重新利用fda批准的药物对抗抗菌素耐药性的机制框架:金黄色葡萄球菌的案例。

IF 13.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Daniel Sun, Victor Nizet
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引用次数: 0

摘要

抗生素耐药细菌的全球崛起对医疗保健系统构成了严重威胁,这对研究人员保持领先于不断进化的病原体构成了挑战。其中最令人担忧的是由金黄色葡萄球菌(SA)引起的侵袭性感染,尽管护理取得了进步,但发病率和死亡率仍然很高。在引入新的抗生素后,SA的耐药性迅速出现,限制了治疗选择,并促使迫切需要替代方案。虽然开发新的抗菌剂仍然至关重要,但重新利用fda批准的药物(最初用于非感染性适应症)提供了一种补充策略。这些药物具有已知的安全性和药代动力学特征,并可能影响细菌毒力、抗生素敏感性或宿主免疫以改善结果。本文综述了SA药物再利用的最新进展,重点介绍了六个机制类别:抑制毒力因子、抗生素再敏化、增强对先天免疫的易感性、宿主细胞保护、增强免疫功能和调节病理性炎症。总之,这些策略提供了一个多方面的框架,以改善SA感染的结果使用现有的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Mechanistic Framework for Repurposing FDA-Approved Drugs to Combat Antimicrobial Resistance: The Case of Staphylococcus aureus.

The global rise of antibiotic-resistant bacteria poses a critical threat to healthcare systems, challenging researchers to stay ahead of evolving pathogens. Among the most concerning are invasive infections caused by Staphylococcus aureus (SA), where morbidity and mortality remain high despite advances in care. Resistance in SA has emerged rapidly after the introduction of new antibiotics, limiting treatment options and prompting an urgent need for alternatives. While developing new antimicrobials remains essential, repurposing FDA-approved drugs-originally developed for noninfectious indications-offers a complementary strategy. These agents have known safety and pharmacokinetic profiles and may impact bacterial virulence, antibiotic susceptibility, or host immunity to improve outcomes. This review highlights recent advances in SA drug repurposing, focusing on six mechanistic categories: inhibition of virulence factors, antibiotic resensitization, enhanced susceptibility to innate immunity, host cell protection, augmentation of immune functions, and modulation of pathological inflammation. Together, these strategies offer a multifaceted framework to improve SA infection outcomes using existing therapeutics.

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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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