Probiotics for the Prevention of Antibiotic-Associated Diarrhea

Evidence-Based Answer Probiotics reduce the risk of developing antibiotic-associated diarrhea (Strength of Recommendation (SOR) A). (See appendix for the Strength of Recommendation taxomony.) Saccharomyces boulardii and Lactobacillus species have been shown to reduce the risk of antibiotic-associated diarrhea (SOR A). Probiotics should be recommended for the prevention of antibiotic-associated diarrhea (SOR C). However, the duration and dosage for effective treatment have not been established.

the prevention of AAD has been studied widely and overall has positive results in reducing AAD.
Probiotics reduce the risk of developing AAD.Hempel et al. 2 performed the most exhaustive meta-analysis on randomized control trials (RCTs) of probiotics for the prevention of AAD.Their subgroup analysis of 14 RCTs limited to participants aged 18 to 65 years demonstrated that probiotic administration was associated with reduction of AAD by 46% (RR = 0.54, 95% CI: 0.34 -0.85, NNT = 13). 3A pooled analysis of all 45 study arms meeting our inclusion criteria gave similar results (RR = 0.59; 95% CI: 0.53 -0.67, NNT = 15).The results suggested that probiotics are efficacious in the prevention of AAD.Though the majority of studies focused on Lactobacillus, many strains and combinations of probiotics were used and reporting often was insufficient to determine the exact regimen used in a particular study.Importantly, regardless of subgroup analysis, the results remained statistically significant.This meta-analysis was unable to identify which strains or doses were truly beneficial.
A recent Cochrane meta-analysis focused on AAD studies that included a measure of C. difficile. 1The subset of 19 studies in adults with AAD showed a 37% reduction in risk (RR = 0.63; 95% CI: 0.51 -0.76).A risk reduction of 64% was reported in the 19 studies in adults with C. difficile-associated diarrhea (RR = 0.36, 95% CI: 0.24 -0.52).
S. boulardii and Lactobacillus reduce the risk of developing AAD.3][4][5] Overall, the results consistently have shown a significant reduction in AAD with the use of each of these probiotics.
McFarland's meta-analysis included 10 RCTs comparing S. boulardii to placebo and found a significant protective effect against AAD with number needed to treat being 10.2 (pooled RR = 0.47, 95% CI: 0.35 -0.63, p < 0.0001, NNT = 10.2). 5 Two meta-analyses included 12 RCTs (8 overlapping) using Lactobacillus species only.Pooled analysis of each showed that there was a 34% reduction in risk of AAD. 2,3Overall, the trials showed a benefit to the use of S. boulardii or Lactobacillus in the reduction of AAD.
Probiotics should be used for the prevention of AAD.2][3][4][5] Hempel showed that the number needed to treat to prevent one case of AAD was only 13. 2 Furthermore, studies consistently note that adverse effects of probiotics rarely were reported. 6Based on the available data, probiotics should be used for the prevention of AAD.However, research is inconclusive regarding the best probiotic regimen.More research is needed to determine clear recommendations including which strain or combination of strains to use, dosage, and duration of treatment.Many of the meta-analyses identified heterogeneity among probiotic regimens as a concern.

Recommendations from Others
An expert panel convened for the third time at Yale University in 2011 to evaluate the use of probiotics. 8Their consensus was that there is grade A evidence (strong, positive studies in the literature) for prevention of AAD with L. rhamnosus GG and S. Boulardii, and the evidence for the mixture of L. casei DN-114 001, L. delbrueckii subspecies bulgaricus, and S. thermophilus is also strong.However, the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA) in their 2010 guidelines on Clostridium difficile infections have recommended that probiotics not be used for primary prevention of C. difficile.They also noted that reported cases of fungemia have occurred with the use of S. boulardii in severely ill and immunocompromised patients and advised against its use in these patients. 9