OBJECTIVE This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages. METHODS First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed. RESULTS Over the past decade the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo. CONCLUSION Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy, however reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials.

中文翻译：

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噬菌体疗法作为抗生素耐药性感染替代治疗方法的潜力。

目的 本研究旨在全面概述噬菌体治疗应用文献的现状。方法 首先，使用数据库 Web of Science 进行文献计量分析，以确定每年的出版物和引用数量。其次，对 PubMed 中噬菌体疗法的随机对照试验（RCT）进行了系统的文献综述。结果 在过去十年中，有关噬菌体疗法的出版物数量增加了四倍多，2011 年有 212 篇文章，2022 年有 739 篇文章。PubMed 的系统检索产生了 7 项符合纳入报告的随机对照试验，总共涉及 418 名参与者。这项研究确定的适应症包括细菌性腹泻、尿路感染、感染烧伤伤口、慢性中耳炎、慢性静脉性腿部溃疡和慢性鼻窦炎。在三项研究中，10/195 名参与者 (5.1%) 报告了轻度至中度不良事件。其中三项研究报告称，将噬菌体疗法与标准护理或安慰剂进行比较，结果存在统计学上的显着差异。结论 多年来，噬菌体疗法引起了越来越多的兴趣。针对不同适应症的随机对照试验表明噬菌体疗法的安全性，但噬菌体疗法尚未被广泛接受的原因是研究设计的局限性。为了成功转化为临床实践，研究人员和临床医生应该从早期经验中学习，并考虑噬菌体制备的质量、敏感性测试、效价和剂量等问题，以及标准化方案和未来试验的感染部位和稳定性等问题。