Yogurt for Diarrhea

Abstract & Commentary

By Allan J. Wilke, MD Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of Medicine—Huntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study. This article originally appeared in the September 15, 2007 issue of Internal Medicine Alert. It was edited by Stephen Brunton, MD, and peer reviewed by Gerald Roberts, MD. Dr. Brunton is Clinical Professor of Medicine, Albert Einstein College of Medicine. Dr. Brunton is a consultant for Sanofi-Aventis, Ortho-McNeil, McNeil, Abbott, Novo Nordisk, Eli Lilly, Endo, EXACT Sciences, and AstraZeneca, and serves on the speaker's bureau for McNeil, Sanofi-Aventis, and Ortho McNeil. Dr. Roberts reports no financial relationship relevant to this field of study.

Synopsis: Patients receiving a probiotic yogurt drink were protected from antibiotic associated bacteria.

Source: Hickson M, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: Randomised double blind placebo controlled trial. BMJ. 2007;335:80.

In this randomized, double-blind, placebo-controlled study, Hickson and colleagues hypothesized that they could reduce the occurrence of antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) among hospitalized older patients taking antibiotics by feeding them a commercially available probiotic yogurt drink. They screened 1760 patients and, after exclusion, enrolled 135 (54% female, 89% white, average age 74 years). Exclusion criteria included diarrhea within a week of admission, antibiotic use up to 4 weeks before admission, conditions that might predispose to infection from the bacteria in the probiotic (eg, immunosuppression), probiotic use before admission, and lactose intolerance. The two groups were balanced with regards to the usual demographic data, the number of antibiotics taken during hospitalization, the number of high-risk antibiotics (aminopenicillins and cephalosporins) taken, and the conditions requiring antibiotics (respiratory tract infections, surgical prophylaxis, and urinary tract infections accounting for almost all). The primary end point was the development of diarrhea (> 2 liquid stools daily for ³ 3 days). The secondary end point was C. difficile infection (diarrhea plus detection of toxins A and/or B). The intervention group received 100 mL (3 ounces) of a yogurt drink containing Lactobacillus casei, Streptococcus thermophilus, and Lactobacillus bulgaricus twice daily. Controls similarly received a sterile milkshake. Subjects were enrolled within 48 hours of receiving an antibiotic, at which time baseline data and a stool sample to rule out C. difficile were obtained and the randomized drink prescribed. The drinks were continued for one week after finishing the course of antibiotics, including those patients who were discharged home on antibiotics. No adverse effects were noted for either drink. Analysis was by intention-to-treat. In the yogurt group, 12% of patients developed AAD vs 34% in the milkshake group (number-needed-to-treat [NNT] 5). None of the yogurt group developed CDAD; 17% in the milkshake group did (NNT 6). Interestingly, one patient in both groups tested positive for C. difficile toxin before antibiotics were administered, but neither developed diarrhea. Length of stay did not differ significantly.

Commentary

Previous studies have found a beneficial effect of Saccharomyces boulardii on diarrhea in children taking antibiotics.1 A more recent Cochrane review of pediatric probiotic use concluded, "The current data are promising, but it is premature to routinely recommend probiotics for the prevention of pediatric AAD."2 A meta-analysis written by one of the co-authors of this study found support for the use of S. boulardii and lactobacilli, but suggested that "a further large trial in which probiotics are used as preventive agents should look at the costs of and need for routine use of these agents."3 Another meta-analysis found that "three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for [Clostridium difficile disease]."4

The yogurt product in question was Actimel®, marketed in the US as DanActive®. The manufacturer helped fund the study. At my local supermarket it is sold in a four-pack at $2.49. That's $1.25 per day if given as it was in this study. Some physicians might bristle at its marketing, which emphasizes "helps strengthen your body's defenses" (http://www.danactive.com/). What applies to sick patients taking antibiotics does not necessarily translate into a panacea for the whole population.

A few questions: would a different probiotic product work as well? Do we need all three bacterial strains or would one or two be enough? What is the role of S. boulardii? Are there differences between adults and children in the prevention of ADD? Despite its limitations (huge exclusion rate, difficulty in blinding, predominantly elderly white population), this is an important study. If its results are confirmed in other studies, it could save the health system a lot of money. Unlike some other interventions, the savings would not come from shorter lengths of stay, but from the costs of treating AAD-vancomycin, which isn't cheap. A 10-day oral course runs about $2,000. If, on the other hand, it was shown that the yogurt drink reduced hospitalizations for AAD when given to outpatients starting a course of antibiotics, then we'd be talking real money. Three ounces of prevention is worth a pound of cure.

References

1. Kotowska M, et al. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea in children: A randomized double-blind placebo-controlled trial. Aliment Pharmacol Ther. 2005;21:583-590.

2. Johnston BC, et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2007;(2):CD004827.

3. D'Souza AL, et al. Probiotics in the prevention of antibiotic associated diarrhea: Meta-analysis. BMJ. 2002;324:1361.

4. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol. 2006;101:812-822.