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NP108,一种具有抗耐甲氧西林和莫匹罗星金黄色葡萄球菌活性的抗菌聚合物。

NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus.

机构信息

NovaBiotics Ltd., Craibstone, Aberdeen, United Kingdom

NovaBiotics Ltd., Craibstone, Aberdeen, United Kingdom.

出版信息

Antimicrob Agents Chemother. 2017 Aug 24;61(9). doi: 10.1128/AAC.00502-17. Print 2017 Sep.

Abstract

is a clinically significant human pathogen that causes infectious diseases ranging from skin and soft tissue infections (SSTI) and health care-associated infections (HAI) to potentially fatal bacteremia and endocarditis. Nasal carriage of , especially for persistent carriage, is associated with an increased risk of subsequent infection, particularly nosocomial and surgical site infections (SSI), usually via autoinfection. NP108 is a cationic antimicrobial polymer composed of generally recognized as safe (GRAS) amino acid building blocks. NP108 is broad spectrum and rapidly bactericidal (3-log kill in ≤3 h), killing bacteria by membrane disruption and cell lysis. NP108, contrary to many antibiotics, shows equally effective antimicrobial activity against a variety of (MIC = 8 to 500 mg/liter) and (MIC = 4 to 8 mg/liter) isolates, whether exponentially growing or in stationary phase. NP108 is antimicrobially active under nutrient-limiting conditions similar to those found in the anterior nares (MIC = 8 mg/liter) and kills antibiotic-resilient small colony variants (MIC = 32 mg/liter) and biofilms (prevention, MIC = 1 to 4 mg/liter; eradication, MIC ≥ 31.25 mg/liter). NP108 is active against isolates of resistant to the current standard-of-care decolonization agent, mupirocin, with no significant increase in the MIC NP108 is water soluble and has been formulated into compatible aqueous gel vehicles for human use in which antimicrobial efficacy is retained (2.0% [wt/vol]). NP108 is a potential nonantibiotic antimicrobial alternative to antibiotics for the nasal decolonization of , with clear advantages in its mechanism of action over the existing gold standard, mupirocin.

摘要

是一种临床上重要的人类病原体,可引起从皮肤和软组织感染(SSTI)和与医疗保健相关的感染(HAI)到潜在致命的菌血症和心内膜炎等传染病。 的鼻腔携带,特别是持续性携带,与随后感染的风险增加有关,特别是医院获得性和手术部位感染(SSI),通常通过自体感染。 NP108 是一种由通常被认为是安全的(GRAS)氨基酸构建块组成的阳离子抗菌聚合物。 NP108 广谱且快速杀菌(≤3 小时内 3 对数杀灭),通过破坏细胞膜和细胞溶解来杀死细菌。与许多抗生素不同,NP108 对各种 (MIC = 8 至 500 毫克/升)和 (MIC = 4 至 8 毫克/升)分离株表现出同样有效的抗菌活性,无论是指数生长期还是静止期。 NP108 在类似于前鼻孔中发现的营养有限条件下具有抗菌活性(MIC = 8 毫克/升),并杀死具有抗生素抗性的小菌落变体(MIC = 32 毫克/升)和 生物膜(预防,MIC = 1 至 4 毫克/升;消除,MIC ≥ 31.25 毫克/升)。 NP108 对耐当前标准护理去定植剂莫匹罗星的 分离株有效,而 NP108 的 MIC 没有显着增加。 NP108 水溶性,并已配制成适用于人体的相容水性凝胶载体,其中保留了抗菌功效(2.0%[重量/体积])。 NP108 是一种潜在的非抗生素抗菌替代抗生素,可用于 鼻腔去定植,其作用机制明显优于现有金标准莫匹罗星。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55ea/5571353/6daf194573d5/zac0091764480001.jpg

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