USE OF THE PROBIOTIC Lactobacillus reuteri DSM 17938 IN THE PREVENTION OF ANTIBIOTIC-ASSOCIATED INFECTIONS IN HOSPITALIZED BULGARIAN CHILDREN: A RANDOMIZED, CONTROLLED TRIAL.

Objective: To evaluate the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of antibiotic-associated diarrhoea and Clostridium difficile-related infections in hospitalized children in a Bulgarian hospital. Study design: Children (n=100, aged 3 to 12 years) admitted to the hospital for acute infections were enrolled in a randomized, double-blind, placebo-controlled trial. They were assigned to receive either a probiotic supplement containing 1 x 10(8) CFU Lactobacillus reuteri DSM 17938 in the form of one chewable tablet once per day (n=49) (BioGaia AB, Stockholm, Sweden) or placebo (n=48). The probiotic or placebo was taken 2 hours after lunch each day, during the entire period of antibiotic treatment at the hospital and for additional 7 days. Results: Data from 97 children were included in the final analysis. The incidence of diarrhoea (defined as at least 3 loose or watery stools per day in a 48-hour period that occurred during or up to 21 days after cessation of antibiotic treatment) was unexpectedly low in both groups - L. reuteri (n=1) versus placebo (n=1): 2,04 vs. 2,1 per 100 (p>0,05, risk ratio 1,02, 95% CI 0,7-1,4). L reuteri DSM 17938 did not significantly affect the incidence or severity of AAD diarrhoea and Clostridium difficile infection. We found unusually high colonisation rate of non-symptomatic C. difficile measured by toxin-specific ELISA. There was no difference between the probiotic and placebo groups for any of the other secondary outcomes (i.e., incidence of mild diarrhoea, frequency of stool samples positive for C. difficile toxin A and B at the beginning and at the end of study period, frequencies of other gastrointestinal symptoms in the same study period) (p<0,05). No adverse events were reported. Conclusion: Due to the low incidence of antibiotic-associated diarrhoea in both groups, no conclusion can be made on the efficacy of L. reuteri DSM 17938 on AAD in hospitalized Bulgarian children. The probiotic did not affect the non-symptomatic high rate of C. difficile colonisation (33.3% in the placebo and 38.8% in the L. reuteri group at baseline) in this population. There was also no difference between groups regarding different gastrointestinal side effects.