Medical Research: What is the background for this study? What are the main findings?
Dr. Gerding: Naturally occurring strains of C. difficile lack the genes for production of the toxins that cause C. difficile infection (CDI) and are known as non-toxigenic C. difficile (NTCD). These strains when ingested by patients whose normal microbiota is disrupted by antibiotic treatment will harmlessly colonize the colon and remain in the gut for weeks to months. Specific strains of NTCD found in patients were shown to colonize the gut and prevent C. difficile infection when challenged with toxigenic C. difficile strains in animal models. One such NTCD strain, NTCD-M3, was shown to be safe and well tolerated in human volunteer trials and was used in the present study to determine if it would prevent recurrence of C. difficile infection in patients who had just completed treatment with vancomycin or metronidazole of either their first CDI episode or first recurrence of
C. difficile infection. 168 patients were randomized to receive by mouth in a liquid form, either 10,000 spores/day of NTCD-M3 for 7 days, 10 million spores/day for 7 days, 10 million spores/day for 14 days, or an identical placebo for 14 days. Primary outcome was safety, and secondary outcomes were the percent who colonized the gut with NTCD-M3 in the time period from end of treatment to week 6, and the rate of recurrent CDI in the patients at week 6. The results showed that NTCD-M3 was safe and well tolerated, and colonized the gut of 69% of patients who received it. The C. difficile infection recurrence rate was 30% in the placebo patients and 11% in patients who received any of the NTCD-M3 doses (P<.006). The best dose tested was 10 million spores/day for 7 days which resulted in a recurrence rate of only 5% (p<.01 vs placebo). Colonization of the gut was not permanent, but lasted a maximum of 22 weeks. The summary conclusion is that NTCD-M3 is safe, colonized the gut, and when it colonized the gut, reduced recurrence of C. difficile infection to 2% (p<.001 vs patients who were not colonized).
Medical Research: What should clinicians and patients take away from your report?
Dr. Gerding: This is a promising safe and simple method to prevent recurrence of
C. difficile infection in patients treated with standard antibiotics, metronidazole or vancomycin (or both). It needs confirmation in a larger phase 3 trial using the best tested dose and duration.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Gerding: This is a phase 2 trial, so a phase 3 confirmatory trial in patients still needs to be done, but the method is a safe and simple addition to standard treatment and with use of the optimal dose in phase 3 should reduce C. difficile infection recurrence to approximately 5%. Other studies of NTCD-M3 in patients are needed to show that it can be used to prevent first episode of CDI by giving NTCD-M3 to patients taking antibiotics who are at high risk for CDI. This could provide a transient (not permanent) protection against CDI during high-risk periods of antibiotic use.
Dale N. Gerding, MD et al. Administration of Spores of Nontoxigenic Clostridium difficile Strain M3 for Prevention of Recurrent C difficile InfectionA Randomized Clinical Trial. JAMA, May 2015 DOI: 10.1001/jama.2015.3725
MedicalResearch.com Interview with: Dale N. Gerding, MD (2015). Non-Toxic Spores May Prevent C. difficile infection MedicalResearch.com : https://medicalresearch.com/infections/c-difficile/non-toxic-spor…cile-infection/13844