Fecal bacteriotherapy may be effective in treating relapsing C. difficile infection

A 2-year-old girl received a successful fecal transplant that resolved an ongoing battle with a Clostridium difficile infection that several antibiotic regimens failed to cure, according to a recently published case study.

Researchers from Massachusetts General Hospital and Harvard Medical School noted that the patient presented to her primary care provider with a 1-week history of abdominal discomfort and loose stools containing blood and mucus. After C. difficile toxin was identified in her stool, she was administered a 10-day course of metronidazole (125 g orally three times daily) that resolved abdominal pains but not the diarrhea.

The abdominal cramps recrudesced, at which point physicians administered a 30-day course of vancomycin at 125 mg orally 4 times daily and long-term probiotic therapy with Lactobacillus rhamnosus GG.

Two days after the discontinuation of vancomycin, symptoms and bloody diarrhea returned, along with laboratory results that confirmed that C. difficile toxin. Vancomycin treatment was reinitiated and augmented with rifamixin 100 mg orally 3 times daily.

A probiotic regimen of Saccharomyces boulardii and L. rhamnosus GG accompanied the antibiotics. This regimen was effective until 14 days after rifamixin was discontinued, when bloody diarrhea recurred despite ongoing vancomycin treatment.

As vancomycin therapy continued, metronidazole 100 mg 4 times daily for an additional 14 days replaced the rifamixin treatment. Symptoms and abnormal stools resolved during treatment with metronidazole and over an 8-week period in which vancomycin therapy was tapered.

Another relapse occurred 4 days after vancomycin was discontinued. Analysis of C. difficile toxin taken from the patient’s stool at this time indicated that in comparison with minimum inhibitory concentrations (MICs) for more than 200 toxin-producing strains, the vancomycin and metronidazole MICs for this strain were at or below the MIC₉₀, according to the results.

At this stage, staggered antibiotic treatment was initiated. The schedule was as follows: vancomycin for 2 weeks; nitazoxanide 100 mg orally twice daily for 3 days; vancomycin for 2 weeks; rifamixin 125 mg orally twice daily for 7 days; and then a course of pulsed-dose vancomycin every third day tapered over a 6-week period. This regimen was administered concomitantly with the aforementioned probiotics.

The patient’s condition normalized during this treatment, but loose stools with mucus and abdominal pain returned when antibiotic therapy ceased.

The clinicians conducted a fecal transplant using the patient’s father — who had a negative screening test result — as a donor. Bacteriotherapy protocol was modified to suit the young patient.

Abdominal symptoms and diarrhea resolved within 36 hours of transplantation. Follow-up tests at 2 weeks, 3 months and 6 months yielded negative C. difficile toxin results and no symptoms or abnormal stools.

A possible explanation for the efficacy of fecal transplantation is that the “donors’ robust and diverse gut microbiota or other soluble compounds in the stool suppress C. difficile by competition for intestinal barrier function or tissue repair,” the researchers wrote.

Other possible ways fecal bacteria may modulate the immunity of the recipient include secreting antimicrobial substances, upregulating anti-inflammatory factors, suppressing pro-inflammatory factors, triggering protective innate immune responses or stimulating phagocytes, natural killer cells and regulatory T cells, according to the researchers.

“We have demonstrated that fecal bacteriotherapy may well prove to be a practical and effective therapy for relapsing [C. difficile infection] in young children,” they wrote. However, “until the effectiveness and safety of the proposed protocol can be evaluated further, this strategy should be reserved for children in whom appropriate antibiotics have failed in the setting of severe or prolonged symptomatic disease.”

Russell G. Pediatrics. 2010;doi:10.1542/peds.2009.3363.