Evolution of Targeted Therapies for C difficile

Slideshow below. 

Clostridioides difficile (C difficile) is a gram-positive anaerobic bacillus that produces toxins (enterotoxin A [TcdA] and cytotoxin B [TcdB]) that can damage the lining of the gastrointestinal tract and cause potentially life-threatening disease of the large intestine.¹ C difficile infection (CDI) is not only a common nosocomial infection, but an increasing incidence is seen in the community with a high disease burden, as reinfection often occurs.² C difficile is very contagious and spreads easily via contaminated surfaces that act as reservoirs (especially in healthcare settings); the spores of this bacterium are very hard to kill.³

CDI often occurs either while the patient is taking antibiotics or soon after finishing them, as the intestinal (gut) microbiome and metabolism are altered, which allows for C difficile to proliferate.⁴ People with a compromised immune system or other comorbid conditions, or who are older than 65 years of age, are especially prone to CDI.¹

Antibiotics are the first-line treatment for primary and recurrent CDI (rCDI), although they do not always kill the spores,³ and the dysbiosis caused by antibiotics within the gut environment still needs to be addressed.⁴ A humanized monoclonal antibody (an immunoglobulin G against the cytotoxin B), in combination with antibiotics, has been shown to help prevent rCDI in a subset of patients.⁵

Therapies that help restore the gut microbiota to a eubiotic state, especially after antibiotic treatment for C difficile, have been shown to help manage and prevent future rCDI. Experimental fecal microbiota transplantatio (FMT) performed under enforcement discretion from the FDA is one such microbiota restoration therapy.³ Microbes harvested from healthy donor stool are transplanted into the intestine of a recipient (usually via colonoscopy) to help restore the gut microbiome and prevent CDI.⁷

Two therapeutics are approved by the FDA for prevention of rCDI. The first one was approved in 2022 and is a rectal administration product derived from human donor stool (fecal microbiota live-jslm [Rebyota]).⁸ The other is an oral capsule (fecal microbiota spores live-bprk [Vowst]) containing live spores from fecal microbiota.⁶ With these exciting advances, we can now begin to address additional unmet needs with future research into microbiota restoration therapies.⁹