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Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches
Minyoung Kevin Kim, … , Paul L. Bollyky, Jessica C. Sacher
Minyoung Kevin Kim, … , Paul L. Bollyky, Jessica C. Sacher
Published March 3, 2025
Citation Information: J Clin Invest. 2025;135(5):e187996. https://doi.org/10.1172/JCI187996.
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Review

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

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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.

Authors

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

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Figure 1

Development and implementation of phage therapy.

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Development and implementation of phage therapy.
(A) A summary of the ke...
(A) A summary of the key steps in phage therapy development and clinical implementation. The process typically begins with phage identification and selection, including phage bank establishment (sourcing, storage, and characterization of phages), followed by susceptibility testing (using spot tests, plaque assays, efficiency of plating [EOP] assays, and growth kinetics studies). The manufacturing phase involves phage propagation (using selected bacterial strains in liquid- or solid-based systems) and rigorous purification with quality control measures (including endotoxin removal and standardized quality protocols). The therapeutic administration phase encompasses clinical applications (considering various administration routes and dosing strategies) and therapeutic monitoring (tracking treatment efficacy, patient response, and monitoring for potential resistance development and adverse events). Note that these steps are not universally applied in all phage therapies. (B) Phage therapy approaches can be personalized to individual patients (patient-specific phage preparation), fixed (preformulated), or administered as a hybrid of the two approaches. The hybrid model represents an intermediate approach combining elements of both personalized and fixed phage therapy strategies.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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