Evaluation of phage-antibiotic combinations in the inactivation of urinary tract infection-related bacteria.

AIMS: To evaluate the efficacy of bacteriophage-antibiotic combination therapy against major urinary tract infection (UTI) pathogens and determine whether combining phages with ciprofloxacin enhances bacterial killing, delays resistance emergence, and improves treatment performance under physiologically relevant conditions. MATERIALS AND METHODS: Five clinically relevant UTI pathogens were tested: Escherichia coli (UPEC), Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis. Phages from a commercially available cocktail were screened and supplemented with a lab-isolated phage to improve E. coli coverage. In vitro assays evaluated bacterial inactivation using phages alone and in combination with ciprofloxacin at varying concentrations, including sub-MIC levels. Resistance emergence and associated fitness costs were assessed. Ex vivo efficacy was further tested using filtered human urine to simulate physiologically relevant conditions. RESULTS: Phage-antibiotic combinations significantly enhanced bacterial inactivation across all tested species compared to monotherapies, including at sub-MIC ciprofloxacin concentrations. Combination treatments delayed resistance development and imposed fitness costs on resistant E. coli mutants. Ex vivo urine assays confirmed that phages remained effective in physiologically relevant conditions, particularly in combination regimens, despite reduced antibiotic efficacy in urine. CONCLUSIONS: Phage-antibiotic combination therapy improves bacterial killing, suppresses resistance emergence, and remains effective in urine-based models. These findings support integrating phage therapy with conventional antibiotics as a promising strategy for UTI management.