Probiotic Selection for Acute Pediatric Diarrhea

A head-to-head comparison

By Zach Kadro, ND

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Reference

Asmat S, Shaukat F, Asmat R, Bakhat HFSG, Asmat TM. Clinical efficacy comparison of Saccharomyces boulardii and lactic acid as probiotics in acute pediatric diarrhea. J Coll Physicians Surg Pak. 2018;28(3):214-217.

Objective

To compare the effectiveness of oral rehydration and antibiotic treatment plus the addition of either Saccharomyces boulardii or lactic acid–producing probiotics for treating acute pediatric diarrhea.

Design

Randomized trial

Participants

Children (N=200) ages 6 months to 5 years admitted to the hospital for acute diarrhea (3 or more loose, watery stools per day) of less than 14 days in duration were enrolled in the study. Children already treated with probiotics or antibiotics, or suffering from immunodeficiency, malnutrition, or severe dehydration were excluded from participation in the study.

Participants were randomized into 2 groups: Group A (n=100; 61 were age 6 months-3 years and 39 were age 4-5; 48 boys and 52 girls) received Saccharomyces boulardii, while Group B (n=100; 62 were age 6 months-3 years and 38 were age 4-5; 57 boys and 43 girls) received lactic acid–producing probiotics.

Intervention

Group A received an oral dose of Saccharomyces boulardii, 150 mg (for ages 6 months-1 year) or 250 mg (for ages 2-5 years), divided into 2 doses, and delivered in 20 mL of water, twice daily for 5 days.

Group B received an oral dose of lactic acid–producing probiotics, 150 mg (for ages 6 months-1 year) or 250 mg (for ages 2-5 years), divided into 2 doses, and delivered in 20 mL of water, twice daily for 5 days.

All participants were treated with intravenous ceftriaxone antibiotics and oral rehydration.

Study Parameters Assessed

Baseline complete blood count, urinalysis, and physical examination were performed. Data on the frequency and consistency of stools per day was collected throughout the study.

Primary Outcome Measures

Resolution of acute diarrhea (fewer than 3 loose, watery stools per day).

Key Findings

There was a statistically significant difference in treatment effect between Groups A and B. In Group A, 45 participants were treated effectively with Saccharomyces boulardii; in Group B, 26 participants were treated effectively with lactic acid–producing probiotics (P=0.004). In other words, 45% of participants who were taking Saccharomyces boulardii (Group A) had resolution of acute diarrhea, compared to only 26% of those taking lactic acid–producing probiotics (Group B).

Stratification by duration of treatment demonstrated that within 1 to 7 days of beginning treatment, 21 participants in Group A and 15 participants in Group B had resolution of acute diarrhea (P=0.34), which was not statistically significant. However, within 7 to 13 days of beginning treatment, 24 participants in Group A and 11 participants in Group B had resolution of acute diarrhea, which was statistically significant (P=0.001).

Practice Implications

Diarrheal illness in children is a global public health crisis. The second leading cause of death in children worldwide, diarrhea claims the lives of 1.5 to 2 million children under the age of 5 each year. Children in resource-limited areas around the globe have an average of 3 episodes of diarrheal illness per year; infants experience an average of 6 episodes per year.1

A growing body of evidence suggests that probiotics can be helpful as adjunct therapy in acute pediatric diarrhea. The findings of the present study support conclusions of a comprehensive systematic review and meta-analysis published by Feizizadeh et al in 2014. The review, which analyzed 22 clinical trials, concluded that Saccharomyces boulardii used as adjunct therapy reduces the duration of acute pediatric diarrhea.2 A 2015 systematic review and meta-analysis by Ahmadi et al, which analyzed 14 articles, concluded that duration of acute rotavirus diarrhea in children was reduced with administration of Lactobacillus rhamnosus GG and other probiotics compared with control.3

Going forward, clinical practice can be further guided by research focusing on which strains, and at what doses, will be most clinically effective.

Many of the studies to date have been placebo-controlled trials rather than head-to-head comparisons of different probiotics. We can now presume probiotics are more effective than placebo for resolving pediatric diarrhea. Going forward, clinical practice can be further guided by research focusing on which strains, and at what doses, will be most clinically effective.

In the present study by Asmat et al, Saccharomyces boulardii was effective in more patients than lactic acid–producing probiotics for the treatment of acute pediatric diarrhea, with 45% having resolution of diarrhea compared to 26%, respectively. The present study corroborates the findings of a 2010 study by Eren et al, which compared Saccharomyces boulardii to yogurt containing Lactobacillus bulgaricus and S thermophiles as adjunct treatment of acute pediatric diarrhea. By day 3 of the study, 48.5% of participants treated with Saccharomyces boulardii had resolution of diarrhea compared to 25.5% of those treated with Lactobacillus bulgaricus and S thermophiles.4 Both studies support the idea that Saccharomyces boulardii should be considered the first choice probiotic for adjunct treatment of acute diarrhea.

In the present study, the finding that response to treatment between the 2 groups was comparable for the first 7 days (21% vs 15%) was intriguing. It was not significantly different until days 7 to 13, when an additional 24% of participants in Group A had resolution of diarrhea vs only 11% in Group B. This implies that treatment with probiotics, and specifically Saccharomyces boulardii, should be considered for at least 2 weeks from the onset of acute diarrheal symptoms to achieve the potential therapeutic benefit.

Although not examined in this study, it would be interesting to see if participants in either group who did not respond after 2 weeks of treatment with oral rehydration, antibiotics, and probiotics (which would include 55% of the Saccharomyces boulardii-treated Group A and 74% of Group B) would have responded to longer treatment, higher doses, or a more diverse blend of probiotic strains.

Given the public health implications of diarrheal illness, especially in resource-limited countries, and the millions of children dying annually, the positive results from studies of probiotic therapy should prompt further investigation to demonstrate the effectiveness of Saccharomyces boulardii and Lactobacillus rhamnosus GG and other promising strains. Moreover, combining strains with known benefit for acute diarrhea may increase effectiveness and provide a more foolproof way of obtaining the highest response rate to treatment.

The present study had a few areas of concern which warrant caution in the interpretation of the results. The methodology did not specify the exact probiotic products used in the study, who supplied them, how they were stored, if they were tested for viability, or the number of colony forming units contained in each dose. In addition, the only description we have for the product used for Group B participants is “lactic acid–producing probiotics,” rather than any particular strain(s) of bacteria.

Another area of concern was Table II, where results for age-based stratification were presented. The numbers for efficacy in Group B in Table II did not correctly add up to the efficacy data presented in Table I, and therefore could not be interpreted as accurate; consequently, these numbers were not included in the Key Findings section of this review. The error was likely a simple mistake, but because it was not discovered in any stage of development, peer review, or publication, it raises concerns about the overall quality of the study.

Interesting as well was the choice to treat all participants with antibiotic therapy, which comes with its own risks (eg, antibiotic-associated diarrhea) and is not considered a first-line treatment for diarrheal illness, which is usually viral in origin. There may be specific indications for the antibiotic use, not listed in the paper, related to the geographic area where the study was conducted (Pakistan).1

Lastly, the trial design, which compared 2 adjunct probiotic interventions, might have been improved by the addition of a placebo control arm and a probiotic combination arm.

Despite its flaws, the paper still deserves consideration, given the ever-growing body of evidence that supports a broad range of therapeutic applications for probiotics. Probiotics, at best, may provide symptom benefit with very low risk of side effects, which is always something worthy of pursuit.

About the Author

Zach Kadro, ND, is a naturopathic doctor and second-year resident at the Goshen Center for Cancer Care, where he is completing the nation’s only 2-year hospital-based residency program in naturopathic oncology. Kadro earned his Bachelor of General Studies degree from the University of Michigan (Ann Arbor, MI) prior to completing his Doctor of Naturopathic Medicine degree at Bastyr University (Kenmore, WA). In addition to seeing patients at the cancer center, Kadro is also involved in developing a clinical trial to examine the effect of standard of care plus naturopathic care vs standard of care alone on the incidence and severity of chemotherapy-induced peripheral neuropathy.

References

  1. Harris JB, Pietroni M. Approach to the child with acute diarrhea in resource-limited countries. UpToDate. https://www.uptodate.com/contents/approach-to-the-child-with-acute-diarrhea-in-resource-limited-countries. Updated September 24, 2018. Accessed January 4, 2019.
  2. Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics. 2014;134(1):176-191.
  3. Ahmadi E, Alizadeh-Navaei R, Rezai MS. Efficacy of probiotic use in acute rotavirus diarrhea in children: a systematic review and meta-analysis. Caspian J Intern Med. 2015;6(4):187-195.
  4. Eren M, Dinleyici EC, Vandenplas Y. Clinical efficacy of Saccharomyces boulardii and yogurt fluid in acute non-bloody diarrhea in children: a randomized, controlled, open label study. Am J Trop Med Hyg. 2010;82(3):488-491.