Probiotic selection for acute pediatric diarrhea

Relation

Asmat S, Shaukat F, Asmat R, Bakhat HFSG, Asmat TM. Clinical effectiveness comparison ofSaccharomyces boulardiiand lactic acid as probiotics for acute pediatric diarrhea.J Coll Doctors Surg Pak. 2018;28(3):214-217.

Objective

To compare the effectiveness of oral rehydration and antibiotic treatment plus the addition of bothSaccharomyces boulardiior lactic acid producing probiotics for the treatment of acute pediatric diarrhea.

Draft

Randomized trial

Participant

The study included children (N=200) aged 6 months to 5 years who were hospitalized for acute diarrhea (3 or more loose, watery stools per day) lasting less than 14 days. Children who had already been treated with probiotics or antibiotics or who suffered from immunodeficiency, malnutrition or severe dehydration were excluded from participation in the study.

Participants were randomized into 2 groups: Group A (n = 100; 61 aged 6 months to 3 years and 39 aged 4 to 5 years; 48 boys and 52 girls) received Saccaromyces boulardiiwhile group B (n = 100; 62 aged 6 months to 3 years and 38 aged 4 to 5 years; 57 boys and 43 girls) received lactic acid-producing probiotics.

intervention

Group A received an oral dose ofSaccharomyces boulardii150 mg (for ages 6 months to 1 year) or 250 mg (for ages 2 to 5 years), divided into 2 doses and administered 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 to 1 year) or 250 mg (for ages 2 to 5 years), divided into 2 doses and administered in 20 ml of water twice daily for 5 days.

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

Study parameters assessed

Initially, a complete blood count, urinalysis, and physical examination were performed. Data on the frequency and consistency of bowel movements per day were collected throughout the study.

Primary outcome measures

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

Key insights

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

Stratification by treatment duration showed that within 1 to 7 days of starting 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 starting treatment, resolution of acute diarrhea occurred in 24 participants in Group A and 11 participants in Group B, which was statistically significant (P=0.001).

Practice implications

Diarrhea in children is a global public health crisis. Diarrhea is the second leading cause of death in children worldwide, claiming the lives of 1.5 to 2 million children under the age of 5 each year. Children in resource-limited areas around the world 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 may be helpful as adjunctive therapy for acute pediatric diarrhea. The results of the present study support the conclusions of a comprehensive systematic review and meta-analysis conducted in 2014 by Feizizadeh et al. was published. The review, which analyzed 22 clinical trials, concluded thatSaccharomyces boulardiiused as adjunctive therapy, reduces the duration of acute pediatric diarrhea.²A 2015 systematic review and meta-analysis by Ahmadi et al., which analyzed 14 articles, concluded that the duration of acute rotavirus diarrhea in children was reduced by the administration ofLactobacillus rhamnosusGG and other probiotics compared to control.³

In the future, clinical practice may be further guided by research focused on which strains and at what doses are most clinically effective.

Many of the studies to date have been placebo-controlled studies and not direct comparisons of different probiotics. We can now assume that probiotics are more effective than placebo in treating pediatric diarrhea. In the future, clinical practice may be further guided by research focused on which strains and at what doses are most clinically effective.

In the present study by Asmat et al.Saccharomyces boulardiiwas effective in more patients than lactic acid-producing probiotics for the treatment of acute pediatric diarrhea, with 45% having a reduction in diarrhea compared to 26%. The present study confirms the results of a study by Eren et al. from 2010, in which the comparison was madeSaccharomyces boulardiiincluded in yogurtLactobacillus bulgaricusandS thermophilesas adjunctive treatment for acute pediatric diarrhea. On day 3 of the study, 48.5% of participants were co-treatedSaccharomyces boulardiihad resolution of the diarrhea compared to 25.5% of those treatedLactobacillus bulgaricusandS thermophiles.⁴Both studies support the idea thatSaccharomyces boulardiishould be considered as the first-line probiotic for the complementary treatment of acute diarrhea.

In the present study, it was intriguing to find that the response to treatment was comparable between the two groups in the first 7 days (21% vs. 15%). There was no significant difference until days 7 to 13, when an additional 24% of participants in group A had resolution of diarrhea, versus only 11% in group B. This implies that treatment with probiotics and in particularSaccharomyces boulardiishould be considered for at least 2 weeks after the onset of acute diarrheal symptoms to achieve the potential therapeutic benefit.

Although not examined in this study, it would be interesting to see whether participants in both groups who received 2 weeks of treatment with oral rehydration, antibiotics and probiotics (representing 55% ofSaccharomyces boulardii-treated group A and 74% of group B) would have responded to longer treatment, higher doses or a more diverse mix of probiotic strains.

Given the public health impact of diarrheal disease, particularly in resource-limited countries, and the millions of children who die annually, the positive results of studies of probiotic therapy should prompt further research to demonstrate its effectivenessSaccharomyces boulardiiandLactobacillus rhamnosusGG and other promising varieties. Additionally, combining strains with known benefits for acute diarrhea may increase efficacy and provide a more foolproof way to achieve the highest response rate to treatment.

The present study had some areas of concern that warrant caution in interpreting the results. The methodology did not specify the exact probiotic products used in the study, who supplied them, how they were stored, whether they were tested for viability, or the number of colony forming units included in each dose. Additionally, the only description we have for the product used for Group B participants is “lactic acid producing probiotics” and not any specific strain of bacteria.

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

Also interesting was the decision to treat all participants with antibiotic therapy, which carries its own risks (e.g., antibiotic-associated diarrhea) and is not considered first-line treatment for diarrheal illnesses, which are usually of viral origin. There may be specific indications for antibiotic use not listed in the publication and related to the geographical area in which the study was conducted (Pakistan).¹

Finally, the study design comparing 2 complementary probiotic interventions could potentially have been improved by the addition of a placebo control arm and a probiotic combination arm.

Despite its shortcomings, the paper still deserves consideration given the ever-growing body of evidence supporting a wide range of therapeutic uses for probiotics. At best, probiotics may provide symptom benefit with a very low risk of side effects, which is always something worth pursuing.