Probiotics May Prevent C. Difficile Diarrhea
By Charles Bankhead, Staff Writer, MedPage Today, Published: November 15, 2012
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston
Patients at risk of Clostridium difficile-associated diarrhea had a 66% lower infection rate when they received prophylactic probiotics, results of a meta-analysis showed.
Treatment with multispecies probiotics products was associated with a 75% reduction in the risk of C. difficile diarrhea, whereas single-species products reduced the risk by 50%. Serious adverse events were uncommon in patients who received probiotics.
The findings add to previous evidence that treatment with probiotics affords protection against diarrhea in at-risk populations, as reported online in Annals of Internal Medicine.
"Moderate-quality evidence supports a large protective effect of probiotics in preventing [C. difficile-associated diarrhea]," Bradley C. Johnston, PhD, of the Hospital for Sick Children Research Institute in Toronto, and co-authors wrote in conclusion.
"Given the low cost of probiotics and the moderate quality evidence suggesting the absence of important adverse events, there seems little reason not to encourage use of probiotics in patients receiving antibiotics who are at appreciable risk of [C. difficile-associated diarrhea]," they wrote.
Antibiotics have a recognized potential to disrupt gastrointestinal flora and predispose patients to opportunistic infections of the gastrointestinal tract. C. difficile is the pathogenic culprit that most often takes advantage of the breakdown in colonization resistance resulting from antibiotic treatment. The spectrum of C. difficile-related disease ranges from asymptomatic colonization to potentially fatal infection.
In developed countries, C. difficile is the leading cause of hospital-acquired infectious diarrheal disease. The typical patient is an older, hospitalized individual treated with broad-spectrum antibiotics. Since early in the previous decade, the frequency and severity of C. difficile-associated diarrhea have increased dramatically, including almost a twofold increase in the case fatality rate in the U.S., according to the background information.
Use of probiotics has grown in popularity as a means of maintaining intestinal health. The products are thought to maintain the integrity of gastrointestinal flora and to stimulate repopulation of endogenous microflora disturbed by antibiotics or other means.
Numerous studies have evaluated probiotics' therapeutic effects, but their safety and efficacy for prevention of C. difficile-associated diarrhea has not been studied extensively. Johnston and colleagues addressed the issue by performing a systematic review and meta-analysis of relevant literature.
They limited their search to randomized, controlled trials of antibiotic-treated adults and children who received any dose of any prespecified probiotic of any strain. Eligible studies had to include data on the incidence of C. difficile-positive diarrhea.
The search produced 20 studies suitable to include in the analysis. The trials involved a cumulative total of 3,818 patients. In 18 of 20 cases, the studies were placebo controlled. One study provided no treatment to the control group, and one study did not specify the type of comparator.
Probiotic products evaluated in the trials included one or more of the following: Bifidobacterium spp., Saccharomyces spp., Lactobacilli spp., and Streptococcus spp.
C. difficile-associated diarrhea was defined as any episode of diarrhea associated with a positive stool test for C. difficile.
Overall, prophylaxis with probiotics was associated with a relative risk of 0.34 for C. diff diarrhea compared with the control group (95% CI 0.24 to 0.49). The results further demonstrated that patients who received multispecies probiotics had a relative risk of 0.25 (95% CI 0.15 to 0.41), whereas those who received a single-species product had a relative risk of 0.50 (95% CI 0.29 to 0.84).
Subgroup analysis showed consistency of results in adults and children, with higher and lower doses of probiotics, with different probiotic species, and in studies with a higher or lower risk of bias.
The overall incidence of adverse events was 9.3% in patients treated with probiotics and 12.6% in the control group. Four trials reported no adverse events in either study arm. Three studies reported serious adverse events, and the most serious events occurred in patients in control groups.
Additionally, no serious adverse events were thought to be associated with probiotics treatment.
Acknowledging limitations of the study, the authors cited variation in C. difficile-associated diarrhea diagnostic methods among the trials included in the analysis, variability in patient risk in control groups, variation in exclusion criteria among the trials, and 13 trials with missing diarrhea data for 5% to 45% of patients.
Johnston disclosed a relationship with Bicodex.
Primary source: Annals of Internal Medicine
Johnston BC, et al "Probiotics for the prevention of Clostridium difficile associated diarrhea: A systematic review and meta-analysis" Ann Intern Med 2012; epub.