Patients with severe Clostridium difficile infection (CDI) who receive early fecal microbiota transplant (FMT) have improved survival, researchers from France report.
“We are proposing to use a relatively new weapon (FMT) for the first time in a new context: as a first line and as soon as possible,” Dr. Matthieu Million from Institut Hospitalo-Universitaire Mediterranee Infection, in Marseilles, told Reuters Health by email. “Immediate assessment of severity according to clear criteria is paramount, because in patients with non-severe infection there was no benefit on survival.”
Dr. Million’s team previously showed that early FMT is associated with improved survival in patients with CDI caused by the hypervirulent O27 ribotype. In their current report, they review outcomes of 111 patients (median age, 82; range, 34-104) hospitalized for CDI, including 66 patients treated with early FMT and 45 patients not treated with FMT.
The mortality rate at three months after diagnosis of CDI was 12.1 percent in the FMT group versus 42.2 percent in the antibiotic-only group, they reported online August 24 in Clinical Infectious Diseases.
In multivariable models, increasing age, increasing comorbidities, the O27 ribotype and severe CDI were independent predictors of higher mortality, whereas FMT treatment independently predicted better survival, with a number needed to treat (NNT) to save one life at three months of four. In subgroup analyses, FMT decreased mortality regardless of the O27 ribotype, and among patients treated with FMT, mortality did not differ between frozen and fresh FMT.
“In the present study, what was unexpected was that we were able to demonstrate that FMT avoided deaths even for non-O27 strains and that even very frail and very old people could benefit from it,” Dr. Million said.
After accounting for other variables, FMT decreased mortality only in patients with severe colitis.
“This has major consequences because we thought that the rapid and first-line FMT should be offered to everyone,” Dr. Million said. “Thanks to our study, in the absence of severity criteria, there is no urgency for FMT.”
He advised urgent graft in case of severe infection; for a non-severe infection, antibiotic treatment alone would be “reasonable,” though recurrent cases should be treated with a graft.
Dr. Million concluded, “In case of severe infection with C. difficile, do not wait; start vancomycin immediately and urgently transfer the patient to a center empowered to perform an urgent FMT.”
Dr. Lawrence J. Brandt from Albert Einstein College of Medicine, Montefiore Medical Center, in the Bronx, New York, told Reuters Health by email, “We and others have shown that FMT can be performed safely and effectively in patients with severe and complicated CDI to cure the index infection and prevent recurrent disease. We also have used it early in the course of disease, although that was not the specific focus of our and others’ publications.”
“The population studied (in the French study) was older than many other studies and again showed that FMT is effective in the elderly, who, of note, are more prone to CDI and to severe CDI and have a higher mortality than a younger population,” said Dr. Brandt, who was not involved in the new work.
“I do not think that FMT can be recommended as first-line therapy before long-term safety has been proven, which will take years and is the basis for the creation of the national FMT registry,” he said. “I believe that FMT is safe in the short-term, and when risk of death from CDI is high and there is no response to conventional antibiotics, I do not hesitate to resort to FMT. Earlier FMT is better than later FMT for patients very sick with CDI.”
Dr. Giovanni Cammarota from “A. Gemelli” University Hospital in Rome, who recently reported on the European consensus conference on FMT in clinical practice, told Reuters Health by email, “To date, FMT is recommended by international guidelines for the management of recurrent or refractory C. difficile infection. This study, in line with other reports, shows that FMT is effective against severe C. difficile infection, and should be introduced into the therapeutic algorithm of this condition in synergy with other therapeutic option (antibiotics, surgery).”
“As severe CDI is a life-threatening disease, dedicated protocols, including FMT, are therefore necessary to offer patients the best therapeutic option to cure this condition,” said Dr. Cammarota, who also was not involved in the study. “FMT is not an experimental treatment anymore; it could change the natural history of CDI in patients in clinical practice.”