Vol.73 No.S-1 April 2025
Results of a non-clinical pharmacology study of the antibacterial activities of cefiderocol against Gram-negative bacteria
1)Pharmaceutical Research Division, Shionogi & Co., Ltd., 3-1-1 Futaba, Toyonaka, Osaka, Japan
2)Department of Clinical Infectious Diseases, Aichi Medical University
Abstract
Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits excellent antibacterial activity against all Gram-negative bacteria, including carbapenem-resistant strains. CFDC has a unique structural feature wherein it forms a complex with iron and is actively incorporated into bacterial cells via iron-transportation systems. Therefore, the antibacterial activity of CFDC is significantly affected by the iron uptake activity of the bacteria. The standard protocol of the Clinical and Laboratory Standards Institute requires the use of an iron-deficient medium for measurement of the minimum inhibitory concentration (MIC) of CFDC, which is known to be correlated with the drug efficacy in animal infection models.
In the SIDERO-WT-2014-2019 study, a global surveillance study conducted mainly in Europe and the United States, the values of MIC90, the drug concentration required for 90% inhibition of bacterial growth, against all the Gram-negative bacteria tested were 1 μg/mL or less ≤1 mg/mL. CFDC also exhibited good activity against meropenem non-susceptible sub set strains. In the SIDERO-CR-2014/2016 study, which was focused on carbapenem-resistant clinical isolates from around the world, CFDC exhibited potent activity, regardless of the bacterial species or carbapenemase types carbapenem sensitivity. Both studies demonstrated the strong antibacterial activity of CFDC against metallo-β-lactamase-producing strains that are resistant to clinically available cephalosporins and β-lactam/β-lactamase inhibitors.
Some kinds of β-lactamases, such as PER/VEB and NDM, have been reported to be involved in decreasing the susceptibility to CFDC. However, it has been reported that CFDC resistance with a combination of different mechanisms, including decreased expression of siderophore receptors related to the iron transport pathway, penicillin-binding protein mutations, etc.
Key word
cefiderocol, in vitro, MIC
Received
November 15, 2024
Accepted
December 23, 2024
Jpn. J. Chemother. 73 (S-1): 8-16, 2025
