Vol.73 No.S-1 April 2025
Phase III clinical trial of cefiderocol in patients with carbapenem-resistant Gram-negative bacterial infections (CREDIBLE-CR Study)
1)School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan
2)Department of Laboratory Medicine, Nagasaki University
3)Department of Clinical Infectious Diseases, Aichi Medical University
4)Departments of Microbiology and Infectious Diseases, Fujita Health University, School of Medicine
Abstract
The CREDIBLE-CR study was conducted as open-label, multicentre, parallel-group, pathogen-focused, descriptive, phase III study for cefiderocol (CFDC) and best available therapy (BAT). Of the 150 patients enrolled, 101 were assigned to the CFDC group and 49 to the BAT group. Sixty-seven patients (45%) had nosocomial pneumonia, 47 (31%) had a bloodstream infection or sepsis, and 36 (24%) had a complicated urinary tract infection. Carbapenem-resistant bacteria were isolated from 118 patients (80 in the CFDC group and 38 in the BAT group), and the most common species were Acinetobacter baumannii (54 patients [46%]), Klebsiella pneumoniae (39 patients [33%]), and Pseudomonas aeruginosa (22 patients [19%]).
In the nosocomial pneumonia group, a clinical cure was achieved in 50.0% of the patients in the CFDC group and 52.6% of the patients in the BAT group. In the bloodstream infections or sepsis group, 43.5% in the CFDC group and 42.9% in the BAT group were cured. In the complicated urinary tract infection group, microbiological eradication was achieved in 52.9% in the CFDC group and 20.0% in the BAT group. CFDC demonstrated favorable clinical and microbiological effects regardless of the species of bacteria.
On the other hand, the all-cause mortality rate at the end of the study was higher in the CFDC group (33.7%) than in the BAT group (18.4%), and this finding may have been influenced by the fact that there were more deaths among the patients with Acinetobacter infections. However, post-hoc analyses have not revealed any definitive causes for the higher mortality rate in the CFDC group, including any differences in patient background or presence of heteroresistance.
Overall, the CREDIBLE-CR study confirmed the efficacy and safety of CFDC in the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, including OXA-48-producing strains and MBL-producing strains.
Key word
cefiderocol, carbapenems, Gram-negative bacteria, drug-resistant bacteria
Received
January 9, 2025
Accepted
February 17, 2025
Jpn. J. Chemother. 73 (S-1): 34-43, 2025
