A Novel Antibiotic Agent, Cefiderocol, for Multidrug-Resistant Gram-Negative Bacteria

Abstract

ƒThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ license/by-nc/3.0/). The threat of antibiotic resistance is an influencing factor in deteriorating public health. Therefore, new antibiotic development is necessary for continued successful treatment of infectious diseases. Cefiderocol is the first licensed injectable siderophore cephalosporin that chemically conjugates a siderophore and cephalosporin. Due to its high stability against various β-lactamases, it is widely used as an effective antibiotic for multidrug-resistant (MDR) gram-negative microorganisms, including Acinetobacter baumannii, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae. Cefiderocol blocks microbial cell membrane synthesis. The binding site of cefiderocol is a penicillin-binding protein. Because of its siderophore-like properties, cefiderocol penetrates gram-negative bacterial periplasmic spaces, increasing its stability against β-lactamases. Unlike earlier cephalosporins, the siderophore of the cefiderocol moiety at position C-3 chelates with iron (ferric form) in the host and is then actively transported into the bacterial periplasmic space. This approach is known as a “Trojan horse” and improves cefiderocol stability against efflux pumps as well as porin channel mutations. Modification at the C-3 and C-7 side-chains produces powerful antibacterial properties against MDR gram-negative bacteria. The U.S. Food and Drug Administration (FDA) approved it as a new treatment option for adult patients with complicated urinary tract infection (cUTI) who have limited and no treatment options. Based on these observations, we conclude that cefiderocol is a potent treatment option for prospective bacterial infections. In this review, we summarize the future prospective use of cefiderocol for bacterial infections.