Saccharomyces boulardii in the prevention of antibiotic-associated
diarrhoea in children: a randomized double-blind placebo-controlled
M. KOTOWSKA, P. ALBRECHT & H. SZAJEWSKA
Department of Pediatric Gastroenterology and Nutrition, The Medical University of Warsaw, Warsaw, Poland
Accepted for publication 24 November 2004
Background: Co-treatment with Saccharomyces boulardii
appears to lower the risk of antibiotic-associated diar-
rhoea in adults receiving broad-spectrum antibiotics.
Aim: To determine whether S. boulardii prevents anti-
biotic-associated diarrhoea in children.
Methods: A total of 269 children (aged 6 months to
14 years) with otitis media and/or respiratory tract
infections were enrolled in a double-blind, randomized
placebo-controlled trial in which they received standard
antibiotic treatment plus 250 mg of S. boulardii (experi-
mental group, n ¼ 132) or a placebo (control group,
n ¼ 137) orally twice daily for the duration of antibiotic
treatment. Analyses were based on allocated treatment
and included data from 246 children.
Results: Patients receiving S. boulardii had a lower
prevalence of diarrhoea (‡3 loose or watery stools/day
for ‡48 h occurring during or up to 2 weeks after the
antibiotic therapy) than those receiving placebo [nine of
119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95%
confidence interval: 0.2–0.7]. S. boulardii also reduced
the risk of antibiotic-associated diarrhoea (diarrhoea
caused by Clostridium difficile or otherwise unexplained
diarrhoea) compared with
(3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95%
confidence interval: 0.07–0.5]. No adverse events were
Conclusion: This is the first randomized-controlled trial
evidence that S. boulardii effectively reduces the risk of
antibiotic-associated diarrhoea in children.
placebo [fourof 119
Antibiotic-associated diarrhoea (AAD) is defined as an
acute inflammation of the intestinal mucosa caused by
the administration of broad-spectrum antibiotics. The
bacterial agent most commonly associated with AAD is
Clostridium difficile.1However, when the normal faecal
Gram-negative organisms are absent, overgrowth by
staphylococci, yeasts and fungi has been implicated.2
The frequency of AAD depends on the definition of
diarrhoea, the inciting antimicrobial agents and host
factors. Almost all antibiotics, particularly those that act
on anaerobes, can cause diarrhoea, but the risk is
higher with aminopenicillins, a combination of amino-
penicillins and clavulanate, cephalosporins and clinda-
mycin.3, 4AAD occurs in approximately 5–30% of
patients between the initiation of therapy and up to
2 months after the end of treatment.1, 5, 6The incidence
of diarrhoea in children receiving broad-spectrum
antibiotics ranges from 11 to 40%.7, 8
Measures to prevent AAD include the use of probiotics,
which are live microbial food ingredients that are
beneficial to health.9Well-known probiotics include
lactobacilli, bifidobacteria and the yeast Saccharomyces
boulardii. The rationale for the use of probiotics in AAD
is based on the assumption that the key factor in the
Correspondence to: Dr H. Szajewska, Department of Paediatric Gastro-
enterology and Nutrition, The Medical University of Warsaw, 01-184
Warsaw, Dzialdowska 1, Poland.
Aliment Pharmacol Ther 2005; 21: 583–590.doi: 10.1111/j.1365-2036.2005.02356.x
? 2005 Blackwell Publishing Ltd
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? 2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 583–590