Preclinical Evaluation of Nitroxide-Functionalised Ciprofloxacin as a Novel Antibiofilm Drug Hybrid for Urinary Tract Infections

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates and can involve biofilm formation on patient catheters. Biofilms inherently tolerant to antimicrobials, making them difficult eradicate. Many antibiofilm agents alone do not have bactericidal activity; therefore, linking antibiotics is a promising strategy. However, many of these hybrid been tested in relevant preclinical settings, limiting their potential for clinical translation. Here, we evaluate ciprofloxacin di-nitroxide (CDN11), previously reported activity against uropathogenic Escherichia coli (UPEC) strain UTI89 vitro, as UTI therapeutic using multiple models that reflect various aspects pathogenesis. We report improved vitro over parent drug mature biofilms formed inside polyethylene In bladder cell monolayers infected UTI89, treatment CDN11 afforded significant reduction titers, including intracellular UPEC. Infected mouse bladders containing biofilm-like reservoirs UPEC showed decreased loads after ex vivo CDN11. Activity was across different UTI, showcasing nitroxide–antibiotic hybridization approach. The pipeline described here could be readily used testing other new compounds, fast-tracking development novel therapeutics.