Use of Lactobacillus Rhamnosus in Children with Gastroenteritis

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Clinical Question

In children with gastroenteritis, would use of Lactobacillus rhamnosus improve severity of gastroenteritis symptoms compared to no use?

Bottom Line

Not recommended; children treated with Lactobacillus rhamnosus did not show more worsening to moderate-to-severe gastroenteritis compared to children who received placebo.

Major Points

Acute gastroenteritis develops in millions of children in the United States every year, and treatment with probiotics is common. However, data to support the use of probiotics in this population are limited. The clinical question was “In children with gastroenteritis, would the use of Lactobacillus rhamnosus improve outcomes compared to no use?” The study that was conducted was a prospective, randomized, double-blind trial involving children 3 months to 4 years of age with acute gastroenteritis who presented to one of 10 U.S. pediatric emergency departments. The participants received a 5-day course of Lactobacillus rhamnosus GG at a dose of 1×1010 colony-forming units twice daily or matching placebo. Follow-up surveys were conducted daily for 5 days and again 14 days after enrollment and 1 month after enrollment. The primary outcome was moderate-to-severe gastroenteritis, which was defined as an illness episode with a total score on the modified Vesikari scale of 9 or higher (scores range from 0 to 20, with higher scores indicating more severe disease), within 14 days after enrollment. Secondary outcomes included the duration and frequency of diarrhea and vomiting, the duration of day-care absenteeism, and the rate of household transmission. Among the 971 participants, 943 completed the trial. There were no significant differences between the L. rhamnosus GG group and the placebo group in the progression to moderate-to-severe gastroenteritis or increase in the Vesikari score. There was also no difference in the duration of diarrhea, duration of vomiting, day-care absenteeism, or in the rate of household transmission. Among preschool children with acute gastroenteritis, those who received a 5-day course of L. rhamnosus GG did not have better outcomes than those who received placebo

Guidelines

Some of the relevant guidelines relating to this study are; This guideline from the American Academy of Family Physicians talks about how acute gastroenteritis is defined:

  • Diarrheal disease of rapid onset
  • Possible nausea
  • Vomiting
  • Fever
  • Abdominal pain.

It involves increased stool frequency or altered stool consistency that is unrelated to chronic conditions. The guideline main key recommendations for practice included ways to stay hydrated[1]

Design

  • Trial Type: Prospective, randomized, double blind RCT
  • Number of patients randomized (N): 943
  • Experimental Arm: 468
  • Standard: 475
  • Setting: Pediatric Emergency Departments
  • Enrollment: 5 Days
  • Mean follow-up: Daily for 5 days and again 14 days after enrollment
  • Analysis: Intention-to-treat principle excluding side effects which were analyzed in the as-treated population


Population

Inclusion Criteria

  • Children 3 months to 4 years of age
  • A diagnosis of acute gastroenteritis (three or more episodes of watery stools per day, with or without vomiting)
  • Fewer than 7 days

Exclusion Criteria

  • Risk factors for bacteremia
  • Pancreatitis
  • Bilious emesis
  • Hematochezia
  • Allergies to L. rhamnosus GG or microcrystalline cellulose or a known allergy to erythromycin, clindamycin, and beta-lactam antibiotic agents
  • Language (if the caregiver did not speak English or Spanish)


Baseline Characteristics

  • Child between the ages of 3 months and 4 years
  • Diagnosis of acute gastroenteritis (greater than or equal to 3 episodes of watery stool per day)
  • Fewer than 7 days

Interventions

Participants received the first dose of L. rhamnosus GG or placebo orally in the ED. Caregivers received oral and written instructions for administering subsequent doses. The L. rhamnosus GG and placebo were identical in appearance, texture, and flavor. If vomiting occurred within 15 minutes after administration of the probiotic or placebo, the dose was repeated once.


Outcomes

Primary Outcomes Primary outcome: progression to moderate to severe gastroenteritis, total score >9 out of 20 on a modified Vesikari scale within 14 days of enrollment

  • 11.8% L. rhamnosus
  • 12.6% placebo
  • RR=0.96
  • 95% CI 0.68-1.35
  • p=0.83

Secondary Outcomes Secondary outcomes included: duration and frequency of diarrhea/vomiting, duration of absenteeism, rate of household transmission (symptomatic in previously asymptomatic)

  • Duration of diarrhea: 49.7 hours L. rhamnosus; 50.9 hours placebo; p=0.26
  • Duration of vomiting: 0 hours both; p=0.17
  • Day-care absenteeism: 2 days both; p=0.67
  • Rate of household transmission: 10.6% L. rhamnosus; 14.1%placebo; p=0.16

Subgroup Analysis

The effect of using Lactobacillus rhamnosus in children with gastroenteritis vs placebo showed no significant differences between the L. rhamnosus GG group and the placebo group in the duration of diarrhea (median, 49.7 hours in the L. rhamnosus GG group and 50.9 hours in the placebo group; P=0.26), duration of vomiting (median, 0 hours in both groups; P=0.17), or day-care absenteeism (median, 2 days in both groups; P=0.67) or in the rate of household transmission (10.6% and 14.1% in the two groups, respectively; P=0.16).

Adverse Events

There were no significant differences between the trial groups in the case of adverse events, with the exception of wheezing reported in 5 participants of the experimental arm of the study.

Criticisms

Participants were enrolled when research staff were available, however there was no data collection on eligible children who were missed due to presenting to the ED after hours or those whose caregivers chose not to participate. There was also a heavily reliance on parental reports as the source of adherence and symptom reports. Although chart reviews were conducted at each site to assess potentially missed healthcare visits that occurred after randomization, families may have sought care at another facility. Despite caregivers being instructed to keep trial medication refrigerated, it is possible that the medication was exposed to temperature extremes.

Funding

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • Emergency Medical Services for Children Program of the Maternal and Child Health Bureau
  • Health Resources and Services Administration
  • Washington University Biobank Core
  • National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health
  • iHealth which provided L. rhamnosus GG and placebo capsules in kind.
  • Dr. Freedman is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness.

Further Reading

  1. [1]
Hartman, Scott, et al. “Gastroenteritis in Children.” American Family Physician, 1 Feb. 2019, www.aafp.org/afp/2019/0201/p159.html.[Internet]

American Academy of Family Physicians