Phage Therapy at the Crossroads Between Clinical Promise and Regulatory Challenge

噬菌体疗法正处于临床前景与监管挑战的十字路口

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Abstract

Bacteriophage (phage) therapy, including monophage preparations, phage cocktails, engineered phages, and phage-derived enzymes, has re-emerged as a potential option for difficult-to-treat and biofilm-associated infections in the context of rising antimicrobial resistance. Recent scientific and regulatory developments, such as the 2024 World Health Organization Bacterial Priority Pathogens List and the introduction of the European Pharmacopoeia general chapter 5.31 on phage therapy medicinal products, highlight the growing interest in establishing quality, safety, and governance standards for clinical implementation. This narrative review provides an overview of current clinical applications of phage therapy, drawing on published case reports, case series, early-phase clinical studies, and regulatory experiences across different healthcare settings. Clinical use has been reported in respiratory, urinary tract, musculoskeletal, cardiovascular, and device-associated infections, particularly in cases involving multidrug-resistant pathogens, often in combination with antibiotics. At the same time, the biological characteristics of phages, such as strain specificity, adaptive composition of phage cocktails, and the need for individualized formulations, pose significant regulatory and translational challenges. Access to phage therapy currently relies on heterogeneous regulatory mechanisms, including compassionate use programmes, magistral preparations, named-patient pathways, and other national frameworks. Overall, phage therapy represents a promising strategy for selected infections, but its broader clinical adoption will depend on harmonized regulatory approaches, robust quality standards, and the generation of stronger clinical evidence to support safe and scalable use.

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