Is primary prevention of Clostridium difficile infection possible with specific probiotics?

Background: The efficacy of probiotics for the prevention of Clostridium difficile infection (CDI) is highly controversial, particularly with regard to the prevention of recurrent CDI. We hypothesize that primary prevention of CDI among patients receiving antibiotics might be a more achievable goal for probiotics than prevention in patients with previous CDI where the host flora is markedly altered. Methods: We conducted a literature search for randomized, placebo-controlled efficacy studies of probiotic use among adults receiving antibiotics, in which CDI was one of the outcomes measured. In addition, we conducted meta-analyses of probiotics that were included in more than one randomized trial. Results: Eleven studies were identified; most were seriously underpowered to determine the efficacy of probiotics in the prevention of CDI. Two showed significantly lower rates of CDI among the probiotic recipients. A meta-analysis of three studies that used the probiotic combination Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R and a combined analysis of those studies with four studies that used Saccharomyces boulardii, showed lower CDI rates in recipients of probiotics compared with recipients of placebo (risk ratio = 0.39; 95% confidence interval 0.19-0.79). Conclusions: While potential flaws in study design were identified, a review of the available literature suggests that the primary prevention of CDI with specific probiotic agents may be achievable. Additional studies of sufficient size and with rigorous design are needed to confirm these findings.