Yamano Yoshinori, Morita Ippei, Ariyasu Mari
Laboratory for Drug Discovery and Disease Research, Shionogi & Co., Ltd.
Medical Affairs Department, Shionogi & Co., Ltd.
Nihon Yakurigaku Zasshi. 2024;159(5):331-340. doi: 10.1254/fpj.24029.
Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most β-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.
目前,抗菌药物耐药性被公认为全球公共卫生领域的一个紧迫问题。耐碳青霉烯类(CR)革兰氏阴性菌,如肠杆菌科细菌、铜绿假单胞菌和鲍曼不动杆菌,被列为关键病原体,在世卫组织的指南中,它们广泛传播,可导致严重且往往致命的感染。头孢地尔(Fetroja)是一种新型的第一代铁载体头孢菌素,于2023年11月30日在日本被批准用于治疗由这些有问题的CR革兰氏阴性菌引起的感染。头孢地尔具有独特的机制,可利用细菌铁转运系统进入细菌细胞,并对大多数β-内酰胺酶高度稳定,这使其在体外对包括CR菌株在内的这些革兰氏阴性菌具有良好的抗菌活性。在CREDIBLE-CR 3期试验中,头孢地尔对CR革兰氏阴性菌患者显示出良好的疗效和安全性。在APEKS-cUTI和APEKS-NP试验中,头孢地尔分别在复杂性尿路感染(cUTI)患者中显示出非劣效性,并优于亚胺培南/西司他丁,在肺炎患者中显示出与高剂量美罗培南非劣效。头孢地尔有望成为治疗选择有限的CR革兰氏阴性感染的最佳治疗药物,将是对抗CR细菌威胁的重要药物。