Treatment with Nontoxigenic C. difficile to Prevent CDI Recurrence

Recurrent Clostridium difficile infection (CDI) appears to stem from the germination of toxigenic C. difficile spores in the intestinal tract in the presence of an altered gut microbiome. The principal approaches being used today to prevent such recurrences are prolonged courses of antimicrobials active against C. difficile and restoration of a normal gut microbiome with fecal transplantation.

Some C. difficile strains lack the genes for toxin production, and these nontoxigenic (NTCD) strains can colonize the gut without causing disease. In an industry-supported, multinational, phase II, double-blind, dose-ranging trial involving adults with CDI, researchers examined whether the oral administration of one such strain, NTCD-M3, could lead to colonization with the strain and reduce the risk for CDI recurrence. Participants were randomized to receive 10⁴ spores per day for 7 days, 10⁷ spores per day for 7 days, 10⁷ spores per day for 14 days, or placebo.

A total of 168 patients — 139 with a single CDI episode and 29 with one recurrence —were enrolled and started treatment. Colonization with NTCD-M3 occurred in 69% of NTCD-M3 recipients overall (72% for 10⁷ spores/day for 7 days, 71% for 10⁷ spores/day for 14 days, 63% for 10⁴ spores/day). CDI recurred in 11% of all NTCD-M3–group participants versus 30% of placebo-group participants. Serious treatment-emergent adverse events emerged in 7% of placebo recipients compared with 3% of all NTCI-M3 recipients.