Cefiderocol: a novel siderophore cephalosporin
Cefiderocol: a novel siderophore cephalosporin
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DOI：
10.1080/13543784.2018.1426745
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发表时间：
2018-01-01
影响因子：
6.1
通讯作者：
McCarthy, Matthew W.
中科院分区：
文献类型：
--
作者：
Choi, Justin J.;McCarthy, Matthew W.
前言：多重耐药细菌病原体的出现导致了全球公共卫生危机，迫切需要新的治疗方案和药物输送系统。头孢地洛是一种含铁载体头孢菌素抗生素，最近开发出来用于对抗多种细菌病原体，包括对β-内酰胺类和碳青霉烯类耐药的细菌。内容包括：本文概述了β-内酰胺类和碳青霉烯类耐药的突变和质粒介导的机制，铁载体在细菌铁代谢中的生化途径，以及头孢地洛如何能够提供更好的靶向抗菌治疗，从而避开这些耐药机制。我们还探讨了这种新化合物的药代动力学以及临床前和临床研究的结果。专家观点：迫切需要新的抗菌剂来解决多重耐药病原体的出现，这是全球发病率和死亡率日益增长的原因。我们对多药耐药和细菌生化途径的了解不断扩大，针对铁载体介导的铁转运的头孢地洛的开发显示了在逃避耐药机制方面的潜力。头孢地洛显示出良好的副作用，有可能成为我们最具侵略性和致命的多重耐药革兰氏阴性病原体的一线治疗方法。
Introduction: The emergence of multidrug-resistant bacterial pathogens has led to a global public health emergency and novel therapeutic options and drug-delivery systems are urgently needed. Cefiderocol is a siderophore cephalosporin antibiotic that has recently been developed to combat a variety of bacterial pathogens, including beta-lactam- and carbapenem-resistant organisms.Areas covered: This paper provides an overview of the mutational and plasmid-mediated mechanisms of beta-lactam and carbapenem resistance, the biochemical pathways of siderophores in bacterial iron metabolism, and how cefiderocol may be able to provide better targeted antimicrobial therapy that escape these drug-resistant mechanisms. We also explore the pharmacokinetics of this new compound as well as results from preclinical and clinical studies.Expert opinion: There is an urgent need for novel antimicrobial agents to address the emergence of multidrug-resistant pathogens, which are an increasing cause of morbidity and mortality worldwide. Our understanding of multidrug-resistance and bacterial biochemical pathways continues to expand, and the development of cefiderocol specifically targeting siderophore-mediated iron transport shows potential in escaping mechanisms of drug resistance. Cefiderocol, which demonstrates a favorable side effect profile, has the potential to become first-line therapy for our most aggressive and lethal multidrug-resistant Gram-negative pathogens.