A new Cochrane Review has found that stool transplantation is significantly more effective at resolving recurrent Clostridioides difficile infection (rCDI) than antibiotics.
In their analysis of six randomized clinical trials (RCTs) involving 320 patients, the reviewers found the use of fecal microbiota transplantation (FMT), which involves transplanting bacteria from the stool of a healthy donor into a patient with a disrupted gut microbiome, likely leads to a large increase in resolution of rCDI symptoms in immunocompetent patients compared with antibiotic treatment. The review also found that FMT may result in fewer adverse events and a reduction in all-cause mortality.
Breaking the cycle of recurrent C diff
C difficile is a bacterium that causes severe diarrhea and inflammation of the colon. It causes more than 450,000 healthcare- and community-associated infections, and as many as 30,000 deaths, in the United States each year. In addition, people with CDI are at increased risk of getting infected again, often multiple times.
Although FMT is still considered an investigational treatment by the US Food and Drug Administration, several observational studies have shown that the procedure might cure more than 90% of patients with rCDI, and it is now recommended by the Infectious Diseases Society of America and American College of Gastroenterology as a treatment option following a second or further recurrence. At least 10,000 FMT procedures for rCDI are performed each year, using screened stool from healthy donors.
After a person with a C. diff infection gets treated with antibiotics, there is about a 25 percent chance that they will have another episode of C. diff infection in the next 8 weeks.
One of the reasons that FMT is increasingly seen as a preferred option for rCDI is because antibiotics—which are a major risk factor for initial CDI episodes—can wipe out both the good and bad bacteria in the gut microbiome, creating an imbalance that enables C difficile to flourish and attack the colon. As a result, repeated antibiotic treatments for rCDI can lead to more recurrences.
In a Cochrane press release, senior reviewer Aamer Imdad, MBBS, an associate professor at SUNY Upstate Medical Center who specializes in pediatric gastroenterology, explains that repeated antibiotic treatments for rCDI creates a cycle that's difficult to break out of.
"After a person with a C. diff infection gets treated with antibiotics, there is about a 25 percent chance that they will have another episode of C. diff infection in the next 8 weeks," Imdad said. "The risk of recurrence increases to about 40 percent with the second episode and to nearly 60 percent with the third episode."
The aim of FMT, Imdad adds, is to introduce healthy donor bacteria to reverse the dysbiosis (imbalance in the gut's microbial composition) caused by antibiotics and reduce the risk of recurrence.
Significant increase in rCDI resolution
To determine how effective FMT is for rCDI, Imdad and his collegues analyzed data from six RCTs conducted in five countries—two in Denmark, and one each in Canada, Denmark, Italy, and the United States. Five of the studies excluded people who were immunocompromised, while one included only a handful of immunocompromised patients.
All RCTs were conducted on adults, with a mean age ranging from 52 to 73 years, and all involved participants with at least one recurrence of CDI after a course of antibiotics (one study enrolled only patients with two or more recurrences, and another only patients with three or more).
All six studies had an arm that received FMT from a healthy donor for the treatment of rCDI, delivered via different methods (colonoscopy, nasoduodenal tube, and enema). The comparator arms in five of the studies received the standard-of-care antibiotic vancomycin, with one having an additional group that received fidaxomicin. Of the 320 patients, 133 were in the FMT group and 187 in the control group. All six studies assessed the safety and efficacy of FMT.
The primary outcomes were the proportion of patients with resolution of rCDI and serious adverse events. Secondary outcomes included all-cause mortality.
Pooled results from the six RCTs showed that the use of FMT likely leads to a 92% increase in resolution of rCDI compared with the comparator group (risk ratio [RR], 1.92; 95% confidence interval [CI], 1.36 to 2.71). The overall certainty of the evidence supporting that conclusion was deemed moderate.
The reviewers also found a slight reduction in adverse events (RR, 0.73; 95% CI, 0.38 to 1.41) and all-cause mortality (RR, 0.57; 95% CI, 0.22 to 1.45) among patients who received FMT. But in both cases, the number of events that occurred was so small that the evidence was not considered conclusive.
The reviewers say that, because of the low number of immunocompromised patients in the RCTs, conclusions cannot be drawn about the risks or benefits of FMT for rCDI in the immunocompromised population. In addition, they note that the review does not provide evidence regarding the long-term safety of FMT.