Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE)

Background Diarrhea is among the main causes of pediatric mortality in the Philippines. Probiotics have been shown to be beneficial in the management of acute diarrhea. Accordingly, the aim of this population-based study was to assess the safety and effectiveness of Bacillus clausii as an adjunct to standard therapy in Filipino children with acute community-acquired diarrhea of viral origin or associated with antibiotic administration. MethodsA total of 3178 patients (median age of 2years) were enrolled in this open-label, multicenter, observational study, and were treated with one to two vials of Bacillus clausii in the following bacterial stains: O/C, SIN, N/R, and T (oral suspension of 2 billion spores per 5-mL vial) for 5 to 7days. Diarrhea duration, number of stools per day, improvement in gastrointestinal symptoms, children's overall acceptability of Bacillus clausii therapy, and safety and tolerability were assessed. Concomitant treatment with oral rehydration solutions (26.6%), zinc (23.9%), and antibiotics prescribed for conditions other than diarrhea (13.6%) was recorded during the study. All other probiotics and antidiarrheals were prohibited. Results Therapy with Bacillus clausii was well-tolerated, and the adverse event rate was very low (0.09%). All reported adverse events, which included vomiting, erythematous rashes and stool color change, were mild to moderate. In more than half of the per-protocol population (1535/2916; 52.6%), diarrhea was resolved within the first 3days of treatment with Bacillus clausii. There was no significant difference (p=0.297) in mean diarrhea duration between patients with either antibiotic-associated (3.31.3days) or viral diarrhea (3.4 +/- 1.3days). However, children who only received Bacillus clausii supplementation without zinc had a significantly shorter diarrhea duration (3.3 +/- 1.3days) compared to zinc-treated children (3.6 +/- 1.6days; p<0.001). Bacillus clausii significantly reduced the mean number of stools per day, from 5.2 +/- 2.0 stools at baseline to 1.2 +/- 0.6 stools at study end (p<0.001). Similarly, the proportion of patients with loose stools decreased from 81.6% at baseline to 9.2% at end of treatment period. Acceptability of Bacillus clausii therapy was high. Conclusion This study adds knowledge on the good safety profile and on the effectiveness of Bacillus clausii as an adjunct treatment for acute childhood diarrhea.