Antibiotic Candidate Cefiderocol Demonstrates Activity Against Drug-Resistant Pathogens

Siderophore cephalosporin is superior to colistin

Results from the first global surveillance study of cefiderocol (Shionogi Inc.), an investigational siderophore cephalosporin, have been presented at IDWeek 2016 in New Orleans, Louisiana. Cefiderocol showed activity against gram-negative pathogens, including carbapenem-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii, as well as carbapenem-resistant Enterobacteriaceae. The results were presented using in vitro data from 8,765 test strains of P. aeruginosa, A. baumannii, and Enterobacteriaceae isolated in 2014 and 2015 from patients in North America and Europe.

The study evaluated the in vitro activity of cefiderocol in comparison with various marketed gram-negative treatments, including colistin and the newer agents ceftazidime/avibactam and ceftolozane/tazobactam. Key findings from the study included:

  • Cefiderocol showed the lowest MIC50 and MIC90 values (the minimal inhibitory concentration required to inhibit the growth of 50% and 90% of organisms, respectively) of all compounds tested.
  • The growth of 99.6% of all isolates was inhibited at 4 mcg/mL of cefiderocol.
  • Cefiderocol was active against many of the gram-negative pathogens that were not susceptible to other antibiotics. (A total of 1,290 isolates [14.7%] were nonsusceptible to meropenem.)

Cefiderocol is a siderophore cephalosporin that can penetrate into gram-negative pathogens. It binds to free iron and is actively transported into bacterial cells through the outer membrane. This “Trojan horse” strategy allows cefiderocol to enter the space between the bacterial cell walls and disrupt cell-wall synthesis. In addition, cefiderocol is stable against nearly all beta-lactamases, including both the serine and metallo-carbapenemases. 

Cefiderocol has been designated by the FDA as a qualified infectious disease product, which allows a priority review and provides eligibility for fast-track approval status. Registrational studies are ongoing in patients with complicated urinary tract infections and in patients with carbapenem-resistant pathogens. 

Source: Shionogi; October 26, 2016.