FRANKFURT. Recurrent urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are becoming increasingly difficult to treat due to rising antibiotic resistance. An international research consortium coordinated by Universitätsmedizin Frankfurt is now pursuing a new approach. The project REPhRAME, led by Prof. Dr. Maria J.G.T. Vehreschild, has been awarded €15 million through the European research and innovation program Horizon Europe.

For the first time, a two-step therapeutic approach will be assessed in a randomized clinical trial. First, phages – viruses that specifically kill bacteria – will be used to combat the pathogens. This will be followed by restoration of the intestinal microbiome to prevent recurrent infections. The project began in June 2026 and is planned to run for five years.

Each year, more than 400 million people worldwide develop a urinary tract infection, and in 30 to 50 percent of cases the infection recurs. Since standard antibiotic treatment increases the risk of resistance, many patients find themselves trapped in a cycle of infection, antibiotic treatment, and reinfection, with no lasting solution.

“Phage therapy is one of the most promising responses to the growing challenge posed by multidrug-resistant pathogens. The fact that Universitätsmedizin Frankfurt is leading this international consortium under the direction of Professor Vehreschild once again demonstrates our institution’s outstanding role in translational infection research. I am confident that REPhRAME will significantly advance the clinical use of phage-based therapies—for the direct benefit of our patients,” explains Prof. Dr. Jürgen Graf, Medical Director and Chief Executive Officer of Universitätsmedizin Frankfurt.

Prof. Dr. Enrico Schleiff, President of Goethe University, says: “By developing new therapies against bacterial pathogens, we are continuing the legacy of Paul Ehrlich, who discovered the first antibiotic in Frankfurt and thereby initiated medicine’s successful fight against infectious diseases. Yet biology never stands still, and in the face of increasing bacterial resistance, Goethe University is vigorously pursuing new holistic treatment concepts. REPhRAME is an excellent example of this strategy and makes a significant contribution to strengthening Goethe University’s research profile area Science for Health.”

A New Strategy to Break the Cycle of Infection and Antibiotic Use

REPhRAME relies on phages because, unlike antibiotics, they act with a high degree of specificity: they attack only the target bacteria while leaving much of the natural microbiota unharmed.

The first treatment step uses SNIPR001, a phage cocktail developed using CRISPR gene-editing technology. It specifically targets the most common causes of urinary tract infections—certain strains of the intestinal bacterium Escherichia coli—while reducing the likelihood of new resistance emerging.

The second step focuses on restoring the gut microbiome. INTESTIFIX 001, a product of the Cologne Microbiota Bank, transfers stool bacteria from healthy donors to help re-establish the natural balance of the intestinal microbiota. The goal is to provide long-term protection against recurrent infections.

Clinical Trial Aims to Pave the Way for Phage Therapy in Europe

At the heart of the project is a multicenter clinical trial across Europe that will systematically evaluate the safety and effectiveness of the new treatment. Three approaches will be compared: phage therapy alone, phage therapy combined with antibiotics, and phage therapy followed by microbiome restoration

“Recurrent urinary tract infections place a substantial burden on patients and healthcare systems, yet existing treatment options are simply insufficient for many affected individuals,” says Prof. Dr. Maria J.G.T. Vehreschild, Head of Infectious Diseases at Universitätsmedizin Frankfurt and overall coordinator of the project. “REPhRAME aims to transform phage therapy from a promising research concept into a clinically validated treatment option—with robust data on safety, efficacy, and implementation. In doing so, we hope to lay the foundation for integrating phage therapy into routine medical practice across Europe.”

Frankfurt Coordinates an International Consortium

Led by Universitätsmedizin Frankfurt, the consortium brings together 16 partners from academia, clinical research, and industry across eight European countries. Together, they combine expertise in infectious diseases, clinical trials, phage therapy, microbiome research, microbiology, bioinformatics, regulatory science, drug development, and patient-centered research.

The partners include:

SNIPR Biome (Denmark)
Fraunhofer-Gesellschaft (Germany)
German Center for Infection Research (Germany)
Hannover Medical School (Germany)
LINQ management GmbH (Germany)
University Hospital Cologne (Germany)
HUN-REN Biological Research Centre (Hungary)
Riga Stradiņš University (Latvia)
Leiden University Medical Center (Netherlands)
Jafral (Slovenia)
Swiss Institute of Bioinformatics (Switzerland)
University of Bern (Switzerland)
University of Zurich (Switzerland)
University of Leicester (United Kingdom)
University of Reading (United Kingdom)



Research Beyond the Clinical Trial

REPhRAME also includes a series of accompanying studies. These will examine how phages function and are broken down in the body, what immune responses they trigger, and how the microbiome changes throughout treatment.

In addition, the project will develop AI-based models to predict which patients are most likely to benefit from the therapy. Planned activities also include health-economic analyses and a systematic assessment of the patient perspective, including symptoms, quality of life, and acceptance of the new treatment.

About REPhRAME

REPhRAME stands for “Recurrent Urinary Tract Infection: Efficacy and Safety of Phage Therapy and Microbiota Transfer”. The project is funded by Horizon Europe. It has the potential to significantly reduce antibiotic use, lower the number of recurrent infections, and sustainably improve the quality of life of many patients. At the same time, REPhRAME will establish the scientific and regulatory foundations needed to bring phage-based therapies more broadly into clinical practice in the future.

Founded in 1914, Universitätsmedizin Frankfurt is one of Germany’s leading academic medical centers. It provides patient care through 33 clinics and clinical institutes. Its close integration with scientific research—through more than 20 research institutes operated by the medical faculty and university hospital—ensures that new discoveries are rapidly translated into diagnostic and therapeutic practice.
The institution has around 1,300 inpatient and day-care beds and employs more than 8,500 staff members. Each year, approximately 46,000 inpatients and over 480,000 outpatients receive treatment. Universitätsmedizin Frankfurt is particularly recognized for its interdisciplinary expertise in neuroscience, oncology, and cardiovascular medicine. It also serves as a major center for organ and bone marrow transplantation, dialysis, cardiac surgery, and neurosurgery. Its liver center is the only liver transplantation facility in the German state of Hesse. Additional unique regional responsibilities include oral and maxillofacial surgery, dermatology, and child and adolescent psychiatry for the Frankfurt–Offenbach region. https://www.unimedizin-ffm.de/

Goethe University Frankfurt is a cosmopolitan workshop of the future based in the heart of Europe. Founded in 1914 by Frankfurt citizens, it resumed this tradition as a foundation university in 2008: as an autonomous citizens' university embedded in urban society, both ensuring and offering a high degree of social participation in and support for metropolitan life. With more than 40,000 students, Goethe University Frankfurt is one of Germany’s largest and most research-intensive universities and one of Frankfurt’s largest employers.
As an internationally oriented comprehensive university, Goethe University Frankfurt’s excellent research is clustered along six interdisciplinary, interdepartmental profile areas as well as the diversity of its faculties and subjects, spanning the humanities, social sciences, natural sciences, life sciences and medicine. Together with TU Darmstadt and the University of Mainz, it makes up the Rhine-Main Universities (RMU, https://www.rhein-main-universitaeten.de/en) alliance, and is also a member of the "German U15", the association of the 15 most research-intensive German universities. Goethe University Frankfurt is the only university in the “Frankfurt Alliance” network, whose 15 other members consist of non-university research institutions in the Rhine-Main region. https://www.uni-frankfurt.de/en

Disclaimer: Funded by the European Union. The views and opinions expressed, however, are those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor HADEA can be held responsible for them.