VesiX, a bactericidal solution, has been proposed to treat antibiotic-recalcitrant recurrent urinary tract infections (RUTIs) in women considering a cystectomy and urinary diversion as their final option. We report on the in vitro efficacy of VesiX in a limited FDA-approved trial of 3 women.

Following IRB and Emergency IND FDA approval, three eligible post-menopausal women underwent an intravesical treatment with VesiX after completing an antibiotic course.
 
Urine samples were collected prior to VesiX treatment (Pre-VesiX) and just after VesiX treatment (Post-VesiX) and stored immediately on ice. 100L of urine was plated on Chromagar Orientation for colony forming unit (CFU) enumeration. Colonies with distinct morphologies (color) were re-struck on Chromagar Orientation and well-isolated single colonies were grown in BHI broth. The 16S rRNA gene was amplified for each strain and Sanger-sequenced to confirm species identify. Susceptibility to VesiX was tested for the 7 patient isolate strains by bactericidal assay. Overnight cultures of each strain were diluted to OD600=0.05 in BHI broth and grown until mid-log phase (OD600=0.5) at 37C. The bacteria were then treated with VesiX or left untreated for one hour at 37C. CFUs were enumerated in each sample by spot assay to measure the bactericidal effect of VesiX on each strain. E. coli K12 was used as a sensitive control.

Bacteria were present in the urine of all patients prior to VesiX treatment and absent from the urine following VesiX treatment. The primary uropathogens present were E. faecalis in VSX1, E. coli in VSX2 and a co-infection of E. coli, E. faecalis and Staphylococcus in VSX3 where E. faecalis was the most abundant species. The results of the bactericidal assay presented in Figure 1 clearly demonstrate that the formulation of VesiX used in the trial is bactericidal against the bacteria isolated from the urine of the patients prior to VesiX treatment. Furthermore, it is effective against both Gram-negative (E. coli) and Gram-positive (E. faecalis) uropathogens. Of the 3 patients in the study followed up to one year after the VesiX treatment, one remained infection free, one had a few UTI episodes but with easier strains to treat with a lesser resistance profile, and one failed.

Few intravesical solutions are available for treatment of antibiotic-recalcitrant RUTIs. In this emergency FDA approved VesiX therapy, three women were treated at a very advanced stage of RUTI, with only one IV antibiotic class left and contemplating a cystectomy. Their very encouraging clinical results as well as the ex-vivo effect of VesiX over a range of pathogenic strains suggest a role for such a therapy directly addressing the cystitis changes noted over the lining of these bladders.

A preliminary trial of intravesical VESIX indicates a very efficient clinical and ex-vivo performance against a variety of uropathogens. Vesix can be tested ex vivo for its efficacy before use.