Probiotics are safe and effective for preventing Clostridium difficile–associated diarrhea (CDAD) in children and adults taking antibiotics, according to a systematic review published online May 31 in the Cochrane Database of Systematic Reviews. "In the short-term, taking probiotics in conjunction with antibiotics appears to be a safe and effective way of preventing diarrhoea associated with Clostridium difficile infection," senior author Bradley C. Johnston, PhD, from the Hospital for Sick Children Research Institute in Toronto, Ontario, Canada, said in a news release. "The introduction of some probiotic regimens as adjuncts to antibiotics could have an immediate impact on patient outcomes, especially in outbreak settings. However, we still need to establish the probiotic strains and doses that provide the best results, and determine the safety of probiotics in immunocompromised patients." The reviewers searched PubMed (1966 - 2013), EMBASE (1966 - 2013), Cochrane Central Register of Controlled Trials, CINAHL (1982 - 2013), AMED (1985 - 2013), ISI Web of Science, and other sources, and they also contacted industry representatives. Inclusion criteria were randomized controlled trials evaluating any strain or dose of probiotics for prevention of CDAD or C difficile infection. Of 1871 studies identified, 31 met inclusion criteria; these studies enrolled a total of 4492 participants. In 23 trials, enrolling a total of 4213 participants, that evaluated CDAD prevention, probiotic use was associated with a significant 64% reduction in risk (2.0% incidence of CDAD in the probiotic group vs 5.5% in the control group; relative risk [RR], 0.36; 95% confidence interval [CI], 0.26 - 0.51). On the basis of the overall evidence, the reviewers had moderate confidence in this large relative risk reduction. Probiotics were not associated with significant reduction in the secondary outcome of incidence of C difficile infection (13 trials; 961 participants; 12.6% incidence of CDAD in the probiotic group vs 12.7% in the control group; RR, 0.89; 95% CI, 0.64 - 1.24). "We think it's possible that probiotics act to prevent the symptoms of C. difficile infection rather than to prevent the infection itself," Dr. Johnston said. "This possibility needs to be investigated further in future trials, which should help us to understand more about how probiotics work." In 26 studies (3964 participants) investigating adverse events, probiotic use was associated with a 20% reduction in risk for adverse events (RR, 0.80; 95% CI, 0.68 - 0.95). Abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance were among the most common adverse events in both treatment and control groups. "Based on this systematic review and meta-analysis of 23 randomized controlled trials including 4213 patients, moderate quality evidence suggests that probiotics are both safe and effective for preventingClostridium difficile-associated diarrhea," the review authors write. Limitations include the inability to rule out significant clinical heterogeneity, pooling of trials using different species or strains of probiotics to prevent CDAD, and significant missing data from multiple trials. "Although probiotics are clearly superior to placebo or no treatment for preventing CDAD, further head-to-head trials are warranted to distinguish optimal strains and dosages," the review authors conclude. "To allow for an accurate assessment of the potential for adverse events, especially among immunocompromised individuals, standardized and clear adverse event reporting is essential for future trials.