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治疗耐甲氧西林金黄色葡萄球菌生物膜相关感染的抗生素耐药性的策略。

Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm-Associated Infections.

机构信息

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123, Palermo, Italy.

Department of Medical Oncology Cancer Center Amsterdam, VU University Medical Center (VUmc), De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.

出版信息

ChemMedChem. 2021 Jan 8;16(1):65-80. doi: 10.1002/cmdc.202000677. Epub 2020 Nov 6.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the leading causes of persistent human infections. This pathogen is widespread and is able to colonize asymptomatically about a third of the population, causing moderate to severe infections. It is currently considered the most common cause of nosocomial infections and one of the main causes of death in hospitalized patients. Due to its high morbidity and mortality rate and its ability to resist most antibiotics on the market, it has been termed a "superbug". Its ability to form biofilms on biotic and abiotic surfaces seems to be the primarily means of MRSA antibiotic resistance and pervasiveness. Importantly, more than 80 % of bacterial infections are biofilm-mediated. Biofilm formation on indwelling catheters, prosthetic devices and implants is recognized as the cause of serious chronic infections in hospital environments. In this review we discuss the most relevant literature of the last five years concerning the development of synthetic small molecules able to inhibit biofilm formation or to eradicate or disperse pre-formed biofilms in the fight against MRSA diseases. The aim is to provide guidelines for the development of new anti-virulence strategies based on the knowledge so far acquired, and, to identify the main flaws of this research field, which have hindered the generation of new market-approved anti-MRSA drugs that are able to act against biofilm-associated infections.

摘要

耐甲氧西林金黄色葡萄球菌(MRSA)已成为持续性人类感染的主要病原体之一。这种病原体广泛存在,能够无症状地定植于约三分之一的人群中,引起中度至重度感染。目前,它被认为是医院感染的最常见原因之一,也是住院患者死亡的主要原因之一。由于其高发病率和死亡率,以及对市场上大多数抗生素的耐药性,它被称为“超级细菌”。它在生物和非生物表面形成生物膜的能力似乎是其抗生素耐药性和普遍性的主要手段。重要的是,超过 80%的细菌感染是由生物膜介导的。在留置导管、假体装置和植入物上形成生物膜被认为是导致医院环境中严重慢性感染的原因。在这篇综述中,我们讨论了过去五年中与开发能够抑制生物膜形成或消除或分散预先形成的生物膜的合成小分子有关的最相关文献,以对抗 MRSA 疾病。目的是为基于迄今获得的知识开发新的抗毒力策略提供指导,并确定该研究领域的主要缺陷,这些缺陷阻碍了新的、经市场批准的抗 MRSA 药物的产生,这些药物能够对抗与生物膜相关的感染。

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