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对抗多重耐药菌的综合策略:为全球健康合成新型抗菌前沿。

Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health.

作者信息

Rathored Jaishriram, Budhbaware Tanushree

机构信息

Central Research Laboratory and Molecular Diagnostics, School of Allied Health Sciences, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Postal code 442001, Wardha, Maharashtra, India.

Central Research Laboratory and Molecular Diagnostics, School of Allied Health Sciences, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Postal code 442001, Wardha, Maharashtra, India.

出版信息

Microb Pathog. 2025 Nov;208:108018. doi: 10.1016/j.micpath.2025.108018. Epub 2025 Sep 4.

Abstract

Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies.

摘要

令人担忧的是,多重耐药菌已成为全球主要难题,阻碍了传染病的治疗,并引发了对现有药物治疗偶然性的质疑。由于传统抗生素无法跟上细菌进化的步伐,新型抗菌干预措施值得研发。本文综述了各种对抗多重耐药菌感染的有前景的方法。研究了抗菌肽的广谱疗效和较低的耐药性产生能力,而噬菌体疗法可在抗生素失效的极端情况下使用。此外,还将探索CRISPR-Cas系统特异性靶向和消除细菌群体中耐药基因的可能性。纳米技术为改善药物本身的递送系统开辟了道路,提高了抗菌作用的疗效和特异性,同时保护了宿主。通过合成生物学的发展和基于天然产物药物的重新发现,发现潜在的抗菌剂是一个令人兴奋的前景。此外,宿主导向疗法作为治疗主要策略的辅助手段,在不专门针对病原体的情况下正变得越来越流行。尽管这些进展令人印象深刻,但关于生产规模扩大、监管批准、安全性以及临床应用的有效性等问题仍然突出。因此,应对多重耐药菌的负担需要一个多管齐下的计划,将新的治疗方式与现有的抗生素治疗方案相结合,加强有力的管理举措,并在全球层面实现政策变革。如果鼓励跨学科机构之间的合作和持续的研究努力,国际卫生界可以抵御日益增长的抗生素耐药性威胁。在本研究中,我们除了总结近期进展外,还评估了联合使用各种药物的协同潜力。为了重新思考未来的抗菌管理,我们提供了一个结合病原体聚焦和宿主导向策略的多层次范式。

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