Bacteria are becoming increasingly resistant to antibiotics. One alternative is treatment with viruses that exclusively infect bacteria, known as phages. An EU-funded research project led by Universitätsmedizin Frankfurt – in which Balgrist University Hospital is participating as one of the leading clinical partners – is the first to investigate, in randomized clinical trials, the combination of phage therapy and microbiome restoration in the intestine to prevent recurring urinary tract infections.

Recurring urinary tract infections (UTIs) are among the most common bacterial infections worldwide and are becoming increasingly difficult to treat due to increasing antibiotic resistance. An international research consortium, coordinated by Universitätsmedizin Frankfurt will now forge a new path. Balgrist University Hospital is contributing its many years of experience in clinical phage therapy and neuro-urology, while University Hospital Frankfurt and University Hospital Cologne are contributing their expertise in restoring the intestinal microbiome using fecal microbiota transfer. Together, they have developed an innovative two-stage treatment approach, which is now being investigated in a randomized clinical trial for the first time. The REPhRAME project has been awarded €15 million through the European research and innovation program Horizon Europe.

The Neuro-Urology Department at Balgrist University Hospital is a recognized leader in the diagnosis and treatment of neuro-urological disorders. Under the direction of Professor Thomas Kessler, the project is researching innovative treatment approaches for patients with complex bladder dysfunction and recurring urinary tract infections and applying them to clinical practice. Participation in REPhRAME builds on this research work and continu-ally advances it.

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

For the first time, a two-step therapeutic approach will be assessed in a randomised 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 infec-tion, antibiotic treatment, and reinfection, with no lasting solution.

“REPhRAME’s particular strength lies in its ability to bring together complementary areas of expertise. Only close collaboration that transcends disciplines and national borders makes it possible to test this innovative therapeutic approach in a large randomized clinical trial. This will create the scientific basis for new treatment options for recurring urinary tract infections,” says Dr. Lorenz Leitner, senior neuro-urology physician at Balgrist University Hospital. Together with Dr. Shawna McCallin, Leitner heads the Phage Therapy & Research Group at Balgrist University Hospital. McCallin adds: “Phages have the potential to fight bacterial infections in a targeted and precise manner while at the same time reducing the use of antibiotics. REPhRAME marks an important milestone for clinical phage research in Europe: for the first time, we are investigating the combination of phage therapy and intestinal microbiome restoration in a large randomized clinical trial. This unique opportunity brings us a significant step closer to evidence-based use of phage therapy in clinical practice.”

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 a proprietary CRISPR-armed phage cocktail that 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 ther-apy 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 individu-als,” says Prof. Dr. Maria J.G.T. Vehreschild, Head of Infectious Diseases at Universi-tätsmedizin Frankfurt and overall coordinator of the project. “REPhRAME aims to trans-form 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.”

The 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 Hospital Balgrist, University of Zurich (Switzerland), University of Leicester (United Kingdom), University of Reading (United Kingdom).

Contact

PD Dr. Lorenz Leitner
Neuro-Urology
Balgrist University Hospital / University of Zurich
lorenz.leitner@remove-this.balgrist.ch

Balgrist University Hospital, Branding
+41 44 386 14 15 / kommunikation@remove-this.balgrist.ch