Broad-spectrum antimicrobial activity of a ruthenium(II) polypyridyl complex against multidrug-resistant uropathogens and biofilms

Antimicrobial resistance and biofilm persistence are major barriers to treating device-associated infections, including catheter-associated urinary tract infections. We evaluated KLS-116, a ruthenium(II) polypyridyl complex, as a next-generation antimicrobial with broad activity against multidrug-resistant uropathogens. KLS-116 showed potent bactericidal effects under physiologically relevant conditions, with minimum inhibitory concentrations ≤ 25 μM (41.8 mg/L) across diverse species. Checkerboard assays demonstrated compatibility with standard antibiotics, yielding indifferent or additive interactions and no antagonism. Importantly, KLS-116 reduced mature biofilms in continuous-flow catheter models and in static models achieved complete clearance at ≥16× MIC after 24 h, outperforming colistin with prolonged exposure. Over 42 days, resistance evolution showed minimal sensitivity shifts, contrasting with rapid ciprofloxacin resistance, indicating a low propensity for resistance. Activity varied with pH, suggesting that the metabolic state influences efficacy. These results position KLS-116 as a promising candidate for CAUTI management and other biofilm-driven infections, guiding future delivery optimization and in vivo validation.