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Sanchez BC, Heckmann ER, Green SI, Clark JR, Kaplan HB, Ramig RF, Hines-Munson C, Skelton F, Trautner BW, Maresso AW. Development of Phage Cocktails to Treat Catheter-Associated Urinary Tract Infection and Associated Biofilms. Frontiers in microbiology. 2022 May 10; 13:796132.
High rates of antimicrobial resistance and formation of biofilms makes treatment of catheter-associated urinary tract infections (CAUTI) particularly challenging. CAUTI affect 1 million patients per year in the United States and are associated with morbidity and mortality, particularly as an etiology for sepsis. Phage have been proposed as a potential therapeutic option. Here, we report the development of phage cocktails that lyse contemporary strains isolated from the urine of patients with spinal cord injury (SCI) and display strong biofilm-forming properties. We characterized phage against biofilms in two CAUTI models. Biofilm viability was measured by an MTT assay that determines cell metabolic activity and by quantification of colony forming units. Nine phage decreased cell viability by > 80% when added individually to biofilms of two strains in human urine. A phage cocktail comprising six phage lyses 82% of the strains in our library and is highly effective against young and old biofilms and against biofilms on silicon catheter materials. Using antibiotics together with our phage cocktail prevented or decreased emergence of resistant to phage in human urine. We created an anti-biofilm phage cocktail with broad host range against strains isolated from urine. These phage cocktails may have therapeutic potential against CAUTI.