The European Union has awarded 15 million euro under its Horizon Europe research and innovation program to launch REPhRAME, an ambitious international project aimed at developing a new treatment strategy for recurrent urinary tract infections (UTIs). Coordinated by Universitätsmedizin Frankfurt under the leadership of Prof. Dr. Maria J.G.T. Vehreschild, the five-year project will evaluate phage therapy as a potential alternative to antibiotics in patients suffering from recurrent bacterial infections.
Urinary tract infections are among the world's most common bacterial infections, affecting more than 400 million people annually. Around 30–50% of patients experience recurrent infections, often leading to repeated antibiotic use. This cycle contributes to the growing problem of antimicrobial resistance (AMR), making infections increasingly difficult to treat.
The REPhRAME project introduces a novel two-step treatment strategy designed to break this cycle. In the first phase, patients will receive SNIPR001, a CRISPR-engineered phage cocktail that specifically targets disease-causing strains of Escherichia coli (E. coli), the bacteria responsible for most urinary tract infections. Unlike conventional antibiotics, bacteriophages selectively destroy harmful bacteria while preserving beneficial microorganisms in the body.
The second phase focuses on restoring the gut microbiome using INTESTIFIX 001, a microbiota transfer therapy developed by the Cologne Microbiota Bank. The treatment transfers beneficial bacteria from healthy donors to rebuild the natural intestinal microbiome, reducing the likelihood of future infections.
At the core of the project is a large multicenter randomized clinical trial involving hospitals across Europe. Researchers will compare three treatment strategies: phage therapy alone, phage therapy combined with antibiotics, and phage therapy followed by microbiome restoration. The study aims to generate robust evidence on the safety, effectiveness, and practical implementation of phage-based treatments.
According to Prof. Dr. Maria J.G.T. Vehreschild, recurrent UTIs place a significant burden on both patients and healthcare systems, while existing treatment options remain inadequate for many individuals. She noted that REPhRAME seeks to transform phage therapy from an experimental concept into a clinically validated treatment that could eventually become part of routine medical practice across Europe.
The consortium consists of 16 academic, clinical, and industry partners from eight European countries, bringing together expertise in infectious diseases, microbiology, microbiome research, bioinformatics, clinical trials, regulatory science, and pharmaceutical development.
Beyond the clinical trial, the project will investigate how bacteriophages behave inside the human body, how they interact with the immune system, and how microbiome composition changes during treatment. Researchers will also develop artificial intelligence (AI)-based prediction models to identify patients most likely to benefit from phage therapy. Additional studies will assess patient quality of life, treatment acceptance, and the economic impact of reducing antibiotic use.
If successful, REPhRAME could pave the way for integrating phage therapy into mainstream clinical practice, offering a promising new solution to recurrent bacterial infections while helping reduce antibiotic resistance—a growing global public health challenge.
