Non‐antimicrobial “Outside the Box” CDI Management. Part 2

More recently, whey protein in immunized cow’s milk, which contains high levels of secretory IgA, has been used clinically for CDI recurrence prevention and CDI primary treatment. Results remain inconclusive, because the CDI recurrence prevention trial (2 weeks of daily anti- C. difficile whey protein after standard CDI therapy) resulted in a recurrence rate of 10% (11 of 109 episodes of CDI) but was open label and uncontrolled. A primary treatment trial, which was randomized and double blinded, compared C. difficile immune whey at 200 mL 3 times a day with metronidazole at 400 mg 3 times a day for 14 days. There was initial treatment response in 20 (100%) of 20 patients treated with metronidazole and 16 (89%) of 18 patients treated with C. difficile immune whey. The rate of sustained response at 70 days was 55% with metronidazole treatment (9 recurrences) and 56% with C. difficile immune whey treatment (6 recurrences). The study was interrupted because of bankruptcy of the sponsor, but C. difficile immune whey was as effective as metronidazole in this small study.

Biotherapeutic agents. Although not likely to be as effective as primary therapy, biotherapeutic agents (live microorganisms) may be beneficial in restoring microbiomic protection against CDI following disruption by antimicrobial therapy. Although so-called probiotic approaches to prevention and treatment of CDI have been largely inconclusive or disappointing to date (and are not covered in this review), fecal transplants have been highly effective at preventing additional CDI episodes in patients with multiple recurrences of CDI. The success of fecal transplants in preventing additional recurrence of CDI supports the concept that there are microorganisms in feces that can reestablish protection against subsequent CDI. Identification of the specific protective organism(s) has not been successful, but a synthetic mixture of bacteria was successful in reestablishing protection against additional CDI recurrence in humans in one uncontrolled report. A prospective, randomized trial of fecal transplants for recurrent CDI is underway in the Netherlands.

It has been known for >25 years that nontoxigenic C. difficile strains occur naturally and, when given to hamsters during or after antibiotic treatment, are able to harmlessly colonize the gut and prevent subsequent infection challenge with toxigenic strains of C. difficile. It has also been shown in patients that natural asymptomatic colonization with C. difficile (toxigenic or nontoxigenic strains) is associated with decreased risk of CDI. The use of nontoxigenic C. difficile to prevent primary or recurrent CDI is an attractive strategy because it can be administered orally as spores that pass through the gastric acid barrier readily, and if as effective in humans as in hamsters, will provide protection within 1–2 days. Specific strains of nontoxigenic C. difficile may be more efficient and durable as colonizing organisms; however, the mechanism by which nontoxigenic C. difficile is able to prevent colonization by toxigenic strains has not been elucidated. Human safety trials of nontoxigenic C. difficile were completed in early 2010, and trials involving patients are expected to begin in late 2010.