Oral Liquid Formulation of C. Diff Reduced CDI Recurrence

A non-aggressive Clostridium difficile strain significantly reduced the risk of Clostridium difficile infection (CDI) recurrence.

A non-aggressive Clostridium difficile strain significantly reduced the risk of Clostridium difficile infection (CDI) recurrence in a small study published in the Journal of the American Medical Association.

Nontoxigenic C. difficile strains, which lack the genes required for toxin production, have shown promise as a treatment to prevent CDI. 

Researchers randomly assigned 173 adult patients with a confirmed diagnosis of CDI (first episode or first recurrence) who had successfully completed treatment with metronidazole, oral vancomycin, or both prior to enrollment to receive one of four treatments:

  • Oral liquid formulation of nontoxigenic C difficile strain M3 (VP20621; NTCD-M3), 104 spores/day for 7 days
  • 107 spores/day for 7 days
  • 107spores/day for 14 days
  • Placebo for 14 days

Among the 157 patients who completed the study, CDI recurrence was 11% among all patients receiving NTCD-M3 and 30% among patients receiving placebo. The lowest recurrence rate was in patients receiving 107 spores/d for seven days (5%). Fecal colonization occurred in 71% of patients with 107 spores/day and 63% with 104 spores/day). Colonization with NTCD was associated with reduced recurrence of CDI, as 2% of patients who were colonized experienced CDI recurrence compared to 31% of patients who received NTCD-M3 but were not colonized.

One or more treatment-emergent adverse events were reported in 78% of NTCD-M3 patients and 86% of patients in the placebo arm.

Diarrhea and abdominal pain were reported in 46% and 17% of NTCD-M3 patients and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 3% of NTCD-M3 patients and 7% of placebo patients; 10% of NTCD-M3 patients and 2% of placebo patients reported headache.

This mechanism of action is unknown, but it is believed that NTCD-M3 occupies the same metabolic or adherence niche in the gastrointestinal tract as toxigenic C. difficile. Once established, it could dominate resident or newly ingested toxigenic strains, according to the study authors. Based on the small sample size in this research, the results will need to be confirmed in larger studies.


  1. Gerding D, JAMA. Doi:10.1001/jama.2015.3725.

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This article originally appeared on MPR