Shionogi & Co., Ltd. has announced that the New Drug Application (NDA) for cefiderocol, an injectable antibiotic, has been accepted for priority review by the National Medical Products Administration (NMPA) in China. This marks a significant step toward addressing the growing threat of antimicrobial resistance (AMR) in the region. Cefiderocol is intended for the treatment of serious Gram-negative bacterial infections.
Addressing Gram-Negative Infections
Gram-negative bacteria are a major cause of hospital-acquired infections, and resistance to existing antibiotics is increasing globally. Cefiderocol is designed to combat these infections through a novel mechanism. It acts as a siderophore, binding to ferric iron and utilizing bacterial iron transporters to enter cells actively, bypassing common resistance mechanisms. This allows it to achieve high concentrations in the periplasmic space, where it can effectively inhibit cell wall synthesis.
Cefiderocol's Novel Mechanism
Cefiderocol is the first siderophore cephalosporin antibiotic. Its unique mechanism involves penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore. In addition to entering cells by passive diffusion through porin channels, cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane via bacterial iron transporters. This mechanism allows cefiderocol to achieve high concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells.
The Growing Threat of AMR
Antimicrobial resistance (AMR) is a global public health crisis. In 2019, an estimated 1.27 million deaths worldwide were attributed to AMR. Without concerted international efforts, projections suggest that AMR could cause over 10 million deaths annually by 2050, with a potential cumulative economic impact of up to 100 trillion USD.
Shionogi is actively involved in efforts to combat drug resistance, including collaborative agreements to improve access to cefiderocol in low- and middle-income countries. The priority review in China underscores the urgent need for new antibiotics to combat resistant Gram-negative infections and highlights the potential of cefiderocol to address this critical unmet need.
