Preclinical Evaluation of Pharmaceutical Compositions and Their Components for Urinary Health

Abstract

Background: The need for products that treat or prevent urinary tract infections without resort to antibiotics that may select for resistant bacterial strains has created a need to develop antibiotic-free therapeutics. Objective: To conduct an exploratory evaluation of intrinsic antimicrobial activity of a panel of compounds alone or in combination against urinary pathogens and probiotic organisms as well as their effect on biofilm formation and immune activity in infected cultured bladder epithelial cells. Results: Of the compounds tested, 1% citric acid was most consistently inhibitory to urinary pathogens as were combinations containing citric acid. Two combinations of compounds were tested and both showed antimicrobial activity when challenged with 1 × 105 bacteria/mL. The two combination products and D-mannose did not inhibit probiotic microorganisms and one composition increased the inhibitory potential of probiotic organisms. Results obtained with biofilm studies were variable, but probiotic biofilm was enhanced under some circumstances. Biofilms of some urinary pathogens were reduced by antimicrobial mixtures. A strong cytokine response was elicited when T24 bladder epithelial cells were infected for one hour with urinary pathogens and a modest reduction in cytokine response was recorded with some combinations of test compounds. Conclusion: Citric acid alone and mixtures of various compositions containing citric acid inhibited the growth and biofilm formation by 4 uropathogens. Probiotic organisms grew in the presence of mannose and citric acid-containing combinations. One of the combinations enhanced probiotic activity of Lactobacilli against uropathogens. When infecting T24 cell monolayers with uropathogens, potential modulation of inflammatory activity was demonstrated.