1447. Ex Vivo Human Bladder Tissue Model to Evaluate Lactobacillus-Containing Formulations as Preventative Treatment Against Common Urogenital Pathogens

Abstract

BackgroundUrinary tract infections (UTIs) are common bacterial infections in adults, and catheter-associated UTIs are the most common nosocomial infection. The rise of multidrug-resistant organisms and an increased focus on antibiotic stewardship has influenced the development of novel treatments against such infections, and there is growing interest in the use of probiotics for antimicrobial therapy. We used an ex vivo human bladder tissue (HBT) model to evaluate the antimicrobial efficacy and biocompatibility of lactobacillus-based developmental formulations (created and supplied by ICET, Inc.) for preventative treatment against common UTI pathogens.MethodsTo assess antimicrobial efficacy, lactobacillus-based formulations (live and attenuated) were spiked with five prevalent UTI organisms (5 × 103 CFU/mL). Ex vivo HBT explants were treated with 300 μL of spiked formulation for 6 and 24 h at 37°C, then processed and plated on selective agars. Biocompatibility studies assessed ex vivo HBT tissue viability and inflammatory response (IL-8) to lactobacillus-containing formulations with MTT assay and ELISA at 2 h post-treatment.ResultsAt 6 h, live lactobacillus-containing formulations (29–124, 29-124C) were bacteriostatic (90.00–99.89% log CFU/mL reduction) against Escherichia coli and Klebsiella pneumoniae and bactericidal (≥99.90% log CFU/mL reduction) against Candida albicans, Enterococcus faecalis, and Proteus mirabilis. By 24 h, live formulations were bactericidal against all five organisms tested. Attenuated formulation 29–125 achieved bacteriostatic efficacy against E. coli, K. pneumoniae, and P. mirabilis and bactericidal efficacy against C. albicans and E. faecalis at 24 h. Biocompatibility assessments following 2 h exposure to lactobacillus-based formulations revealed exposed explants were fully viable, with no significant changes in IL-8 production compared with PBS-treated controls.ConclusionThis study suggests lactobacillus-based formulations are effective and safe options for UTI prevention. While this static ex vivo human bladder mucosalmodel does not fully replicate the dynamic and diluting conditions that occur in vivo, we anticipate that our findings will be confirmed by future in vivo studies. Disclosures All authors: No reported disclosures.