Probiotic Use May Reduce the Risk of Antibiotic-Associated Diarrhea in Children

Resident Focus - Volume 12, Issue 7

Reference: Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827

Level 2 [mid-level] evidence

Antibiotics are a cornerstone of modern medical treatment for a variety of infections in both children and adults. Antibiotics were initially viewed as a panacea and used with little hesitation. However, antibiotic use has come under increasing scrutiny over the last several decades as the harms associated with these drugs become more apparent. While the devastation caused by antibiotic-resistant bacteria grab many of the headlines, the incidence of antibiotic-associated diarrhea (AAD) varies from 5% to 62% in cohort studies (Future Microbiology 2008;3(5):563, Digestive Diseases 1998;16(5):292) . The majority of those affected will suffer watery bowel movements, urgency, and crampy abdominal pain. However, some patients will suffer severe consequences from AAD including electrolyte disturbances, volume depletion, pseudomembranous colitis, toxic megacolon, and even death. Probiotics have been proposed as a mechanism to help restore a favorable microbial balance in the gut. Several meta-analyses appear to support the use of probiotics as an adjunct to antimicrobial therapy in adults, and a large number of both over-the-counter and prescription probiotic formulations have entered the marketplace (Therapeutic Advances in Gastroenterology. 2010;3(5):307-319). Important questions for consideration are whether or not probiotics reduce the risk of AAD in children and with what margin of safety?

A recent Cochrane review analyzed 23 randomized controlled trials comparing probiotics to placebo, active alternative prophylaxis, or no treatment for prevention of AAD in 3,938 children or adolescents (ages 0-18 years) receiving antibiotics. Probiotics studied included Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or Saccharomyces boulardii alone or in combination in preparations including yogurt, kefir, and capsules. There was significant clinical heterogeneity among included studies regarding the number of probiotic strains studied (1-10 strains; 11 of 23 trials studied only 1 strain), the dose of probiotic, and the definition of AAD. Outside of one high-quality trial comparing yogurt containing Lactobacillus rhamnosus GG, Lactobacillus acidophilus, and Bifidobacterium lactis, other trials had methodologic limitations including unclear allocation concealment and/or unclear blinding.

The incidence of AAD in patients receiving probiotics was 8% compared to 19% in the controls in a meta-analysis of 22 trials with 3,898 patients. Compared with controls, probiotics were associated with a decreased risk of AAD (risk ratio (RR) 0.46, 95% CI 0.35-0.61) with a number needed to treat (NNT) of 8-14. Probiotic doses of 5-40 billion colony-forming units (CFUs) per day were found to be more effective at preventing AAD than doses of

< 5 billion CFU/day. Individual products associated with reduced risk of AAD included Lactobacillus rhamnosus in analysis of 4 trials with 611 patients (RR 0.35, 95% CI 0.22-0.56, NNT 7-12) and Saccharomyces boulardii in analysis of 4 trials with 1,611 patients (RR 0.4, 95% CI 0.17-0.96, NNT 8-157). There was no significant difference in adverse events comparing probiotics to control in analysis of 16 trials with 2,455 patients. No serious adverse events attributable to probiotics were reported.

Based on this systematic review, adding probiotics to an antibiotic regimen in pediatric patients may reduce the risk of developing antibiotic-associated diarrhea. The potential harms of AAD, the relatively low NNT (8-14) when utilizing probiotic therapy, and the favorable safety profile of probiotics support consideration of this therapy for most pediatric patients undergoing antibiotic therapy.

For more information, see the

Probiotics to prevent antibiotic-associated diarrhea topic in Dynamed Plus. DynaMed users, see the Probiotics to prevent antibiotic-associated diarrhea topic in Dynamed Classic.

Dr. Jon Saks is a recent graduate of the UVA Family Medicine Residency Program. His interests include transitional care management and caring for refugee patients.Dr. Saks and his family now live in Roanoke, Virginia, where he will practice general Family Medicine at the Carilion Clinic.

Faculty contributions by Katharine C. DeGeorge, MD, MS.

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