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用于多重耐药感染的噬菌体疗法:当前技术与治疗方法

Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches.

作者信息

Kim Minyoung Kevin, Suh Gina A, Cullen Grace D, Perez Rodriguez Saumel, Dharmaraj Tejas, Chang Tony Hong Wei, Li Zhiwei, Chen Qingquan, Green Sabrina I, Lavigne Rob, Pirnay Jean-Paul, Bollyky Paul L, Sacher Jessica C

机构信息

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, California, USA.

Department of Medicine, Yale University, New Haven, Connecticut, USA.

出版信息

J Clin Invest. 2025 Mar 3;135(5):e187996. doi: 10.1172/JCI187996.

Abstract

Bacteriophage (phage) therapy has emerged as a promising solution to combat the growing crisis of multidrug-resistant (MDR) infections. There are several international centers actively engaged in implementation of phage therapy, and recent case series have reported encouraging success rates in patients receiving personalized, compassionate phage therapy for difficult-to-treat infections. Nonetheless, substantial hurdles remain in the way of more widespread adoption and more consistent success. This Review offers a comprehensive overview of current phage therapy technologies and therapeutic approaches. We first delineate the common steps in phage therapy development, from phage bank establishment to clinical administration, and examine the spectrum of therapeutic approaches, from personalized to fixed phage cocktails. Using the framework of a conventional drug development pipeline, we then identify critical knowledge gaps in areas such as cocktail design, formulation, pharmacology, and clinical trial design. We conclude that, while phage therapy holds promise, a structured drug development pipeline and sustained government support are crucial for widespread adoption of phage therapy for MDR infections.

摘要

噬菌体疗法已成为应对日益严重的多重耐药(MDR)感染危机的一种有前景的解决方案。有几个国际中心积极致力于噬菌体疗法的实施,最近的病例系列报告显示,接受个性化、个体化噬菌体疗法治疗难治性感染的患者成功率令人鼓舞。尽管如此,在更广泛采用和更持续取得成功方面仍存在重大障碍。本综述全面概述了当前的噬菌体疗法技术和治疗方法。我们首先描述了噬菌体疗法从噬菌体库建立到临床给药的常见开发步骤,并研究了从个性化到固定噬菌体鸡尾酒疗法的治疗方法范围。然后,我们利用传统药物开发流程的框架,确定了鸡尾酒疗法设计、制剂、药理学和临床试验设计等领域的关键知识空白。我们得出结论,虽然噬菌体疗法前景广阔,但结构化的药物开发流程和政府的持续支持对于广泛采用噬菌体疗法治疗多重耐药感染至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c38/11870740/dba0520186d9/jci-135-187996-g173.jpg

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