Murepavadin: a new antibiotic class in the pipeline
Murepavadin: a new antibiotic class in the pipeline
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DOI：
10.1080/14787210.2018.1441024
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发表时间：
2018-01-01
影响因子：
5.7
通讯作者：
Torres, Antoni
中科院分区：
文献类型：
--
作者：
Martin-Loeches, Ignacio;Dale, Glenn E.;Torres, Antoni
简介：随着多重耐药铜绿假单胞菌的增加，需要具有新作用机制的抗菌药物来靶向这些感染。涵盖领域：静脉注射murepavadin处于3期开发阶段，用于治疗由铜绿假单胞菌引起的HABP/VABP。本文总结了murepavadin的发现、体外活性、药代动力学和药效学特性以及迄今为止的临床药理学方面的可用信息。专家评论：铜绿假单胞菌对许多抗生素具有内在的耐药性，这是由于高细胞不渗透性和有效的药物外排机制，并且最近多药耐药铜绿假单胞菌感染的流行率增加在ICU环境中特别具有威胁性。Murepavadin是一种病原体特异性抗菌肽模拟物，具有新型的非溶解作用机制，是正在开发的第一类靶向外膜蛋白的抗生素。Murepavadin显示出强效体外活性，包括产碳青霉烯酶和粘菌素耐药铜绿假单胞菌。Murepavadin在临床前动物模型（包括XDR分离株感染）中具有活性。包括肾功能受损受试者和VABP患者在内的药代动力学特征良好。静脉注射murepavadin目前正在临床开发中，用于治疗铜绿假单胞菌感染引起的HABP/VABP。
Introduction: With the increase in multi-drug resistant P. aeruginosa, antimicrobials with a novel mechanism of action are needed that can target these infections.Areas covered: Intravenous murepavadin is in Phase 3 development for the treatment of HABP/VABP due to P. aeruginosa. This paper summarizes the available information on the discovery, the in vitro activity, pharmacokinetic and pharmacodynamic properties and the clinical pharmacology of murepavadin to date.Expert commentary: P. aeruginosa has an intrinsic resistance to many antibiotics due to high cellular impermeability and efficient drug efflux mechanisms, and the recent increase in prevalence of multidrug-resistant P. aeruginosa infections are particularly threatening in ICU settings. Murepavadin is a pathogen specific antimicrobial peptidomimetic with a novel, non-lytic mechanism of action, and is the first in class of outer membrane protein targeting antibiotics which are being developed. Murepavadin displays a potent in vitro activity including carbapenemase-producing and colistin-resistant P. aeruginosa. Murepavadin is active in pre-clinical animal models including infections with XDR isolates. The Pharmacokinetics is well characterized including subjects with impaired renal function and patients with VABP. Intravenous murepavadin is currently under clinical development for the treatment of HABP/VABP due to P. aeruginosa infection.