The results of this randomized, double-blind, placebo-controlled trial have shown that the lactobacilli-fermented milk product BIO K+ CL1285® is effective in reducing the severity and incidence of AAD in patients treated with antibiotics in a hospital setting.
The duration of diarrhea used as a measure of severity of AAD, was 1.19 days in the placebo group and 0.67 days in the BIO K+ group. This is a statistically and clinically significant unadjusted reduction of 43.7% in the mean duration of diarrhea. After adjusting for baseline prognostic variables the results show that, on the average, diarrhea will be reduced by 51.5% in patients treated with BIO K+ compared to those treated with placebo. This reduction in the duration of diarrhea, which is both clinically important and statistically significant, has major implications for patient's quality of life as well as direct and indirect health care costs related to the management of AAD.
The results of this study showed a 33% unadjusted reduction in the risk of diarrhea (incidence) in the patients treated with BIO K+ compared to placebo. Although this treatment effect is clinically important, the study was not sufficiently powered to detect this effect size as statistically significant. The low power was due to higher (29.4%) than the expected 20% incidence of diarrhea in the placebo group. This is a possible weakness of the current study, which is related to the assumptions used for sample size calculations. The multivariate logistic regression analyses controlled for the effect of the covariates, thus reducing within group variance and improving the power of the study. These results showed that after adjusting for the effect of potential confounders, the treatment with BIO K+ resulted in a statistically significant 37.3% reduction in the risk of AAD. While the type of concomitant medication used may be associated with increased risk for diarrhea; the two groups were very well matched with respect to this parameter and therefore there is no concern for confounding on the treatment effect.
The results of the current study are comparable with others that have reported the effectiveness of probiotics in reducing the incidence of AAD [9
]. However, the majority of these studies have been conducted on smaller number of patients. Conversely, the current study was conducted in several centers across Canada and in a larger and more diverse patient sample that is representative of the target population. The pathogenesis of antibiotic related diarrhea is based on the disruption of the intestinal normal flora. Probiotics including lactobacilli are efficacious in restoring normal flora and thus preventing or reducing the duration of diarrhea. A similar mechanism of action for the benefits of probiotics has been noted for Crohn's disease[22
], irritable bowel syndrome [23
], ulcerative colitis [24
], and patients undergoing ileal pouch anal anastomosis [25
The major strength of the present study is inherited in the double blind, placebo controlled design. Given the merit of double blind, controlled trial, the results of the current study provide evidence that the BIO K+ CL1285® lactobacilli-fermented probiotic is effective in the prevention of antibiotic associated diarrhea. These results have important implications for the general target population treated with antibiotics in a hospital setting and show that treatment with BIO K+ CL1285® will reduce the duration of diarrhea by approximately one half and the risk for diarrhea by more than one third. This will result in significantly improved patient quality of life and health care cost savings by reduced hospitalizations and health care resource utilization.
In recent years there has been an increase in the incidence of C. difficile
infection in hospital settings, with the elderly hospitalized patients being at increased risk. In fact between 10-20% of C. difficile
cases are observed in the elderly patients [26
]. In the current study, despite the low overall incidence of C. difficile
, a lower rate was observed in the lactobacilli compared to the placebo group. It should be noted, however, that testing for C. difficile
was not conducted on all patients and that testing was dependent on the decision of the treating physician and hospital protocols. Further research on the assessment of the efficacy of BIO K+ in the prevention of CDAD is required as this nosocomial infection remains an important health issue worldwide.
Despite the high proportion of patients reporting at least one adverse event in each group, the majority (80%) of the events were mild in severity and the incidence was similar for the placebo and treatment groups. These results show that BIO K+ was overall safe and well tolerated.
In conclusion, this study demonstrates that probiotic prophylaxis with BIO K+ CL1285® is safe and efficacious in reducing the incidence and duration of antibiotic associated diarrhea in patients receiving antibiotic treatment in a hospital setting.