{"title":"Emerging Antimicrobial Strategies Against Heterogeneous and Vancomycin-Intermediate <i>Staphylococcus aureus</i>.","authors":"Yaru Wang, Yanwen Sun, Guang Chen, Xin Cheng","doi":"10.2147/IJGM.S532471","DOIUrl":null,"url":null,"abstract":"<p><p>Heterogeneous vancomycin-intermediate and vancomycin-intermediate <i>Staphylococcus aureus</i> (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 <i>Staphylococcus aureus</i> infections.</p>","PeriodicalId":14131,"journal":{"name":"International Journal of General Medicine","volume":"18 ","pages":"5329-5344"},"PeriodicalIF":2.0000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435363/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of General Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJGM.S532471","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.