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葡萄球菌之战:抗生素管道奋起反击。

Staph wars: the antibiotic pipeline strikes back.

机构信息

Department of Life Sciences, University of Bath, Bath BA2 7AY, UK.

出版信息

Microbiology (Reading). 2023 Sep;169(9). doi: 10.1099/mic.0.001387.

Abstract

Antibiotic chemotherapy is widely regarded as one of the most significant medical advancements in history. However, the continued misuse of antibiotics has contributed to the rapid rise of antimicrobial resistance (AMR) globally. , a major human pathogen, has become synonymous with multidrug resistance and is a leading antimicrobial-resistant pathogen causing significant morbidity and mortality worldwide. This review focuses on (1) the targets of current anti-staphylococcal antibiotics and the specific mechanisms that confirm resistance; (2) an in-depth analysis of recently licensed antibiotics approved for the treatment of infections; and (3) an examination of the pre-clinical pipeline of anti-staphylococcal compounds. In addition, we examine the molecular mechanism of action of novel antimicrobials and derivatives of existing classes of antibiotics, collate data on the emergence of resistance to new compounds and provide an overview of key data from clinical trials evaluating anti-staphylococcal compounds. We present several successful cases in the development of alternative forms of existing antibiotics that have activity against multidrug-resistant . Pre-clinical antimicrobials show promise, but more focus and funding are required to develop novel classes of compounds that can curtail the spread of and sustainably control antimicrobial-resistant infections.

摘要

抗生素化疗被广泛认为是历史上最重要的医学进展之一。然而,抗生素的持续滥用导致了全球范围内抗菌药物耐药性(AMR)的迅速上升。金黄色葡萄球菌作为一种主要的人类病原体,已经成为多药耐药的代名词,是导致全球发病率和死亡率显著升高的主要抗菌药物耐药病原体。本综述重点关注(1)目前抗葡萄球菌抗生素的作用靶点和确证耐药的具体机制;(2)深入分析最近批准用于治疗 感染的抗生素;(3)研究抗葡萄球菌化合物的临床前研发管线。此外,我们还研究了新型抗菌药物和现有类别抗生素衍生物的作用机制,整理了新型化合物耐药性出现的数据,并概述了评估抗葡萄球菌化合物的临床试验的关键数据。我们介绍了几种现有抗生素替代形式开发的成功案例,这些替代形式对多药耐药 具有活性。临床前抗菌药物显示出良好的前景,但需要更多的关注和资金来开发新型化合物类别,以遏制和可持续控制抗菌药物耐药性 感染的传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/db44/10569064/8702bd5c4150/mic-169-1387-g001.jpg

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