INVESTIGATION OF EFFECT OF CLOFAZIMINE ON TOXIN PRODUCTION OF CLOSTRIDIUM DIFFICILE STRAINS

Clostridioles difficile is a ubiquitous anaerobic gram-positive bacterium that is responsible for severe gastrointestinal diseases. Lack of drugs for relapse of C. difficile infections (CDI) and emergence of strains that produce virulent toxins and spores establish an urgent need for an alternative treatment for CDI. KTI explored the potential of Clofazimine, an FDA approved drug for leprosy, for treatment of CDI due to its antimicrobial activity and low propensity to develop resistance. In the current study we study the effect of i) sub-inhibitory drug concentration of clofazimine on toxin levels of C. Difficile, ii) probiotics on C. difficile, and iii) combination of probiotics and clofazimine. Clofazimine is successful in reducing toxin levels of C. difficile at growth-inhibitory and bactericidal concentrations. We also see a direct correlation between toxin levels and the growth kinetics of the bacteria. Probiotic does not affect the growth of the bacteria as well as the toxin levels of the bacteria. CFZ is also successful in specific killing of C. difficile in presence of bacterial strains of probiotic. In conclusion, CFZ shows excellent in-vitro activity in reduction of toxin levels of C. difficile