Modelling Phage Therapy forUrinary and Bloodstream Infections: The Effects of Phage Cocktails on Catheter Biofilms, and a High-Throughput Analysis of Phage-Antibiotic Interactions

<p dir="ltr">The emergence of antibiotic-resistant bacteria has become a growing concern in healthcare, prompting the search for alternative treatments. Bacteriophages, viruses that infect bacteria, are one such alternative. However, research on phage therapy predominantly focuses on in vitro studies or clinical case reports, with limited understanding of the translational intersection between these two stages. This study aims to investigate two critical yet underexplored aspects of phage therapy: the interactions between phages and commonly prescribed antibiotics, and the effectiveness of a standardized phage cocktail in treating ex vivo catheter samples from patients with long-term polymicrobial infections. By focusing on Escherichia coli and Klebsiella pneumoniae – the most common causes of urinary tract infections (UTIs) and bloodstream infections (BSIs) – this study targets a major clinical challenge.</p><p dir="ltr">The largest-scale phage-antibiotic interaction study to date was conducted by testing a collection of phages alongside various antibiotics against bacterial strains isolated from patients with UTIs/BSIs. While combinations resulted in effects ranging from additive to antagonistic, a distinct pattern was observed in E. coli with β-lactam antibiotics and the Tequatrovirus genus, which displayed significant additivity – a correlation deserving of further investigation.</p><p dir="ltr">Catheters collected from patients with UTIs were treated with a phage cocktail to determine whether a 3-phage cocktail, developed on in vitro assays, will be sufficient to treat a wide variety of bacterial strains. The catheters were treated in an Artificial Urinary Tract for 5 days and then sent for CT-scanning; the results demonstrate marked reduction of biofilm in both thickness and volume, up to 99.99%, demonstrating the efficiency of the phage cocktail against otherwise unknown strains.</p>