February 2023

Clostridioides difficile infection (CDI) continues to be a strong public health threat. The burden on the healthcare system has been significant, with inpatient costs associated with acute CDI nearing $5 billion in the US. Patients and caregivers experience enormous levels of suffering with potentially debilitating and life-threatening diseases such as CDI. Awareness efforts and environmental guidelines put forth by entities such as the CDC and the Infectious Diseases Society of America are helping shape and improve the approach to infection control. An area of particularly urgent need is expanding treatment options for patients with recurrent CDI. A new approval for a first-in-class microbiota-based live biotherapeutic is a step toward addressing this clinical challenge.

Dysbiosis, or the imbalance of the microbiome of the gut, may lead to illness in patients, which can be severe. Antibiotics are common culprits of causing this imbalance since both good and bad bacteria are affected during treatment. If a patient carries or is exposed to C. difficile spores, the opportunistic bacteria could take hold and cause an infection. This risk is greater with courses of antibiotics, hospitalizations, or older individuals. Some indicators of CDI are diarrhea, nausea, pain, and potentially colitis. In cases of more severe infection, additional complications and disease can result, including dehydration, kidney failure, toxic megacolon, sepsis, and even death. Treatment for CDI can be complicated and lengthy and may only provide a temporary resolution. Up to 30% of individuals who experience CDI develop a recurrent case. As incidences of CDI repeat in a patient, the likelihood of future recurrences increases, putting further stress on their already greatly taxed health.

The standard approach to treatment of severe CDI includes vancomycin, which is bactericidal and effective for gram-positive bacteria. It alters the bacterial cell wall and results in cell death. For recurrent CDI, antibody-based therapy is introduced, using Zinplava (bezlotoxumab), which interferes with the protein toxin production of C. difficile. Fidaxomicin is also used in recurrent CDI, another bactericide for C. difficile. Unfortunately, even with repeated targeted treatments, CDI may not be eradicated, and a patient may continue to have recurrences. In order to disrupt the excruciating cycle in patients, clinical measures may need to be taken to correct the dysbiosis through the introduction of a biotherapeutic. However, until recently, there has not been a standardized therapeutic option for gut microbiome restoration. The new FDA approval for Rebyota (fecal microbiota, live-jslm) opens the pathway for providing regulated access to treatment that offers a sustained improvement in prevention of recurrent CDI.

Rebyota is indicated for the prevention of recurrence of CDI in individuals aged 18 years and older, following antibiotic treatment for recurrent CDI. The treatment consists of a single 150mL rectal dose of a microbiota suspension. The fecal microbiota in Rebyota includes Bacteroides, which are beneficial bacteria that assist in the needed diversity in the gut microbiome. Only qualified human donors supply the pathogen-tested fecal matter used to manufacture Rebyota. Screening for potential donors includes blood and stool testing to identify and prevent inclusion of any detrimental bacteria, parasites, or viruses. In clinical trial, 90% of patients with treatment success at the eight-week primary endpoint still experienced a continued outcome of no recurrent CDI for six months. These are encouraging results and showcase the benefit of using microbiota-based therapy.

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