Choi Justin J, McCarthy Matthew W
a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
b Division of General Internal Medicine , New York-Presbyterian Hospital , New York , NY , USA.
Expert Opin Investig Drugs. 2018 Feb;27(2):193-197. doi: 10.1080/13543784.2018.1426745. Epub 2018 Jan 24.
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 β-lactam- and carbapenem-resistant organisms.
This paper provides an overview of the mutational and plasmid-mediated mechanisms of β-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.
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.
多重耐药细菌病原体的出现已引发全球公共卫生紧急情况,迫切需要新的治疗选择和药物递送系统。头孢地尔是一种铁载体头孢菌素抗生素,最近被开发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菌株。
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机制、细菌铁代谢中铁载体的生化途径,以及头孢地尔如何能够提供更好的靶向抗菌治疗以规避这些耐药机制。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结果。
迫切需要新型抗菌药物来应对多重耐药病原体的出现,这些病原体在全球范围内导致发病率和死亡率不断上升。我们对多重耐药性和细菌生化途径的理解不断扩展,专门针对铁载体介导的铁转运的头孢地尔的开发显示出规避耐药机制的潜力。头孢地尔具有良好的副作用谱,有可能成为治疗最具侵袭性和致命性的多重耐药革兰氏阴性病原体的一线疗法。