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头孢地尔:一种用于治疗多重耐药革兰氏阴性菌的新型药物。

Cefiderocol: A Novel Agent for the Management of Multidrug-Resistant Gram-Negative Organisms.

作者信息

Wu Janet Y, Srinivas Pavithra, Pogue Jason M

机构信息

Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.

College of Pharmacy, University of Michigan, Ann Arbor, MI, USA.

出版信息

Infect Dis Ther. 2020 Mar;9(1):17-40. doi: 10.1007/s40121-020-00286-6. Epub 2020 Feb 18.

Abstract

Cefiderocol, formerly S-649266, is a first in its class, an injectable siderophore cephalosporin that combines a catechol-type siderophore and cephalosporin core with side chains similar to cefepime and ceftazidime. This structure and its unique mechanism of action confer enhanced stability against hydrolysis by many β-lactamases, including extended spectrum β-lactamases such as CTX-M, and carbapenemases such as KPC, NDM, VIM, IMP, OXA-23, OXA-48-like, OXA-51-like and OXA-58. Cefiderocol's spectrum of activity encompasses both lactose-fermenting and non-fermenting Gram-negative pathogens, including carbapenem-resistant Enterobacterales. Cefiderocol recently received US Food and Drug Administration approval for the treatment of complicated urinary tract infections, including pyelonephritis, and is currently being evaluated in phase III trials for nosocomial pneumonia and infections caused by carbapenem-resistant Gram-negative pathogens. The purpose of this article is to review existing data on the mechanism of action, microbiology, pharmacokinetics, pharmacodynamics, efficacy, and safety of cefiderocol to assist clinicians in determining its place in therapy.

摘要

头孢地尔,原称S-649266,是该类药物中的首个产品,是一种可注射的铁载体头孢菌素,它将儿茶酚型铁载体和头孢菌素核心与类似于头孢吡肟和头孢他啶的侧链相结合。这种结构及其独特的作用机制使其对多种β-内酰胺酶(包括超广谱β-内酰胺酶如CTX-M,以及碳青霉烯酶如KPC、NDM、VIM、IMP、OXA-23、OXA-48样、OXA-51样和OXA-58)的水解具有更高的稳定性。头孢地尔的活性谱涵盖了发酵乳糖和不发酵乳糖的革兰氏阴性病原体,包括耐碳青霉烯类肠杆菌科细菌。头孢地尔最近获得了美国食品药品监督管理局的批准,用于治疗复杂性尿路感染,包括肾盂肾炎,目前正在进行治疗医院获得性肺炎和耐碳青霉烯类革兰氏阴性病原体所致感染的Ⅲ期试验。本文的目的是综述关于头孢地尔作用机制、微生物学、药代动力学、药效学、疗效和安全性的现有数据,以帮助临床医生确定其在治疗中的地位。

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