Journal of Pediatric Gastroenterology & Nutrition:
Letters to the Editor
To the Editor: At present, it is unclear whether prebiotics are effective in the prevention of antibiotic-associated diarrhea (AAD) because only limited data are available. The only relevant, pediatric, double-blind randomized controlled trial involved 140 children (1–2 years of age) who were treated with amoxicillin for acute bronchitis. This study revealed no significant difference in the incidence of diarrhea in children receiving oligofructose and inulin administered in a milk formula (4.5 g/L) for 21 days after completion of antibiotic treatment compared with placebo (1). Because all of the prebiotics are not of equal efficacy, more studies are needed to determine which agents to use, as well as the timing, dosage, and mode of administration.
Here we report the results of a multicenter trial conducted by the Working Group for Probiotics and Prebiotics of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. The objective of this randomized double-blind controlled trial was to determine the efficacy of administering a combination of prebiotics, specifically inulin and fructo-oligosaccharides (FOS), for the prevention of diarrhea and AAD. Participants were eligible for the study if they were ages 6 months to 14 years and were prescribed short-term (<14 days) oral and/or intravenous antibiotic therapy for common infections (eg, upper or lower respiratory tract infection, otitis media, urinary tract infection, skin infection). Exclusion criteria included acute or chronic diarrhea, a chronic gastrointestinal disorder, antimicrobial therapy administered during the previous 30 days, use of any prebiotic and/or probiotic pharmaceutical products within 7 days before the study, a severe bacterial infection with systemic involvement, an immunodeficiency state, and a previous history of an antibiotic drug reaction. A total of 105 children (ages 6 months–11 years) with common infections were enrolled. They received antibiotic treatment plus inulin and FOS in age-dependent doses with a maximum dose of 5 g/day (n = 51) or a placebo (maltodextrin) (n = 54) orally for the duration of the antibiotic treatment. The study products were supplied at no cost by Sensus (Roosendaal, the Netherlands), which had no role in the design of the trial or in the collection, analysis, and interpretation of data. Each participating member obtained study approval from his or her local ethics committee. Parents were fully informed about the aims of the study, and informed consent was obtained from at least 1 parent. All of the analyses were conducted on an intention-to-treat basis. The study was stopped prematurely because of slow recruitment. Data from 92 children were included in the final analysis. There was no difference between the prebiotic and placebo groups in the proportions of participants with diarrhea, defined as ≥3 loose or watery stools per day for ≥48 hours occurring during or up to 2 weeks after the antibiotic therapy (3/45 [6.7%] vs 5/47 [10.6%], relative risk 0.63, 95% CI 0.16%–2.5%). There was also no difference between the prebiotic and placebo groups in the proportions of participants with AAD, diagnosed as above, when all of the stool bacterial cultures and the rotavirus assay were negative, with or without a positive stool assay for Clostridium difficile toxin (3/45 [6.7%] vs 4/47 [8.5%], relative risk 0.78, 95% CI 0.19%–3.3%). There was no need for discontinuation of the antibiotic treatment, hospital treatment because of diarrhea in the outpatients, or intravenous rehydration in any of the study groups. The mixture of prebiotics was well tolerated, and no adverse events associated with this therapy (or with the use of the placebo) were reported.
In conclusion, the administration of the 2 prebiotics (inulin and FOS) was not effective for preventing diarrhea and AAD. The overall frequency of diarrhea was low, and the study was underpowered. Thus, the results should be interpreted with caution. The present study does not allow any conclusions as to whether other prebiotic products are effective for the prevention of AAD. The efficacy and safety of each such product need to be evaluated separately.
1. Brunser O, Gotteland M, Cruchet S, et al. Effect of a milk formula with prebiotics on the intestinal microbiota of infants after an antibiotic treatment. Pediatr Res