Investigational new treatments for Clostridium difficile infection

•Two drugs have been FDA-approved for Clostridium difficile infection in the past 30 years.•Thirteen treatments are currently in clinical development.•The treatments in development are striking in the diversity of targeting strategies employed.•Incidence continues to rise and to spread outside the USA and Europe.•Regulatory incentives should also be made outside the USA to continue to encourage innovation. Significant progress has been made by industry and academia in the past two years to address the medical threats posed by Clostridium difficile infection. These developments provide an excellent example of how patient need has driven a surge of innovation in drug discovery. Indeed, only two drugs were approved for the infection in the past 30 years but there are 13 treatment candidates in clinical trials today. What makes the latter number even more remarkable is the diversity in the strategies represented (antibiotics, microbiota supplements, vaccines, antibiotic quenchers and passive immunization). In this review, we provide a snapshot of the current stage of these breakthroughs and argue that there is still room for further innovation in treating C. difficile infection.