The infusion of donor feces into the duodenum of patients with recurrent, often intractable Clostridium difficile infection led to a much higher rate of cure than did either vancomycin therapy or bowel lavage in a small, randomized, open-label clinical trial.
The trial was closed early to new enrollment after only 43 of its planned 120 patients had undergone randomization because an interim analysis by the trial’s data safety and monitoring board found that almost all patients in the two control groups had a recurrence, compared with ultimate resolution of diarrhea in 15 of 16 patients treated with fecal infusion.
There were no infectious complications from the fecal infusions, and the only adverse event was transient diarrhea immediately following the procedure, which resolved in all patients within 3 hours, according to Dr. Els van Nood of the University of Amsterdam Academic Medical Center and her associates. They reported their findings online Jan. 16 in the New England Journal of Medicine.
"We found that the infusion of donor feces is a potential therapeutic strategy against recurrent C. difficile infection. In our study, infusion of a relatively large amount of feces through a nasoduodenal tube had an acceptable adverse-event profile and was logistically manageable," they noted.
Currently there is no effective therapy for recurrent C. difficile infection of the gastrointestinal tract. Extended and repeated courses of vancomycin usually are prescribed, but the antibiotic’s efficacy is estimated to be only 60% for the first recurrence and declines substantially with each subsequent recurrence.
The reason for the waning of antibiotic effectiveness is not known for certain. Experts have proposed that C. difficile spores may persist in the gut and get reactivated over time; that antibody responses to Clostridium toxins diminish over time; or that persistent disturbance of the native intestinal microbiota causes reduced diversity, which in turn reduces natural resistance to C. difficile.
It was hoped that infusion of feces from healthy donors would address the last mechanism, restoring the normal microbiota and boosting host defenses against C. difficile. Several preliminary studies have produced promising results, but "experience with this procedure is limited by a lack of randomized trials supporting its efficacy and the unappealing nature of the treatment," Dr. van Nood and her colleagues said.
All the study subjects had persistent C. difficile infection, as evidenced by severe diarrhea with positive stool tests for the organism, after multiple courses of vancomycin and/or metronidazole.
Both patients and physicians are reluctant to choose donor-feces infusion until other measures have failed repeatedly. "It seems reasonable to initiate treatment with donor-feces infusion after the second or third relapse," the investigators wrote.
A total of 41 patients completed the study protocol. The trial compared the infusion of donor feces after pretreatment with a brief (4-day) course of vancomycin and bowel lavage (16 patients), a standard vancomycin regimen (12 patients), and a standard vancomycin regimen plus bowel lavage (13 patients). Bowel lavage was included because it has been used in previous studies of this new treatment and is thought to "reduce the pathogenic bowel content, facilitating colonization of healthy donor microbiota."
Most of the study subjects were elderly, with mean ages of 73 years, 66 years, and 69 years, respectively, in the three study arms.
Feces donors included 15 healthy volunteers aged 60 years and older who were screened for numerous potentially transmissible diseases. Fecal samples were collected just before the infusion was scheduled, and they were screened for parasites, C. difficile, and enteropathogenic bacteria. The samples were diluted with 500 mL of sterile saline, and the mixture was strained and poured into a sterile bottle.
A mean of 141 g of feces was infused through a nasoduodenal tube, and patients were monitored for 2 hours. Analysis of patients’ phylogenetic microarray profiles before and after treatment demonstrated "a major shift in the patients’ microbiota" from abnormal to normal diversity of organisms, Dr. van Nood and her associates said (N. Engl. J. Med. 2013 Jan. 16 [doi: 10.1056/NEJMoa1205037]).
The primary endpoint was cure without relapse within 10 weeks of treatment. Thirteen patients in the infusion group (81%) reached this endpoint after a single infusion. The remaining 3 patients had a second treatment, and 2 of them were cured, for an overall cure rate of 94% (15 of 16 patients).
In comparison, the cure rate with vancomycin alone was 31% (4 of 13 patients), and with vancomycin plus bowel lavage it was 23% (3 of 13).
At an interim follow-up of 5 weeks following initial treatment, C. difficile infection recurred in 1 patient (6%) in the infusion group, compared with 8 (62%) in the vancomycin-only group and 7 (54%) in the vancomycin-plus-lavage group.
