针对异种和万古霉素中间体金黄色葡萄球菌的新兴抗菌策略。

IF 2 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of General Medicine Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI:10.2147/IJGM.S532471
Yaru Wang, Yanwen Sun, Guang Chen, Xin Cheng
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引用次数: 0

摘要

异质性万古霉素中间体和万古霉素中间体金黄色葡萄球菌(hVISA和VISA)由于高治疗失败率和有限的选择,提出了重大的治疗挑战。传统的单药治疗,包括达托霉素和利奈唑胺,经常受到交叉耐药和疗效不一致的影响。结合β-内酰胺类、喹诺酮类或脂肽与万古霉素的联合治疗利用协同机制(如“跷跷板效应”),但根据菌株、药物浓度和实验模型表现出不同的成功。新型抗菌剂,如新一代糖肽(LY333328、oritavancin、YV4465)、合成制剂(吡啶二硫化物、α -amyrin)和天然衍生物(植物黄酮类化合物、蓝细菌代谢物),已经通过破坏膜、抑制毒力或逆转耐药性,证明了对VISA/hVISA的增强活性。抗菌肽和非经典药物(如新霉素、泰罗霉素)通过靶向RNA降解、生物膜或毒素产生进一步扩大了治疗选择。此外,先进的药物传递系统,包括纳米乳剂和纳米脂质体,提高了药物稳定性、生物膜渗透和局部疗效。尽管取得了这些有希望的进展,但临床转化仍然具有挑战性,需要严格验证协同机制、优化给药策略和减轻耐药性的方法。抗菌素开发的持续创新对于解决耐多药金黄色葡萄球菌感染日益严重的威胁至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Emerging Antimicrobial Strategies Against Heterogeneous and Vancomycin-Intermediate <i>Staphylococcus aureus</i>.

Emerging Antimicrobial Strategies Against Heterogeneous and Vancomycin-Intermediate Staphylococcus aureus.

Heterogeneous vancomycin-intermediate and vancomycin-intermediate Staphylococcus aureus (hVISA and VISA) presents significant therapeutic challenges due to high treatment failure rates and limited options. Conventional monotherapies, including daptomycin and linezolid, are often compromised by cross-resistance and inconsistent efficacy. Combination therapies incorporating β-lactams, quinolones, or lipopeptides with vancomycin exploit synergistic mechanisms (eg, the "seesaw effect") but exhibit variable success depending on bacterial strain, drug concentration, and experimental models. Novel antimicrobials, such as next-generation glycopeptides (LY333328, oritavancin, YV4465), synthetic agents (pyridyl disulfides, alpha-amyrin), and natural derivatives (plant flavonoids, cyanobacterial metabolites), have demonstrated enhanced activity against VISA/hVISA by disrupting membranes, suppressing virulence, or reversing resistance. Antimicrobial peptides and non-classical agents (eg, nybomycin, telomycin) further expand therapeutic options by targeting RNA degradation, biofilms, or toxin production. Additionally, advanced drug delivery systems, including nanoemulsions and nanoliposomes, improve drug stability, biofilm penetration, and localized efficacy. Despite these promising advances, clinical translation remains challenging, requiring rigorous validation of synergistic mechanisms, optimized dosing strategies, and resistance mitigation approaches. Continued innovation in antimicrobial development is essential to address the growing threat of multidrug-resistant Staphylococcus aureus infections.

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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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