Cochrane review: Probiotics for the prevention of pediatric antibiotic-associated diarrhea

Authors

  • BC Johnston,

  • AL Supina,

  • M Ospina,

  • S Vohra

    Associate Professor, Corresponding author
    1. Department of Pediatrics, University of Alberta, Aberhart Centre #1, Room 8213, 11402 University Avenue NW, Edmonton, Alberta, T6G 2J3, CANADA
    • Department of Pediatrics, University of Alberta, Aberhart Centre #1, Room 8213, 11402 University Avenue NW, Edmonton, Alberta, T6G 2J3, CANADA
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Abstract

Background

Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population.

Objectives

To assess the efficacy and adverse effects of probiotics (any specified strain or dose) for the prevention of antibiotic-associated diarrhea in children.

To assess adverse events associated with the use of probiotics when co-administered with antibiotics in children.

Search strategy

MEDLINE, EMBASE, CENTRAL, CINAHL , AMED, and the Web of Science (inception to August 2006) were searched along with specialized registers including the Cochrane IBD/FBD Review Group, CISCOM, Chalmers PedCAM Research Register and trial registries from inception to 2005. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were hand searched.

Selection criteria

Randomized, parallel, controlled (placebo, active, or no treatment) trials comparing co-administered probiotics with antibiotics for the prevention of diarrhea secondary to antibiotic use in children (0 to 18 years).

Data collection and analysis

Methodological quality assessment and data extraction were conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of diarrhea, adverse events) were combined using pooled relative risks, and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. Adverse events were summarized using risk difference. For overall pooled results on the incidence of diarrhea, a priori sensitivity analyses included per protocol versus intention to treat, random versus fixed effects, and methodological quality criterion. Subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent.

Main results

Ten studies met the inclusion criteria. Trials included treatment with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination. Six studies used a single strain probiotic agent and four combined two probiotic strains.

The per protocol analysis for 9/10 trials reporting on the incidence of diarrhea show statistically significant results favouring probiotics over active/non active controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of ten trials monitored for adverse events (n = 647); none reported a serious adverse event.

Authors' conclusions

Probiotics show promise for the prevention of pediatric AAD. While per protocol analysis yields treatment effect estimates that are both statistically and clinically significant, as does analysis of high quality studies, the estimate from the intention to treat analysis was not statistically significant. Future studies should involve probiotic strains and doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day). Research done to date does not permit determination of the effect of age (e.g., infant versus older children) or antibiotic duration (e.g., 5 days versus 10 days). Future trials would benefit from a validated primary outcome measure for antibiotic-associated diarrhea that is sensitive to change and reflects what treatment effect clinicians, parents, and children consider important. The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD.

Plain language summary

It is premature to routinely recommend probiotics for the prevention of pediatric antibiotic-associated diarrhea (AAD)

Studies of probiotics for the prevention of pediatric AAD. Ten studies were reviewed and provide the best evidence we have. Study quality was mostly good overall. The studies tested 1986 children (aged 0 to 18 years) who were receiving probiotics co-administered with antibiotics to prevent AAD. The subjects received probiotics (Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination), placebo (fake pills), other treatments thought to prevent AAD (i.e. diosmectite or infant formula) or no treatment. The studies were short term and ranged in length from 15 days to 3 months.

What is AAD and could probiotics work to prevent AAD? AAD occurs when antibiotics disturb the natural balance of "good" and "bad" bacteria in the intestinal tract causing harmful bacteria to sometimes multiply beyond their normal numbers. The symptoms of AAD may include frequent watery bowel movements and crampy abdominal pain. Probiotics are dietary supplements containing potentially beneficial bacteria or yeast. Probiotics are thought to restore the natural balance of bacteria in the intestinal tract.

What did the studies show? An analysis that included only patients who completed the studies showed that probiotics may be effective for preventing AAD. However, a more conservative analysis that counted study drop-outs as treatment failures did not show any differences between probiotic and comparison groups.

How safe are probiotics? Probiotics were generally well tolerated and side effects occurred infrequently.

What is the bottom line? Although current data are promising, there is insufficient evidence to routinely recommend the use of probiotics for the prevention of pediatric AAD.

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