Therapies on the horizon for Clostridium difficile infections

ABSTRACT

Introduction: Clostridium difficile infections are a leading cause of healthcare facility outbreaks of gastrointestinal illness that may have serious complications and a high rate of recurrent disease. Despite the availability of standard antibiotic treatments, data from national surveillance programs indicate that the incidence of this disease continues to increase, placing a heavy burden on healthcare systems. New emerging strategies are being tested to replace or augment these standard antibiotics.

Areas covered: Thirty-two current investigational agents focusing on different strategies for both prevention and treatment of C. difficile infections are reviewed. Data was gathered from a literature search of public databases for published trials from 1999-November 13, 2015 and from the author’s compendium of knowledge. Agents reviewed included 13 antibiotics, two antibiotic inactivators, seven bacteria or yeasts acting to enhance the normal microbiome, seven immunizing agents and three toxin binders. Of the 32 investigational treatments reviewed, 8 (25%) showed significant efficacy in phase II or III clinical trials and are actively being developed as new therapies for C. difficile infections.

Expert opinion: A number of potential treatments have floundered during their development process, while others have shown promising results. The strongest efficacy has been in the areas of newer antibiotics, probiotics, monoclonal antibodies and vaccines. By targeting the pathogenic pathway of C. difficile infections, multiple strategies for prevention and treatment have been developed.

KEYWORDS:

• Antibiotics
• clostridium difficile
• fecal microbial transplant
• monoclonal antibodies
• novel therapeutics
• prevention
• probiotics
• toxin-binders
• treatments
• vaccines

Article highlights

• Clostridium difficile infections (CDI) are one of the leading causes of gastrointestinal outbreaks at healthcare facilities and affects more than one-half million people in the U.S.A. alone.

• Consequences of CDI may include development of severe colitis, increased mortality and morbidity, longer healthcare stays and increased healthcare costs.

• Current approved treatments for CDI include one of three antibiotics, but nearly 1 in 5 CDI patients suffer at least one recurrence of CDI.

• Prevention of CDI rests on multipronged infection control, educational programs and antibiotic stewardship, but has not been entirely successful.

• Newer investigational strategies have included the development of new antibiotics, agents that inactivate colonic levels of antibiotics, bacterial and yeast strains that interact with the normal protective microbiome, use of toxin binders and immunizing agents.

• Of the 32 investigational treatments reviewed, 8 (25%) showed significant efficacy in phase II or III clinical trials and are being actively studied.This box summarizes key points contained in the article.

Financial and competing interests disclosure

LV McFarland is a paid lecturer for Biocodex and Lallemand and is on the Scientific Advisory Board for BioK+. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.