Intestinal Microbiota Therapy Versus Metronidazole for Primary Clostridium Difficile Infection: a Randomized Controlled Trial

Up to one third of patients with clostridium difficile infection treated with antibiotics experience recurrent or relapsing symptoms within a few weeks. Even with subsequent antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota transplantation (FMT) has been shown to be significantly more effective in curing recurrent CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen transmittance and the cumbersome and costly process of finding a donor and screen for communicable disease. The effect of FMT for recurrent CDI, however, suggests that this therapy may be more effective than antibiotics in inducing a durable cure also for primary CDI.

We aim to use an anaerobically cultivated human intestinal microbiota (ACHIM) that has been extensively tested for pathogens, from a donor screened for communicable diseases, to avoid the need for a case-by-case donor screening. The term Intestinal Microbiota Therapy (IMT) will be used to describe the ACHIM treatment.

Patients with a first occurrence of CDI defined by diarrhea, as defined by the World Health Organization, and a positive stool test for toxigenic Clostridium difficile will be randomized 1:1 to either a 10-day course of metronidazole 400 mg t.i.d. or a rectal instillation of 60 ml ACHIM suspension.

Patients will be contacted on day 4 by an unblinded study investigator and on days 35 and 70 by a blinded study investigator to evaluate the treatment effect. In addition, the patients will register the frequency of bowel movements on days 1-4, 7, 14 and 21.

In the case of clinical deterioration, appropriate measures will be undertaken according to current guidelines.