Vol.73 No.S-1 April 2025
Phase II clinical trial of cefiderocol in patients with complicated urinary tract infection caused by Gram-negative uropathogens and phase III trial in patients with Gram-negative nosocomial pneumonia
1)Iguchi Nephrourology and Internal Medicine Clinic Shinkoiwa, Medical Town Shinkoiwa 5, 6, 7F, 1-49-10 Shinkoiwa, Katsushika-ku, Tokyo, Japan
2)Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine
3)Department of Infectious Diseases, School of Medicine, International University of Health and Welfare
Abstract
Cefiderocol (CFDC) is a novel siderophore cephalosporin antibiotic that has been with demonstrated to exert activity against a broad range of Gram-negative bacteria. In the international phase II APEKS-cUTI trial, which was conducted in patients with complicated urinary tract infections (cUTIs), the composite endpoint achievement rate of clinical and microbiological outcomes after 7 days of treatment was 72.6% in the CFDC group and 54.6% in the imipenem/cilastatin (IPM/CS) group. The adjusted between-group difference was 18.6% (95% confidence interval: 8.2-28.9%). As the lower limit exceeded the non-inferiority margin of -20%, non-inferiority to IPM/CS was established, and furthermore, CFDC demonstrated superiority as the lower limit exceeded 0.
In the international phase III APEKS-NP trial, which included patients with nosocomial pneumonia, the 14-day all-cause mortality rate was 12.4% in the CFDC group and 11.6% in the high-dose extended infusion of meropenem (MEPM) group. The adjusted between-group difference was 0.8% (95% confidence interval: -6.6-8.2%). As the lower limit did not exceed the non-inferiority margin of -12.5%, non-inferiority to MEPM was established for CFDC. Tolerability was also comparable between the two groups. Post-hoc analyses of both trials suggested that CFDC is effective against OXA-48-type carbapenemase-producing bacteria and metallo-β-lactamase-producing bacteria. Furthermore, CFDC treatment was shown not to affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Based on the results of both trials, CFDC is expected to become a promising choice for the treatment of cUTIs and nosocomial pneumonia caused by Gram-negative bacteria.
Key word
cefiderocol, complicated urinary tract infection, nosocomial pneumonia, randomized controlled trial, post-hoc analysis
Received
December 26, 2024
Accepted
February 3, 2025
Jpn. J. Chemother. 73 (S-1): 44-53, 2025
