Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. The Cochrane Gut group have produced more than 220 reviews, including some that investigate treatments for Clostridioides difficile infection. These were added to in April 2023, with a new review of the use of fecal microbiota transplantation for the treatment of recurrent infection. Here’s Zev Minkoff from Valley Children's Hospital in Madera in the USA to tell us more about the condition and this treatment.

Zev: Clostridioides difficile, previously known as Clostridium difficile, often referred as ‘C. difficile’ or ‘C. diff’ is a gram positive spore forming bacteria. C. diff can cause life-threatening diarrheal illness in individuals with an unhealthy mixture of gut bacteria, known as dysbiosis. There are many reasons a person can have dysbiosis, including proton pump inhibitor therapy, inflammatory bowel disease, and immunocompromised states, but the most common cause of dysbiosis is treatment with antibiotics. While antibiotics can be very effective against bacterial infections, including C. difficile, they can also harm the beneficial bacteria that are vital to a healthy intestinal microbiome. First line treatment for C. difficile infection often involves treatment with antibiotics which target C. difficile, but sometimes the infection recurs when the antibiotics are stopped, a situation known as recurrent C difficile infection. The use of antibiotics to treat recurrent C. difficile infection therefore has the potential to be a double-edged sword as antibiotics can exacerbate dysbiosis.
Fecal microbiota transplantation, or ‘FMT’ is the administration of stool from a healthy donor to the GI tract of a recipient, with the goal that the recipient’s dysbiosis is changed to a healthier balance of gut bacteria, which can prevent the recurrence of C diff infection. The objective of our study was to assess the efficacy and safety of FMT for the treatment of recurrent C. difficile infection.
We found six randomized controlled trials, including 320 adult study participants. Two of the studies were conducted in Denmark, and one each in the Netherlands, Italy, Canada, and the United States. The route of administration was the upper gastrointestinal tract via a nasoduodenal tube in one study, two studies used enema only, two used colonoscopic only delivery, and one used either nasojejunal or colonoscopic delivery. Five studies had at least one comparison group that received vancomycin.
The risk of bias assessments did not find an overall high risk of bias for any outcome. A moderate certainty showed that use of FMT likely leads to a large increase in resolution of recurrent C diff, as 77 percent of people who received a stool transplant did not experience reinfection within eight weeks of treatment, compared to 40 percent of those who received other treatments. Exclusion of one study that had included a small proportion of immunocompromised patients, did not change the results. The risk of serious adverse events and all-cause mortality may be lower in the FMT group however the confidence interval around the summary estimate was wide and a possible small increase in the risk of these outcomes could not be ruled out. The data for rates of colectomy and quality of life scores were not available.
In summary, the use of FMT likely leads to a large increase in the resolution of recurrent C diff infection in adult immunocompetent patients compared to other treatments such as antibiotics. The risk of serious adverse events may be lower in the short term with FMT. Additional data from large national registry databases may prove helpful in assessing the potential long-term risks of using FMT for the treatment of recurrent C difficile.

Mike: If you would like to find out more about fecal microbiota transplantation as a treatment for C. difficile, the Cochrane review is available online. If you go to Cochrane library dot com and search for ‘fecal microbiota transplantation’ you’ll see a link to this review and the others of FMT.