Methods and compositions for the treatment of shiga toxicosis

Abstract

Methods for treating Shiga toxicosis, caused by infection with Shiga toxin bacteria, are provided. The methods include administering to a subject in need thereof an effective amount of one or more active agents selected from tamoxifen, 4-hydroxytamoxifen, endoxifen, toremifene, raloxifene, bazedoxifene, and pharmaceutically acceptable salts thereof. In some embodiments, the methods further include the administration of an antibiotic or a manganese compound to the subject. Pharmaceutical compositions for the treatment of Shiga toxicosis are also described.

What is claimed is: 
     
         1 . A pharmaceutical composition comprising: (i) tamoxifen, 4-hydroxytamoxifen, endoxifen, toremifene, raloxifene, bazedoxifene, or a combination thereof; (ii) a manganese compound, an antibiotic, or a combination thereof; and (iii) one or more pharmaceutically acceptable excipients. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the manganese compound is a manganese salt. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the manganese salt is selected from the group consisting of manganese chloride, manganese borate, manganese nitrate, manganese phosphate, manganese sulfate, and combinations thereof. 
     
     
         4 . The pharmaceutical composition of  claim 2 , wherein the manganese salt is selected from the group consisting of manganese carbonate, manganese acetate, manganese citrate, manganese oleate, manganese oxalate, and combinations thereof. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the manganese compound is a manganese amino acid chelate. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the manganese amino acid chelate includes one or more of arginine, asparagine, cysteine, glutamine, histidine, lysine, ornithine, and tryptophan. 
     
     
         7 . The pharmaceutical composition of  claim 1 , which comprises: (i) tamoxifen, toremifene, raloxifene, or a combination thereof; and (ii) manganese chloride, manganese sulfate, or a combination thereof. 
     
     
         8 . The pharmaceutical composition of  claim 7 , which comprises tamoxifen and manganese chloride or manganese sulfate. 
     
     
         9 . The pharmaceutical composition of  claim 7 , further comprising an antibiotic. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the antibiotic is a quinolone, a β-lactam, a macrolide, an aminoglycosides, a monobactam, a carbapenem, a thiazolide, a tetracycline, a lincosamide, a sulfonamide, a nitroimidazole, or a combination thereof. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the antibiotic is a quinolone, a β-lactam, a macrolide, an aminoglycosides, a monobactam, a carbapenem, a thiazolide, a tetracycline, a lincosamide, a sulfonamide, a nitroimidazole, or a combination thereof. 
     
     
         12 . The pharmaceutical composition of  claim 1 , which is formulated for oral administration, intravenous administration, intramuscular administration, intraperitoneal administration, subcutaneous administration, intrathecal administration, intraarterial administration, nasal administration, or rectal administration.