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.

Description

CROSS REFERENCE TO RELATED APPLICATIONS AND CLAIMS TO PRIORITY[0001]This application is based on U.S. Provisional Patent Application Ser. No. 62 / 082,925, filed Nov. 21, 2014, and U.S. Provisional Patent Application Ser. No. 62 / 133,058, filed Mar. 13, 2015, which applications are incorporated herein by reference in their entireties and to which priority is claimed.FIELD OF THE INVENTION[0002]The present invention relates to methods for preventing or treating Clostridium difficile associated disease (CDAD), and in particular methods and compositions for treating CDAD by administering a therapeutically effective amount of clofazimine or analogues thereof, either alone or in combination with one or more additional therapeutic agents.BACKGROUND OF THE INVENTION[0003]Clostridium difficile (CD) is a Gram positive, spore-forming, anaerobic bacillus recognized to cause diarrhea, pseudomembraneous colitis, toxic megacolon, other gastrointestinal conditions, and even death (Hedge, D. et al. (2...

AI Technical Summary

Benefits of technology

The present invention is about a new method for treating infections caused by the bacteria Clostridium difficile (CDI) and CDAD using a combination of two antimicrobial agents, namely, clofazimine or a clofazimine analogue, and another antimicrobial agent such as vancomycin, metronidazole, or fidaxomicin. The method involves administering the antimicrobial agents to a patient either orally or through injection. The combination of antimicrobial agents can kill or reduce the population of C. difficile in the patient's body. The invention also includes a pharmaceutical composition containing a therapeutically effective amount of clofazimine or a clofazimine analogue and a pharmaceutically acceptable carrier or excipient. The invention can help treat CDI and CDAD infections more effectively than either antimicrobial agent alone.

Problems solved by technology

Unfortunately, exposure to common antibiotic regimens (e.g., cephalosporins, penicillins and fluoroquinolones) in the course of medical treatment of infectious and other diseases (e.g., such as bowel surgery and / or cancer chemotherapy) disrupts the natural gut flora, allowing CD resistant to such antibiotics to colonize and overpopulate in the gut of some patients, particularly elderly patients.

Distension of the colon may result in toxic megacolon.

In addition, even cases of relatively mild CDI may rapidly progress to fulminant CDI, with such patients suffering systemic toxicity (e.g., leukocytosis, hypotension, renal failure, respiratory distress, or even death).

As such, CD infections (CDIs) are increasing worldwide and have become more severe and refractory to treatment in the past decade.

Effective treatment of CDI has proven to be quite challenging due to the need for selective eradication of CD without affecting the normal gut flora.

After each episode or infection, the risk of recurrence of CDI generally increases.

Moreover, use of VAN and FDX is relatively limited, particularly for treating the first episode of CDI, due to their relatively high cost (e.g., current cost is about $2000 per treatment).

However, FDX exhibits no improvement in recurrence rates in patients infected with hypervirulent strains of CD (Louie, T. J. et al.

As such, conventional FDX therapies have not proven to be effective for patients that have suffered multiple CDI relapses.

However, such non-antibiotic based treatments have exhibited mixed results with less efficacy as compared to conventional microbial agents.

However, due to the exorbitant costs involved in the discovery and development of new agents, many pharmaceutical companies are reluctant to invest in new drug discoveries.

Moreover, the return on investment for drug companies on short duration therapeutics like antimicrobial agents is not alluring compared to long duration or life-long therapies.

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