Lack of an Effect of Lactobacillus reuteri DSM 17938 in Preventing Nosocomial Diarrhea in Children: A Randomized, Double-Blind, Placebo-Controlled Trial

doi:10.1016/j.jpeds.2011.12.049

The Journal of Pediatrics

Volume 161, Issue 1, July 2012, Pages 40-43.e1

https://doi.org/10.1016/j.jpeds.2011.12.049 Get rights and content

Objective

To evaluate the efficacy of administering Lactobacillus reuteri DSM 17938 for the prevention of nosocomial diarrhea.

Study design

Children (n = 106; aged 1-48 months) admitted to the hospital for reasons other than diarrhea were enrolled in a randomized, double-blind, placebo-controlled trial. They received L reuteri DSM 17938 at a dose of 10⁸ colony-forming units (n = 54) or a placebo (n = 52) orally, once daily, for the duration of the hospital stay.

Results

Data from all children were included in the final analysis. L reuteri DSM 17938 did not significantly affect the risk of developing nosocomial diarrhea, defined as 3 loose or watery stools per day in a 24-hour period that occurred >72 hours after admission (risk ratio 1.06, 95% CI 0.7-1.5) or rotavirus infection (1.04, 0.6-1.6). There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes (ie, incidence of rotavirus infection, incidence of diarrhea, duration of diarrhea, incidence of recurrent diarrhea, incidence of chronic diarrhea, length of hospital stay in days, and frequency of need for rehydration). No adverse events were reported.

Conclusion

In hospitalized children, the administration of L reuteri DSM 17938 compared with placebo had no effect on the overall incidence of nosocomial diarrhea, including rotavirus infection.

Section snippets

Methods

The standards from the guidelines of the Consolidated Standards of Reporting Trials were followed for this randomized controlled trial (RCT). This trial was registered at ClinicalTrials.gov (NCT01046656). The study was approved by the Ethics Committee of the Medical University of Warsaw. Parents were fully informed about the aims of the study, and informed consent was obtained from at least 1 parent.

This was a prospective, randomized, double-blind, placebo-controlled trial conducted in the

Results

The Figure (available at www.jpeds.com) is a flow diagram showing the subjects’ progression through the study. Of the 106 children who underwent randomization, 54 were assigned to the probiotic group and 52 were assigned to the placebo group. Baseline demographic and clinical characteristics did not differ between the 2 groups (Table I). The outcome measures are summarized in Table II. We found no difference between the study groups with respect to the incidence of nosocomial diarrhea. Of the

Discussion

This study provides evidence that in hospitalized children, the administration of L reuteri DSM 17938 at a dose 10⁸ CFU per day compared with placebo had no effect on the overall incidence of nosocomial diarrhea, including rotavirus infection.

The strengths of this study include adequate randomization, the use of a double-blind design, comprehensive follow-up, and the use of intention-to-treat analysis, all of which minimize the risk of bias. Considering the negative findings, one limitation of

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The health benefits of probiotics in children have been the subject of thorough research. Probiotics are supplements containing viable microorganisms that confer health benefits on the host. Beneficial effects of select probiotic strains for the management or prevention of select pediatric conditions have been extensively proven. The best documented efficacy of certain probiotics is for the treatment of acute gastroenteritis, for the prevention of antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and nosocomial diarrhea. Unfortunately, due to the different study designs, currently a broad consensus for the majority of indications, for specific strains, dosages, and treatment regimens is lacking. More well-designed, large, strain-specific, and dedicated dose–response studies are needed. However, some evidence to support the use of certain probiotics in select pediatric conditions is often available. In addition, the administration of probiotics only carries a low risk of adverse events and is generally well tolerated. The purpose of this chapter is to provide an overview of current available evidence on the specific efficacy of probiotics in select conditions to guide pediatricians in decision-making on the therapeutic or prophylactic use of probiotic strains in children, possibly also outside applicable directives. The use of probiotic strains without proven efficacy should not be considered.
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Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: a randomized clinical trial
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To assess the effectiveness of Lactobacillus reuteri DSM 17938 for the prevention of diarrhoea and antibiotic-associated diarrhoea (AAD) in children.
Hospitalized children who received antibiotics were assigned by a computer-generated list to receive L. reuteri (at 2 × 10⁸ CFU) or placebo, twice daily, for the duration of antibiotic treatment. Follow up was for 1 week after antibiotic cessation. The primary outcome measures were diarrhoea and AAD. Both were defined according to one of three definitions (i) three or more loose or watery stools per day for ≥48 h; (ii) three or more loose or watery stools per day for ≥24 h; or (iii) two or more loose or watery stools per day for ≥24 h. For AAD, it had to be diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea.
A total of 250 children were randomized and 247 were analysed (L. reuteri n = 123, placebo n = 124; median age 4 months). The occurrences of diarrhoea and AAD were similar in both groups, regardless of the definition used. Using the strictest definition (i.e. definition (i)), the occurrence of diarrhoea in the L. reuteri group was 25 (20%) compared with 16 (13%) in the placebo group (absolute risk reduction –0.07 (–0.17 to 0.02). The occurrence of AAD was 14 (11.4%) in the L. reuteri group compared with 8 (6.5%) in the placebo group (absolute risk reduction –0.05 (–0.13 to 0.02)). The groups were similar with respect to all secondary outcome measures, including adverse events.
Lactobacillus reuteri was not effective in the prevention of diarrhoea or AAD in children.
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Lactobacillus reuteri is a Gram-positive, rod-shaped lactic acid bacterium that is found in humans, animals, and fermented foods. In the last 30 years, strains of L. reuteri have increasingly been used in humans and animals as probiotics. This chapter reviews various aspects of L. reuteri including its use as a probiotic in humans, ecological and physiological properties of this species, and recent research investigating the mechanisms by which strains of this species beneficially impact health.
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: This study was funded by the Medical University of Warsaw, which received a donation from the manufacturer of L reuteri DSM 17938, BioGaia AB, Lund, Sweden. The manufacturer had no role in the conception, design, or conduct of the study, or in the analysis or interpretation of the data. The authors declare no conflicts of interest.

: Registered at ClinicalTrials.gov: NCT01046656.

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The Journal of Pediatrics

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

References (17)

CDC/NHSN surveillance definition of health careassociated infection and criteria for specific types of infections in the acute care setting

Am J Infect Control

Infection control in paediatrics

Lancet Infect Dis

Incidence of nosocomial rotavirus infections, symptomatic and asymptomatic, in breast-fed and non-breast-fed infants

J Hosp Infect

Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants

J Pediatr

Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus

Lancet

Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study

J Pediatr

Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research

J Nutr

European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe

J Pediatr Gastroenterol Nutr

Cited by (47)

Probiotics in pediatrics

Prophylactic use of probiotics for gastrointestinal disorders in children

Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: a randomized clinical trial

Lactobacillus reuteri

Intestinal microbiota and susceptibility to viral infections: Role of probiotics

A systematic review and meta-analysis: the therapeutic and preventive effect of Lactobacillus reuteri DSM 17,938 addition in children with diarrhea

Original ArticleLack of an Effect of Lactobacillus reuteri DSM 17938 in Preventing Nosocomial Diarrhea in Children: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

Am J Infect Control

Lancet Infect Dis

J Hosp Infect

J Pediatr

Lancet

J Pediatr

J Nutr

European Society for Paediatric Gastroenterology, Hepatology, and Nutrition/European Society for Paediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe

J Pediatr Gastroenterol Nutr

Original Article
Lack of an Effect of Lactobacillus reuteri DSM 17938 in Preventing Nosocomial Diarrhea in Children: A Randomized, Double-Blind, Placebo-Controlled Trial