Fecal transplantation in recurrent C. difficile infection [Classics Series]

Classics Series, Landmark Trials in Medicine

1. Treating recurrent C. difficile infection with infusion of donor feces resulted in significantly higher cure rates than treating with vancomycin-alone or vancomycin with bowel lavage.

2. Adverse events immediately after feces infusion included diarrhea, cramping, and belching.

Original Date of Publication: January 31, 2013

Study Rundown: Previous studies have demonstrated that vancomycin is superior to metronidazole in treating severe Clostridium difficile-associated diarrhea, and that fidaxomicin is non-inferior to vancomycin in achieving clinical cure of C. difficile infection, but significantly reduces the rate of recurrence. In many patients, however, antibiotic treatment does not lead to sustained response, and these patients often require repeated or long tapering courses of vancomycin in attempts to achieve cure. While many factors have been blamed for C. difficile recurrence, one commonly cited reason is the destruction of the normal intestinal flora from repeated bouts of antibiotic therapy. Earlier non-randomized trials had explored the efficacy of gastrointestinal infusions of feces from healthy donors to treat recurrent C. difficile infection, and the results were promising. The purpose of this small randomized, controlled trial was to explore the efficacy of donor feces infusion in treating recurrent C. difficile infection.

In summary, patients receiving donor feces infusion were significantly more likely to achieve cure without relapse in the 10 weeks after starting therapy. While these results are promising, larger, multicentre trials are needed to study the generalizability of these findings. Moreover, trials with longer follow-up are necessary to assess the duration of the effect.

Click to read the study in NEJM

In-Depth [randomized controlled trial]: This open-label, randomized, controlled trial was originally published in NEJM in 2013. Participants in the trial were randomized to three treatment groups: 1) infusion of donor feces (preceded by a short course of vancomycin and bowel lavage), 2) a standard vancomycin regimen, and 3) a standard vancomycin regimen with bowel lavage. Patients were eligible for the trial if they were >18 years old, had a life expectancy >3 months, and had a relapse of C. difficile after an adequate course of antibiotics (≥10 days of vancomycin or metronidazole). Exclusion criteria included recent chemotherapy, HIV infection with CD4<240, prolonged use of prednisolone ≥60 mg daily, pregnancy, use of antibiotics for other infections, and admission to intensive care or requiring vasopressors. Patients who experienced recurrence after the first infusion were given a second infusion from a different donor. The primary endpoint was cure without relapse in the 10 weeks after starting therapy, or 10 weeks after the second infusion.

A total of 43 patients underwent randomization. In the feces infusion group, 81% of patients were cured after the first infusion, and 94% were cured overall. Cure rates were 31% and 23% for the vancomycin-alone and vancomycin with lavage groups, respectively. Patients in the feces infusion group had significantly higher rates of cure (P<0.01 for both comparisons after one infusion, P<0.001 for overall cure rate). Most patients (94%) had diarrhea immediately after receiving donor feces, while cramping (31%) and belching (19%) were also common. These symptoms resolved within 3 hours in all patients.

Image: PD

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