Department of Biology, San Diego State University, San Diego, CA, USA.
Department of Biology, San Diego State University, San Diego, CA, USA; Viral Information Institute, San Diego State University, San Diego, CA, USA.
Clin Ther. 2020 Sep;42(9):1659-1680. doi: 10.1016/j.clinthera.2020.07.014. Epub 2020 Aug 31.
Widespread antibiotic-resistant bacteria are threatening the arsenal of existing antibiotics. Not only are antibiotics less likely to be effective today, but their extensive use continues to drive the emergence of multidrug-resistant pathogens. A new-old antibacterial strategy with bacteriophages (phages) is under development, namely, phage therapy. Phages are targeted bacterial viruses with multiple antibacterial effector functions, which can reduce multidrug-resistant infections within the human body. This review summarizes recent phage therapy clinical trials and patient cases and outlines the fundamentals behind phage treatment strategies under development, mainly through bench-to-bedside approaches. We discuss the challenges that remain in phage therapy and the role of phages when combined with antibiotic therapy.
This narrative review presents the current knowledge and latest findings regarding phage therapy. Relevant case reports and research articles available through the Scopus and PubMed databases are discussed.
Although recent clinical data suggest the tolerability and, in some cases, efficacy of phage therapy, the clinical functionality still requires careful definition. The lack of well-controlled clinical trial data and complex regulatory frameworks have driven the most recent human data generation on a single-patient compassionate use basis. These cases often include the concomitant use of antibiotics, which makes it difficult to draw conclusions regarding the effectiveness of phages alone. However, human data support using antibiotics as phage potentiators and resistance breakers; thus, phage adjuvants are a promising avenue for near-term clinical development. Current knowledge gaps exist on the appropriate routes of administration, phage selection, frequency of administration, dosage, phage resistance, and pharmacokinetic and pharmacodynamic properties of the phages. In addition, we highlight that some phage therapies have mild adverse effects in patients.
Although more translational research is needed before the clinical implementation is feasible, phage therapy may well be pivotal in safeguarding humans against antibiotic-resistant infections.
广泛存在的抗生素耐药细菌正在威胁现有的抗生素储备。不仅抗生素现在不太可能有效，而且它们的广泛使用还在继续推动多药耐药病原体的出现。一种新的古老的抗菌策略——噬菌体（phages）疗法正在开发中。噬菌体是靶向细菌的病毒，具有多种抗菌效应子功能，可以减少人体内的多药耐药感染。这篇综述总结了最近的噬菌体治疗临床试验和病例，并概述了正在开发的噬菌体治疗策略背后的基本原理，主要是通过从实验室到病床的方法。我们讨论了噬菌体治疗仍然存在的挑战以及噬菌体与抗生素治疗联合使用的作用。
本叙述性综述介绍了噬菌体治疗的现有知识和最新发现。讨论了通过 Scopus 和 PubMed 数据库可获得的相关病例报告和研究文章。
尽管最近的临床数据表明噬菌体治疗具有耐受性，并且在某些情况下具有疗效，但临床功能仍需要仔细定义。缺乏良好对照的临床试验数据和复杂的监管框架促使最近的人类数据是基于单一患者的同情使用基础上生成的。这些病例通常包括抗生素的同时使用，这使得很难得出关于噬菌体单独有效性的结论。然而，人体数据支持将抗生素用作噬菌体增效剂和耐药性破坏剂；因此，噬菌体佐剂是近期临床开发的一个有前途的途径。目前在适当的给药途径、噬菌体选择、给药频率、剂量、噬菌体耐药性以及噬菌体的药代动力学和药效学特性方面存在知识空白。此外，我们强调一些噬菌体疗法在患者中会产生轻微的副作用。
尽管在临床实施可行之前需要进行更多的转化研究，但噬菌体治疗很可能是保护人类免受抗生素耐药感染的关键。
