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噬菌体疗法治疗抗生素耐药性细菌感染

Phage Therapy for Antibiotic-Resistant Bacterial Infections.

作者信息

Hatfull Graham F, Dedrick Rebekah M, Schooley Robert T

机构信息

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA; email:

Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA; email:

出版信息

Annu Rev Med. 2022 Jan 27;73:197-211. doi: 10.1146/annurev-med-080219-122208. Epub 2021 Aug 24.

Abstract

Antibiotic resistance in bacterial pathogens presents a substantial threat to the control of infectious diseases. Development of new classes of antibiotics has slowed in recent years due to pressures of cost and market profitability, and there is a strong need for new antimicrobial therapies. The therapeutic use of bacteriophages has long been considered, with numerous anecdotal reports of success. Interest in phage therapy has been renewed by recent clinical successes in case studies with personalized phage cocktails, and several clinical trials are in progress. We discuss recent progress in the therapeutic use of phages and contemplate the key factors influencing the opportunities and challenges. With strong safety profiles, the main challenges of phage therapeutics involve strain variation among clinical isolates of many pathogens, battling phage resistance, and the potential limitations of host immune responses. However, the opportunities are considerable, with the potential to enhance current antibiotic efficacy, protect newly developed antibiotics, and provide a last resort in response to complete antibiotic failure.

摘要

细菌病原体中的抗生素耐药性对传染病的控制构成了重大威胁。由于成本和市场盈利能力的压力,近年来新型抗生素的研发速度有所放缓,因此迫切需要新的抗菌疗法。噬菌体的治疗用途早已被考虑,并有大量成功的轶事报道。近期个性化噬菌体鸡尾酒疗法的病例研究取得临床成功,这使得人们对噬菌体疗法的兴趣再度燃起,并且多项临床试验正在进行中。我们讨论了噬菌体治疗用途的最新进展,并思考了影响机遇和挑战的关键因素。尽管噬菌体疗法具有良好的安全性,但主要挑战包括许多病原体临床分离株之间的菌株差异、对抗噬菌体耐药性以及宿主免疫反应的潜在局限性。然而,其机遇也相当可观,有可能提高当前抗生素的疗效、保护新开发的抗生素,并在抗生素完全失效时提供最后的治疗手段。

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