Methods and Compositions for Treating Clostridium difficile Associated Disease

Abstract

Methods for treating a subject infected with Clostridium difficile comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of clofazimine and/or a clofazimine analogue. Pharmaceutical compositions comprising clofazimine and/or an analogue(s) thereof, and optionally one or more additional therapeutic agents, are provided for treating Clostridium difficile infection and diseases or symptoms associated therewith.

What is claimed is: 
     
         1 . A method of treating a subject infected with  Clostridium difficile  comprising administering to said subject a therapeutically effective amount of clofazimine or a clofazimine analogue. 
     
     
         2 . The method of  claim 1 , wherein said clofazimine analogue is 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. 
     
     
         3 . The method of  claim 2 , wherein said clofazimine analogue is B4129 analogue, B4157 analogue, or B746 analogue. 
     
     
         4 . The method of  claim 1 , wherein said compound is administered orally. 
     
     
         5 . The method of  claim 1 , wherein said compound is administered in a concentration from about 0.020 μg/ml to about 1.0 μg/ml for in vitro conditions. 
     
     
         6 . The method of  claim 5 , wherein said compound is administered in a concentration from about 0.031 μg/ml to about 0.25 μg/ml for in vitro conditions. 
     
     
         7 . The method of  claim 1 , wherein said compound is administered in combination with at least one additional therapeutic agent. 
     
     
         8 . The method of  claim 7 , wherein said additional therapeutic agent is an antimicrobial agent. 
     
     
         9 . The method of  claim 8 , wherein said additional therapeutic agent is selected from the group consisting of vancomycin, metronidazole, and fidaxomicin. 
     
     
         10 . A method of treating a subject infected with a population of  Clostridium difficile  comprising administering to said subject a pharmaceutical composition comprising:
 (A) an effective amount of a first antimicrobial agent comprising clofazimine or a clofazimine analogue;   (B) an effective amount of a second antimicrobial agent; and   (C) a pharmaceutically acceptable carrier or excipient;   
       and wherein said effective amounts of said first and second antimicrobial agents cause said pharmaceutical composition to mediate a synergistically increased reduction in said population of  Clostridium difficile  relative to the reductions in said population mediated by:
 (1) a pharmaceutical composition comprising said effective amount of said first antimicrobial agent but lacking said effective amount of said second antimicrobial agent; and 
 (2) a pharmaceutical composition comprising said effective amount of said second antimicrobial agent but lacking said effective amount of said first antimicrobial agent. 
 
     
     
         11 . The method of  claim 10 , wherein said clofazimine analogue is 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. 
     
     
         12 . The method of  claim 11 , wherein said clofazimine analogue is B4129 analogue, B4157 analogue, or B746 analogue. 
     
     
         13 . The method of  claim 10 , wherein said first antimicrobial agent is administered in a concentration from about 0.020 μg/ml to about 1.0 μg/ml for in vitro conditions. 
     
     
         14 . The method of  claim 10 , wherein said first antimicrobial agent is administered in a concentration from about 0.031 μg/ml to about 0.25 μg/ml for in vitro conditions. 
     
     
         15 . The method of  claim 10 , wherein said second antimicrobial agent is selected from the group consisting of vancomycin, metronidazole, and fidaxomicin. 
     
     
         16 . A pharmaceutical composition for killing or reducing a population of  Clostridium difficile  comprising a therapeutically effective amount of clofazimine or a clofazimine analogue, and a pharmaceutically acceptable carrier or excipient. 
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein said clofazimine analogue is 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. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein said clofazimine analogue is B4129 analogue, B4157 analogue, or B746 analogue. 
     
     
         19 . The pharmaceutical composition of  claim 16 , further comprising at least one additional therapeutic agent. 
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein said additional therapeutic agent is an antimicrobial, an antibiotic, or a lytic enzyme. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein said additional therapeutic agent is a antimicrobial agent selected from the group consisting of vancomycin, metronidazole, and fidaxomicin.