The present study demonstrated that a fermented milk, combining L acidophilus and L casei at a daily dose of 50×109 colony forming units administered to hospitalized patients receiving antibiotics is effective in the prevention of AAD.
We found that the lactobacilli preparation was effective in reducing the incidence of AAD when compared with a placebo, even though only 89 patients were recruited in the predesignated study period. This study protocol was conducted as part of a pharmacy residency program and was therefore limited to nine months. In spite of a relatively small group, we were able to reach a statistical conclusion by witnessing a higher baseline risk of AAD (35.6% in the placebo group) than initially expected. A previous meta-analysis (20
) has shown an overall benefit of administering probiotics as a preventive method for AAD. However, of the nine studies retained for the analysis, only three studies showed some statistically significant advantage; two involved a Saccharomyces
species, and one involved a Lactobacillus
species. The latter was one of the studies with the biggest weight in the global analysis. Those studies were heterogenous in the duration of treatment, dosage and antibiotics being used. Because our study was placebo-controlled and randomized, it strengthened the role of lactobacilli-based probiotics as prophylactic agents in the prevention of AAD.
Furthermore, the proportion of AAD due to C difficile
infection was very high compared with that observed in previous studies (43.6% [seven of 16 cases] in the placebo group versus 10% to 20%) (1
). This observation concurs with the 2003 to 2004 fourfold increase in the number of CDAD cases that affected the Montreal area (26
). The prevention of CDAD is an important outcome to consider, because this condition has been associated with an increased mortality and morbidity (2
). Although there was a trend in the reduction of the incidence of CDAD in the lactobacilli group compared with the placebo group, this difference was not statistically significant. However, the present study was not specifically designed to assess this as a primary outcome and too few patients were randomized to adequately detect such an effect of the lactobacilli preparation.
The lactobacilli-fermented milk did not have any impact on the hospital length of stay. It is worth mentioning that 12 of 23 AAD cases (52.1%) occurred after discharge from the hospital. The long-term follow-up of patients after their antibiotic courses enabled us to witness that the majority of all the episodes occurred for both groups after the end of antibiotic therapy.
It would have been useful to determine the efficacy of the lactobacilli preparation with regard to specific antibiotics classes, because the incidence of AAD may have varied according to which antibiotic was prescribed. However, it was not feasible because of the variety of antibiotic combinations used concurrently, and the relatively small number of patients with diarrhea. In the present study, the use of beta-lactams was more frequent in the placebo group. However, this disparity was not found to affect the AAD occurrence according to a logistic regression analysis adjusting for potential confounders.
Almost one-half of the patients in both groups reported at least one adverse event. Because the placebo was a lactoserum and the study preparation a fermented milk, they would be expected to cause GI disturbances. In fact, most of the adverse events were related to the GI tract. No severe or life-threatening adverse event related to the use of the lactobacilli preparation was reported, although there were some withdrawals associated with the occurrence of an adverse event. Because some studies (14
) have reported the development of septicemia and endocarditis with the use of lactobacilli, the present study voluntarily excluded immunocompromised patients, patients at risk for aspiration and GI translocation, and patients with damaged or artificial heart valves. Therefore, the fermented milk was well tolerated, and should not cause any problem if given to patients with no potential risk factors.