Pharmaceutical compositions comprising clofazimine analog compound b746 or clofazimine analog compound b826

Abstract

Methods for treating a subject infected with Clostridium difficile comprises administering to the subject a synergistic combination of clofazimine and metronidazole. Pharmaceutical compositions comprising clofazimine and metronidazole are provided for treating Clostridium difficile infection and diseases or symptoms associated therewith.

We claim: 
     
         1 . A method of inhibiting the activity of  Clostridium difficile  in a subject, comprising administering to the subject a pharmaceutical composition consisting of a clofazimine analogue selected from the group consisting of B4154 analogue, B4129 analogue, B4087 analogue, B4165 analogue, B826 analogue, B3640 analogue, B4100 analogue, B4101 analogue, B4021 analogue, B4157 analogue, B746 analogue, and B3987 analogue; and at least one pharmaceutically acceptable excipient. 
     
     
         2 . The method of  claim 1 , wherein said pharmaceutical composition is administered orally. 
     
     
         3 . The method of  claim 1 , wherein said compound is administered in a concentration from about 0.31 μg/ml to about 1.0 μg/ml for in vitro conditions. 
     
     
         4 . The method of  claim 3 , wherein said compound is administered in a concentration from about 0.062 μg/ml to about 0.25 μg/ml for in vitro conditions. 
     
     
         5 . The method of  claim 1 , wherein said method further comprises administering at least one additional antimicrobial agent. 
     
     
         6 . The method of  claim 5 , wherein said antimicrobial agent is azaquinone, metronidazole, vancomycin, or fidaxomicin. 
     
     
         7 . The method of  claim 5 , wherein the administration of the at least one additional antimicrobial agent is concurrent. 
     
     
         8 . The method of  claim 5 , wherein the administration of the at least one additional antimicrobial agent is sequential. 
     
     
         9 . The method of  claim 1 , wherein the clofazimine analogue is B4129 analogue, B4157 analogue, or B746 analogue. 
     
     
         10 . A method of treating  Clostridium difficile  associated disease or  Clostridium difficile  infection in a subject, comprising administering to the subject a pharmaceutical composition consisting of a clofazimine analogue, at least one pharmaceutically acceptable excipient, and at least one additional antimicrobial agent; wherein the clofazimine analogue is B4154 analogue, B4129 analogue, B4087 analogue, B4165 analogue, B826 analogue, B3640 analogue, B4100 analogue, B4101 analogue, B4021 analogue, B4157 analogue, B746 analogue, or B3987 analogue. 
     
     
         11 . The method of  claim 10 , wherein the clofazimine analogue is B4129 analogue, B4157 analogue, or B746 analogue. 
     
     
         12 . The method of  claim 10 , wherein the antimicrobial agent is azaquinone, fidaxomicin, metronidazole, or vancomycin.