic GN infections in adults with few treatment options. In this study, we analyzed the susceptibility of cefiderocol against GN clinical isolates that were collected from hospitalized patients in the United States and Europe in 2020 as part of the SENTRY Antimicrobial Surveillance Program. GN isolates, including 8,047 Enterobacterales, 2,282 P. aeruginosa, 650 Acinetobacter species, and 338 S. maltophilia isolates, were consecutively collected from patients in 66 hospitals in 19 countries. Susceptibility testing was performed using the CLSI broth microdilution method, and cefiderocol was tested in iron-depleted cation-adjusted Mueller-Hinton broth. Cefiderocol activity against resistant isolates, including CRE and extensively drug-resistant (XDR) isolates, was determined. Enterobacterales susceptibility to cefiderocol was 99.8% (CLSI), and CRE susceptibility was 98.2%. Cefiderocol was the most active antimicrobial against all P. aeruginosa isolates with MIC(50/90) values of 0.12/0.5 mg/L, respectively (99.6% susceptible). A total of 256 P. aeruginosa isolates were XDR, 97.3% were susceptible to cefiderocol, and 7.4% were susceptible to meropenem. Acinetobacter susceptibility to cefiderocol was 97.7%. S. maltophilia susceptibility to cefiderocol was 100.0% (CLSI, 2021) and 97.9% (CLSI, 2022). These in vitro data suggest that cefiderocol is an important therapeutic option for the treatment of infections caused by Gram-negative pathogens, including isolates resistant to carbapenems with few therapeutic options. IMPORTANCE Cefiderocol is the first siderophore-conjugated cephalosporin approved for use in the treatment of human bacterial infections. Cefiderocol has broad-spectrum Gram-negative activity against difficult-to-treat bacterial pathogens that can cause serious infections. Our study examines the activity of cefiderocol against a large global collection of Gram-negative clinical isolates collected from hospitalized patients in 2020. In addition, we compare the activities of cefiderocol and recently approved β-lactam-β-lactamase inhibitor combinations against various antimicrobial-resistant pathogen groups including carbapenem-resistant Enterobacterales, meropenem-resistant Pseudomonas aeruginosa, and meropenem-resistant Acinetobacter spp. as well as isolates resistant to most classes of antimicrobial drugs. Cefiderocol was the most active antimicrobial tested against the isolates in this study. Our in vitro data suggest that cefiderocol may be useful for treatment of serious infections caused by drug-resistant Gram-negative organisms for patients with limited treatment options.