Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis

Jaime Altcheh, Mabel V Carosella, Ana Ceballos, Ulises D'Andrea, Sandra M Jofre, Carolina Marotta, Domingo Mugeri, Liliana Sabbaj, Adriana Soto, Constant Josse, Francois Montestruc, Lynne V McFarland, Jaime Altcheh, Mabel V Carosella, Ana Ceballos, Ulises D'Andrea, Sandra M Jofre, Carolina Marotta, Domingo Mugeri, Liliana Sabbaj, Adriana Soto, Constant Josse, Francois Montestruc, Lynne V McFarland

Abstract

Background: The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE.

Methods: A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes.

Results: Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P = .04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated.

Conclusion: In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea.

Trial registration: ClinicalTrials.gov NCT03539913.

Conflict of interest statement

JA, MVC, AC, SMJ, CM, DM, LS and AS received fees from Biocodex as study investigators. They have no other conflict of interest to declare. FM and CJ are paid consultants to Biocodex. LVM is on the Microbiome Advisory Board and a paid lecturer for Biocodex, France and received a consulting fee for writing the manuscript. The sponsor (Biocodex, France) was involved in the study design, the analysis and interpretation of data, the writing of the report and the decision to submit the paper for publication.

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1.
Figure 1.
CONSORT flow-chart of study participants. CONSORT = consolidated standards for reporting trials.
Figure 2.
Figure 2.
Adjusted mean duration of pediatric acute gastroenteritis (diarrhea by hours) by type of analysis and type of probiotic. *P = .04 compared to Bacillus clausii.
Figure 3.
Figure 3.
Kaplan–Meier plot of probability of diarrhea by hours for the 2 probiotic groups (Bacillus clausii O/C, SIN, N/R, T and Saccharomyces boulardii CNCM I-745).

References

    1. World Health Organization (WHO). Diarrhoeal disease. May 2, 2017. Available at: . [Access dtae September 9, 2020].
    1. UNICEF. “Diarrhoea October 2019. 2019. Available at: . [Access date October 27, 2020].
    1. Global Burden of Disease (GBD) 2016 Diarrhoeal Disease Collaborators. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18:1211–28.
    1. Mast TC, DeMuro-Mercon C, Kelly CM, et al. . The impact of rotavirus gastroenteritis on the family. BMC Pediatr. 2009;9:1–9.
    1. Guarino A, Aguilar J, Berkley J, et al. . Acute gastroenteritis in children of the world: what needs to be done? J Ped Gastroenterol Nutr. 2020;70:694–701.
    1. Szajewska H, Guarino A, Hojsak I, et al. . Use of probiotics for the management of acute gastroenteritis in children: an update. J Pediatr Gastroenterol Nutr. 2020;71:261–9.
    1. Hill C, Guarner F, Reid G, et al. . Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.
    1. McFarland LV, Evans CT, Goldstein EJC. Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis. Front Med. 2018;5:1–14.
    1. Davis EC, Dinsmoor AM, Wang M, et al. . Microbiome composition in pediatric populations from birth to adolescence: impact of diet and prebiotic and probiotic interventions. Dig Dis Sci. 2020;65:706–22.
    1. Dinleyici EC, Martinez-Martinez D, Kara A, et al. . Time series analysis of the microbiota of children suffering from acute infectious diarrhea and their recovery after treatment. Front Microbiol. 2018;9:1230.
    1. Monjaraz EMT, Arellano KRI, Mayer AL, et al. . Gut microbiota in Mexican children with acute diarrhea. An observational study. Ped Infect Dis J. 2021;40:704–9.
    1. Vanhee LM, Goemé F, Nelis HJ, et al. . Quality control of fifteen probiotic products containing Saccharomyces boulardii. J Appl Microbiol. 2010;109:1745–52.
    1. Sniffen JC, McFarland LV, Evans CT, et al. . Choosing an appropriate probiotic product for your patient: an evidence-based practical guide. PLoS One. 2018;13:e0209205e0209205.
    1. Szajewska H, Kolodziej M, Gieruxzczak-Bialek D, et al. . Systematic review with meta-analysis: Lactobacillus rhamnosus GG for treating acute gastroenteritis in children—a 2019 update. Alim Pharm Therap. 2019;49:1376–84.
    1. Szajewska H, Kołodziej M, Zalewski BM. Systematic review with meta-analysis: Saccharomyces boulardii for treating acute gastroenteritis in children—a 2020 update. Aliment Pharmacol Ther. 2020;51:678–88.
    1. Ianiro G, Rizzatti G, Plomer M, et al. . Bacillus clausii for the treatment of acute diarrhea in children: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2018;10:1074.
    1. McFarland LV, Srinivasan R, Setty RP, et al. . Specific probiotics for the treatment of pediatric acute gastroenteritis in India: a systematic review and meta-analysis. J Ped Gastro Nut Rep. 2021;2:e079.
    1. Majamaa H, Isolauri E, Saxelin M, et al. . Lactic acid bacteria in the treatment of acute rotavirus gastroenteritis. J Pediatr Gastroenterol Nutr. 1995;20:333–8.
    1. Asmat S, Shaukat F, Asmat R, et al. . Clinical efficacy comparison of Saccharomyces boulardii and lactic acid as probiotics in acute pediatric diarrhea. J Coll Physicians Surg Pak. 2018;28:214–7.
    1. Vineeth S, Saireddy S, Keerthi T, et al. . Efficacy of Bacillus clausii and Saccharomyces boulardii in treatment of acute rotaviral diarrhea in pediatric patients. Indonesian J Clin Pharm. 2017;6:91–8.
    1. Reddy BS, Paul S, Vohra P. Comparing the Role of Bacillus clausii and Saccharomyces boulardii in acute watery diarrhoea. Poster presentation at Pedgastrocon, September 29–30, 2013; Pune, India.
    1. Moher D, Hopewell S, Schulz KF, et al. . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomized trials. J Clin Epidemiol. 2010;63:e1–37.
    1. Guarino A, Ashkenazi S, Gendrel D, et al. . European Society for pediatric infectious diseases. European Society for pediatric gastroenterology, hepatology, and nutrition/European Society for pediatric infectious diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014. J Pediatr Gastroenterol Nutr. 2014;59:132–52.
    1. Ghanma A, Puttemans K, Deneyer M, et al. . Amsterdam infant stool scale is more useful for assessing children who have not been toilet trained than Bristol stool scale. Acta Paediatr. 2014;103:e91–2.
    1. Freedman SB, Eltorky M, Gorelick M. Evaluation of a gastroenteritis severity score for use in outpatient settings. Pediatrics. 2010;125:e1278–85.
    1. Schnadower D, Tarr PI, Gorelick MH, et al. . Validation of the modified Vesikari score in children with gastroenteritis in 5 U.S. emergency departments. J Pediatr Gastroenterol Nutr. 2013;57:514–9.
    1. Pais P, Almeida V, Yilmaz M, et al. . Saccharomyces boulardii: what makes it tick as successful probiotic? J Fungi (Basel). 2020;6:78.
    1. Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections. World J Gastroenterol. 2019;25:2188–203.
    1. Depoorter L, Vandenplas Y. Probiotics in pediatrics. a review and practical guide. Nutrients. 2021;13:2176.
    1. Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics. 2014;134:e176–91.
    1. Li Z, Zhu G, Li C, et al. . Which probiotic is the most effective for treating acute diarrhea in children? A bayesian network meta-analysis of randomized controlled trials. Nutrients. 2021;13:4319.
    1. Collinson S, Deans A, Padua-Zamora A, et al. . Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2020;12:CD003048.
    1. de Castro JA, Villa-Real Guno MJ, Perez MO. Bacillus clausii as adjunctive treatment for acute community-acquired diarrhea among Filipino children: a large-scale, multicenter, open-label study (CODDLE). Trop Dis Travel Med Vacc. 2019;5:14.
    1. Joshi S, Udani S, Sen S, et al. . Bacillus clausii septicemia in a pediatric patient after treatment with probiotics. Ped Infect Dis J. 2019;38:e228–30.
    1. Kothari D, Patel S, Kim SK. Probiotic supplements might not be universally-effective and safe: a review. Biomed Pharmacother. 2019;111:537–47.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться