Use of ramoplanin to treat diseases associated with the use of antibiotics

Abstract

The invention features a method of treating or preventing a disease associated with the use of antibiotics in a patient in need thereof by administering to the patient ramoplanin in an amount and for a duration effective to treat said disease. The disease may be caused, for example, by the presence of a bacterium such as enterotoxin producing strains of C. difficile, C. perfringens , or S. aureus.

1 . A method of treating a disease caused by a bacterial infection of the colon, said method comprising administering to a patient in need thereof an effective amount of ramoplanin in a pharmaceutical formulation that maintains the integrity of the formulation during passage through the gastrointestinal tract and permits release of said ramoplanin into the colon or other portion of the gastrointestinal tract. 
     
     
         2 . The method of  claim 1 , wherein the bacterial infection is a  Clostridium difficile, Staphylococcus aureus , or  Clostridium perfringens  infection. 
     
     
         3 . The method of  claim 2 , wherein said  Clostridium difficile  is resistant to metronidazole and/or vancomycin. 
     
     
         4 . The method of  claim 1 , further comprising administering to said patient a corticosteroid. 
     
     
         5 . The method of  claim 4 , wherein said corticosteroid is algestone, 6-alphafluoroprednisolone, 6-alpha-methylprednisolone, 6-alpha-methylprednisolone 21 acetate, 6-alpha-methylprednisolone 21-hemisuccinate sodium salt, 6-alpha,9-alphadifluoroprednisolone 21-acetate 17-butyrate, amcinafal, beclomethasone, beclomethasone dipropionate, beclomethasone dipropionate monohydrate, 6-betahydroxycortisol, betamethasone, betamethasone-17-valerate, budesonide, clobetasol, clobetasol propionate, clobetasone, clocortolone, clocortolone pivalate, cortisone, cortisone acetate, cortodoxone, deflazacort, 21-deoxycortisol, deprodone, descinolone, desonide, desoximethasone, dexamethasone, dexamethasone-21-acetate, dichlorisone, diflorasone, diflorasone diacetate, diflucortolone, doxibetasol, fludrocortisone, flumethasone, flumethasone pivalate, flumoxonide, flunisolide, fluocinonide, fluocinolone acetonide, 9-fluorocortisone, fluorohydroxyandrostenedione, fluorometholone, fluorometholone acetate, fluoxymesterone, flupredidene, fluprednisolone, flurandrenolide, formocortal, halcinonide, halometasone, halopredone, hyrcanoside, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone cypionate, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydrocortisone probutate, hydrocortisone valerate, 6-hydroxydexamethasone, isoflupredone, isoflupredone acetate, isoprednidene, meclorisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, paramethasone, paramethasone acetate, prednisolone, prednisolone acetate, prednisolone metasulphobenzoate, prednisolone sodium phosphate, prednisolone tebutate, prednisolone-21-hemisuccinate free acid, prednisolone-21-acetate, prednisolone-21 (beta-D-glucuronide), prednisone, prednylidene, procinonide, tralonide, triamcinolone, triamcinolone acetonide, triamcinolone acetonide 21-palmitate, triamcinolone diacetate, or triamcinolone hexacetonide. 
     
     
         6 . The method of  claim 5 , wherein said corticosteroid is budesonide. 
     
     
         7 . The method of  claim 1 , further comprising administering to said patient one or more compounds selected from detoprofen, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenameate, mefenamic acid, meloxicam, nabumeone, naproxen sodium, oxaprozin, piroxicam, sulindac, tolmetin, celecoxib, rofecoxib, aspirin, choline salicylate, salsalte, cyclosporine, azathioprine, methotrexate, leflunomide, cyclophosphamide, hydroxychloroquine, sulfasalazine, D-penicillamine, minocycline, etanercept, infliximab, sulfasalazine, olsalazine, balsalazide, azathioprine, 6-mercaptopurine, or methotrexate. 
     
     
         8 . The method of  claim 1 , further comprising administering to said patient bismuth, diphenoxylate, atropine, kaolin, pectin, loperamide, or paragoric. 
     
     
         9 . The method of  claim 1 , wherein the disease is antibiotic-associated diarrhea or pseudomembranous colitis. 
     
     
         10 . The method of  claim 1 , wherein said ramoplanin is administered in an amount between 50 mg and 1 g. 
     
     
         11 . The method of  claim 10 , wherein said ramoplanin is administered in an amount between 200 and 400 mg once or twice daily. 
     
     
         12 . The method of  claim 1 , wherein said ramoplanin is administered one to four times daily for three to fifteen days. 
     
     
         13 . The method of  claim 1 , wherein said ramoplanin is administered orally. 
     
     
         14 . The method of  claim 1 , further comprising administering to said patient vancomycin, bacitracin, or metronidazole. 
     
     
         15 . A method for reducing sporulation of  Clostridium difficile  or  Clostridium perfringens  in a patient, said method comprising administering to said patient ramoplanin in an amount and for a duration effective to reduce sporulation of  Clostridium difficile  or  Clostridium perfringens.    
     
     
         16 . The method of  claim 15 , wherein said Clostridium difficile is resistant to metronidazole and/or vancomycin. 
     
     
         17 . The method of  claim 15 , wherein said ramoplanin is administered in an amount between 50 mg and 1 g. 
     
     
         18 . The method of  claim 15 , wherein said ramoplanin is administered in an amount between 200 and 400 mg once or twice daily. 
     
     
         19 . The method of  claim 15 , wherein said ramoplanin is administered one to four times daily for three to fifteen days. 
     
     
         20 . The method of  claim 19 , wherein said ramoplanin is administered orally. 
     
     
         21 . The method of  claim 15 , further comprising administering to said patient vancomycin, bacitracin, or metronidazole.