Giving people harmless spores of Clostridium difficile by mouth proved safe and effective in stopping recurrent bouts of C. difficile infection (CDI) in a phase 2 study.

C. difficile is an important cause of health care-associated infections, killing an estimated 29,000 in the United States each year. Rates of CDI remain at “unprecedented” high levels in U.S. hospitals, the researchers note in JAMA May 5.

CDI is often triggered by exposure to antibiotics, particularly in the elderly, and has a recurrence rate of 25 to 30 percent among affected patients.

Gastrointestinal colonization by nontoxigenic C. difficile stains has been shown in earlier human and animal studies to have the potential to prevent CDI.

Building on this earlier work, Dale Gerding, MD, of Loyola University Chicago in Maywood, Illinois, and colleagues tested the safety and efficacy of spores of the nontoxigenic M3 strain for prevention of CDI recurrence. All trial participants had successfully completed antibiotic treatment for a first episode or first recurrence of CDI.

The patients received 10,000 or 10 million spores per day in liquid form for seven or 14 days, or matching placebo; of the 168 who started treatment, 157 completed it.

Dr. Gerding noted in a JAMA podcast that the nontoxigenic C. diff strain was “safe and colonization occurred in about 70 percent of patient given these spores.”

Among those who took any dose of M3, 11 percent experienced a repeat infection within 42 days compared with 30 percent of those who took placebo, “which was highly statistically significant,” he said.

The best dose regimen was 10 million spores given for seven days, which had a recurrence rate of 5 percent, “also highly statistically significant compared to placebo,” Dr. Gerding said.

The recurrence rate was lowest for those who became colonized with the M3, at “only 2 percent,” he added. Patients who did not become colonized but received nontoxigenic strain M3 had recurrence rates that were comparable to placebo. “Colonization with this strain following its administration correlates with protection against recurrence,” Dr. Gerding said.

He added, “The data suggest that as the patient’s normal bacterial complement is recovering, eventually they will lose colonization with this nontoxigenic strain and we think that is a good point because it means they are not going to have a significant alteration of their microbiota permanently but rather temporary protective colonization.”

A phase 3 trial now in the planning stages will assess the ability of M3 to reduce recurrence of C. diff in a larger population using the best dose identified in this study, Dr. Gerding said.

A primary prevention study would also be worthwhile, he added—that is, giving nontoxigenic strain M3 to patients who are taking antibiotics “to see if we can colonize them and as a result protect them against C. difficile infection in the first place.”

“I think we are going to come up with new novel strains of bacteriotherapy or biotherapeutics that will really help us prevent some of the unintended consequences of antibiotic therapy,” Dr. Gerding said.

The study was sponsored by ViroPharma Incorporated, which is now part of the Shire group of companies. Dr. Gerding reports holding patents for the prevention of CDI licensed to ViroPharma/Shire and providing consultancy for ViroPharma/Shire.