Kline Ahnika, Cobián Güemes Ana G, Yore Jennifer, Ghose Chandrabali, Van Tyne Daria, Whiteson Katrine, Pride David T
Department of Pathology, University of California, San Diego, CA 92093, USA.
Department of Medicine, University of California, San Diego, CA 92093, USA.
Antibiotics (Basel). 2025 May 29;14(6):553. doi: 10.3390/antibiotics14060553.
The resurgence of phage therapy in Western societies has been in direct response to recent increases in antimicrobial resistance (AMR) that have ravaged many societies. While phage therapy as a concept has been around for over 100 years, it has largely been replaced by antibiotics due to their relative ease of use and their predictability in spectrum of activity. Now that antibiotics have become less reliable due to greater antibiotic resistance and microbiome disruption, phage therapy has once again become a viable and promising alternative, but it is not without its challenges. Much like the development of antibiotics, with deployment of phage therapeutics there will be a simultaneous need for diagnostics in the clinical laboratory. This review provides an overview of current challenges to widespread adoption of phage therapy with a focus on adoption in the clinical diagnostic laboratory. Current barriers include a lack of standard methodology and quality controls for phage susceptibility testing and selection, the absence of phage-antibiotic synergy testing, and the absence of standard methods to assay phage activity on biofilms. Additionally, there are a number of lab-specific administrative and regulatory barriers to widespread phage therapy adoption including the need for pharmacokinetic (PK) and pharmacodynamic (PD) assays, methods to account for changes in phages after passaging, an absence of regulatory guidance on what will be required for agency approvals of phages and how broad that approval will apply, and the increased need for lab personnel or automation to account for the work of testing large phage libraries against bacteria isolates.
噬菌体疗法在西方社会的复兴是对近期抗菌药物耐药性(AMR)增加的直接回应,这种耐药性已经对许多社会造成了严重破坏。虽然噬菌体疗法作为一个概念已经存在了100多年,但由于其相对易于使用和活性谱的可预测性,它在很大程度上已被抗生素所取代。现在,由于更强的抗生素耐药性和微生物群破坏,抗生素变得不那么可靠,噬菌体疗法再次成为一种可行且有前景的替代方法,但它并非没有挑战。与抗生素的研发非常相似,随着噬菌体疗法的应用,临床实验室同时也需要诊断方法。本综述概述了目前广泛采用噬菌体疗法面临的挑战,重点是在临床诊断实验室中的应用。当前的障碍包括缺乏用于噬菌体敏感性测试和选择的标准方法和质量控制,缺乏噬菌体 - 抗生素协同作用测试,以及缺乏测定噬菌体对生物膜活性的标准方法。此外,广泛采用噬菌体疗法还存在许多实验室特定的行政和监管障碍,包括需要进行药代动力学(PK)和药效学(PD)测定,解决传代后噬菌体变化的方法,缺乏关于机构批准噬菌体所需条件以及该批准适用范围的监管指导,以及对实验室人员或自动化的需求增加,以处理针对细菌分离株测试大型噬菌体文库的工作。
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