Clostridioides difficile (formerly named Clostridium difficile, and widely known as C. diff) is a Gram-positive, spore-forming, obligate anaerobe that causes life-threatening diarrhea in people who take antibiotics, are hospitalized or in nursing homes, and people with weakened immune systems.(1)

C. difficile secretes toxins TcdA and TcdB, which are responsible for causing massive damage to the gut epithelium by inducing a strong inflammatory response.

Symptoms associated with C. difficile infections (CDI) range from diarrhea to pseudomembranous colitis, toxic megacolon, sepsis with organ failure and even death. It is estimated that C. difficile causes approximately half a million infections in the United States each year.

Additionally, approximately one in six people who have had C. difficile will become re-infected in the subsequent 2-8 weeks.(2,3)

Recently, the FDA issued a warning with respect to the utilization of PPIs and risk of developing Clostridium difficile infections (CDI).

The most commonly known medications to cause CDI are antibiotics. However, available studies suggest an association and increase in risk for CDI with PPI use as well.

Findings from a systematic review and meta-analysis by Trifan et al. suggest a significant association between the use of proton pump inhibitors (PPI) and the risk of development of CDIs.(4)

PPIs are medicines that treat gastric acid-related diseases such as gastroesophageal reflux, peptic ulcer, Helicobacter pylori infection, dyspepsia, and stress ulcers.(3)

PPIs are sold by such brand names as Prilosec, Nexium, Prevacid, and Protonix. PPIs inhibit the hydrogen-potassium ATPase pump in gastric parietal cells, which decrease acid secretion and cause a deficiency of stomach acid.

Trifan’s meta-analysis included an initial analysis of 956 studies which involved 356,683 patients. The evidence in these studies suggest that acid suppressive therapies, such as PPIs, facilitate vegetative C. difficile survival and growth, increasing the likelihood of acquiring CDI.

Furthermore, since approximately one in six people who suffer a CDI will experience the infection again, alternative therapies are needed to help mitigate or cure recurrent CDIs. As of November 2022, FDA approved the first fecal microbiota product for the prevention of CDI recurrence in adults who have completed antibiotic treatment for recurrent CDI.(5)

Fecal microbiota therapy (FMT) facilitates restoration of the normal gut microbiome flora to prevent further CDI incidents. FMT is a procedure where healthy bacteria is taken from the feces of a carefully screened donor to be introduced to the colon of the recipient.(6)

The normal flora will outcompete the C. difficile and prevent the re-infection event. The studies for the new therapy, called Rebyota, involved 978 patients who had a history of one or more occurrences of CDI.

The absence of CDI diarrhea within 8 weeks of administration of Rebyota was considered a successful treatment. A statistical analysis from the studies estimated a success rate of 70.6% at preventing recurrent CDI in the Rebyota group, which was significantly higher than the placebo group (success rate of 57.5%).(5)

As more research takes place to study CDIs and more treatment options emerge, individuals who suffer this unfortunate infection will have the opportunity to get their life back on track.

By Anna Klavins and Elide Herrera