Anaerobically cultivated human intestinal microbiota as first-line treatment for Clostridium difficile infection

C lostridium difficile infection (CDI), most often resulting from an antibiotic-induced disturbance of the healthy intestinal microbiota, is an increasing health problem (1 3). Antibiotics such as metronidazole or vancomycin are well-established and effective treatment options for first occurrences of CDI (4, 5) (socalled primary), but up to one third of patients experience treatment failure or recurrent disease within a few weeks (6 8). Repeated courses of antibiotics may be effective, but multiple recurrences are common (9). Recurrent CDI may result from re-infection with the same or a different C. difficile strain. Up to 50% of recurrences may be reinfections with strains different from the primary infection reinforcing the notion that appropriate colonization is disturbed after antibiotic treatment (10). Fecal microbiota transplant (FMT) has been shown to be effective and safe in recurrent CDI in multiple uncontrolled studies (11), and recently, a randomized controlled trial (RCT) showed FMT to be superior to high-dose vancomycin for recurrent CDI (12). Theoretically, FMT as first-line treatment can prevent the vicious cycle of both types of re-infections (same or different strain) by rapidly restoring a favorable colonic microbial environment, and thus leaving the patient less susceptible to either kind of CDI recurrence. Reduced need for resistance-driving antibiotics and reduced proliferation of other resistant pathogens are possible advantageous spinoff effects of FMT as the primary treatment of CDI. This is a description of the design of an ongoing RCT to compare the effect of intestinal microbiota transplantation with the effect of standard metronidazole treatment in primary CDI. Based on the high recurrence rate of CDI after treatment with antibiotics and the convincing results of FMT for recurrent CDI, we hypothesize that intestinal microbiota transplantation can be beneficial also in the treatment of primary CDI (13). The aim of this study is to investigate whether an anaerobically cultivated human intestinal microbiota (ACHIM) is more effective than metronidazole in inducing a durable cure for primary CDI (ClinicalTrials.gov identifier NCT02301000).