Recurrent C difficile Infection Prevention: Efficacy and Administration of Fecal Microbiota Therapy

Over the past couple of years, new therapeutics have been developed to prevent the recurrence of Clostridioides difficile (C difficile) infection (CDI). C difficile is a bacterium that can take hold and multiply in the gut (lower intestines). The intestinal tract contains millions of microorganisms, both good and bad, that collectively comprise the gut microbiome. Disruptions in the gut microbiome composition can result in dysbiosis, which can enable infections such as C difficile to occur.

Certain situations, such as taking antibiotics to treat infection, may change the balance of microorganisms in the gut, allowing C difficile to multiply and cause dysbiosis. Other factors that increase the risk of C difficile includes being older than age 65, hospitalization, a weakened immune system, and a previous history of CDI.

CDI causes debilitating symptoms such as severe diarrhea, fever, stomach tenderness or pain, loss of appetite, nausea, and colitis. This often can be the start of a vicious cycle of recurrence, causing a significant burden for patients and the health care system. It has been estimated that up to 35% of CDI cases recur after initial diagnosis and people who have had a recurrence are at a significantly higher risk of further infections.

CDI causes debilitating symptoms such as severe diarrhea, fever, stomach tenderness or pain, loss of appetite, nausea, and colitis. Image Credit: © Artur - stock.adobe.com

On November 30, 2022, the FDA approved fecal microbiota, live - jslm (RBL), which is the first and only single-dose microbiome-based treatment for the prevention of recurrent CDI in adults after taking antibiotics for recurrent CDI. This live biotherapeutic product is a pre-packaged, single-dose 150 mL microbiota suspension for rectal administration consisting of a liquid mix of up to trillions of live microbes, including Bacteroides. Each dose is delivered directly to the gut microbiome and administered by a health care provider (HCP) within minutes in one visit.

Sharon Rimon, NP, Reddy GI Associates, Mesa, Arizona, has been actively administering RBL since it became available in February 2023. In the Q&A below, Rimon shares her experience with rectal suspension deliveryadministration for RBL and why this mode of administration can be effective and beneficial.

Question: What is rectal suspension delivery, and can you provide an example of where it is used in delivering treatment to patients?

Sharon Rimon, NP: Rectal suspensions are liquid preparations for rectal use and are typically used to treat or manage localized diseases of the colon. These suspensions are not new and have been used in cases when quick therapeutic response is required. Rectally administering RBL ensures that treatment is delivered directly to the gut microbiome where it is needed. A single, 150 mL dose contains up to trillions of live microbes and can be easily and quickly administered in a clinical setting.

Question: Why would rectal administration of RBL work well for the prevention of recurrence of CDI?What are some specific benefits of administering RBL rectally?

Rimon: With rectal administration of RBL, treatment is delivered directly to the gut microbiome. Further, rectal administration is conducted in a clinical setting by an HCP, taking the burden off the patient and putting it in the hands of the HCP. It requires no bowel prep in advance of being administered, and no anesthesia. This is a quick procedure, administered in minutes. Most noteworthy is that it is a ‘one and done’ treatment to prevent the recurrence of CDI.

Question: Is there any training, preparation or special requirements needed for the rectal administration of this microbiota suspension by HCPs? And in your clinical experience, is the use of RBL easily adopted as a practical office-based treatment?

Rimon: A study presented at IDWeek 2023 found that having a protocol and procedures in place for management, drug ordering, patient communications, and administration resulted in better success. I would agree with these results—in our experience, we have found RBL administration to be easy to adopt in our practice. The more real-world experience you have in delivering RBL to patients, the better you become at executing the whole process. It’s also important to let patients know in advance what to expect.

Question: About how long does the whole procedure take and is there any prep needed?

Rimon: The entire process isn’t burdensome to the patient. It begins with the patient finishing their antibiotic treatment 1 to 3 days in advance of RBL administration. There is no bowel prep, laxatives, fasting, anesthesia, or colonoscopy required.

On the day of the patient’s appointment, the patient goes to the doctor’s office, where we explain the procedure and what to expect. We then have the patient lie on the exam table, either on their side or in a knees-chest position. Patients might feel slight pressure upon rectal administration of RBL and a cold sensation. The administration takes about 6 minutes, followed by 15 minutes for observation and to minimize cramping. Patients can leave the doctor’s office once the observation time is completed. 

Question: What can HCPs share with patients, so they are better aware of the simple administration of RBL?

Rimon: There are many advantages to the rectal suspension delivery of RBL. First, there is no prep needed prior to administration. Second, it is a quick procedure that only takes minutes both for administration and observation. Since anesthesia is not required, patients can even drive themselves home as soon as the procedure is done. Finally, this is a ‘one and done’ treatment—one dose in one visit.

The clinical trial data supporting the FDA approval showed RBL to be superior to placebo in reducing recurrent CDI after standard-of-care antibiotic treatment. More than 90% of study participants who achieved treatment success remained free of CDI recurrence through 6 months.Adverse events (AEs) were primarily mild-to-moderate in intensity and there were no treatment-related serious AEs. Patients who have a history of severe allergic reactions (eg, anaphylaxis) to RBL or any of its components are not candidates for treatment.

Question: What do pharmacists need to know most about this novel fecal microbiome treatment for the prevention of recurrence of CDI and its administration for their practice?

Rimon: Pharmacists and pharmacy professionals play a critical role in patient education and are invaluable resources to help patients understand the importance of a healthy microbiome and how dysbiosis and infections may occur, and why. Pharmacy professionals often receive questions from their customers about different diseases and conditions, so it is helpful for them to stay informed of treatment, particularly new treatments and their administration, dosing, and AEs.

Although retail pharmacists don’t dispense or administer RBL, they should be aware of its availability and ordering process, particularly for those working in hospitals or health care centers. RBL can be ordered through a network of specialty distributors and specialty pharmacies. RBL is shipped frozen to HCP offices to thaw ahead of administration, and ordering is recommended 2 to 4 days prior to the administration appointment.