Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?
Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.
Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.
Setting: Forty-four centers in the U.S., Canada, and Europe.
Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.
Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.
CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.
Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.
Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.