A systematic review and meta-analysis found resistance to cefiderocol was low overall but “alarmingly high” among certain types of carbapenem-resistant bacteria, Greek researchers reported late last week in Clinical Microbiology and Infection.
Sold under the brand name Fetroja, cefiderocol is a cephalosporin antibiotic with a novel method of penetrating the tough outer membrane of gram-negative bacteria, including multidrug-resistant pathogens. Approved for the treatment of complicated urinary tract infections by the US Food and Drug Administration (FDA) in 2019 and for the treatment of nosocomial pneumonia in 2020, cefiderocol is considered a last-resort option for carbapenem-resistant bacterial infections.
Higher resistance in certain carbapenem-resistant isolates
With resistance to cefiderocol being increasingly reported, researchers from the University of Crete set out to estimate the global cefiderocol non-susceptibility (CFDC-NS) in clinical isolates of the gram-negative pathogens considered to be among the most serious antimicrobial resistance threats: Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. The 78 studies they reviewed included 82,035 clinical isolates from Europe (50%), the Americas (33%), and the Western Pacific Region (17%).
CFDC-NS was low overall but varied by species, with a rate of 8.8% for A baumannii, 3% for Enterobacterales, 1.4% for P aeruginosa, and 0.4% for S maltophilia. And while cefiderocol appeared to retain relatively good activity against carbapenem-resistant bacteria overall, CFDC-NS was much higher in carbapenem-resistant A baumannii (13.2%) and carbapenem-resistant Enterobacterales (12.4%) and significantly higher in New Delhi metallo-beta-lactamase (NDM)–producing A baumannii (44.7%), NDM–producing Enterobacterales, and cefatazidime/avibactam-resistant Enterobacterales (36.6%).
Among other limitations, the study authors note that CFDC-NS varied by breakpoint definition, with the FDA, Clinical Laboratory Standards Institute (CLSI), and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) all having different susceptibility thresholds.
“Antimicrobial stewardship, infection control and continued surveillance at the local level, as well as regular updating and reporting of global CFDC-NS estimates, are imperative for preventing or delaying emerging resistance against cefiderocol,” they wrote. “Harmonization of EUCAST and CLSI breakpoints would help such efforts.”