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Digestive Diseases and Sciences, Vol. 48, No. 10 (October 2003), pp. 2077–2082 (
A Randomized Trial of Yogurt for Prevention
of Antibiotic-Associated Diarrhea
RIPUDAMAN S. BENIWAL, MD,* VINCENT C. ARENA, PhD,† LENO THOMAS, MD,‡ SUDHIR NARLA,
MD,§ THOMAS F. IMPERIALE, MD,* RAUF A. CHAUDHRY, MD,‡ and USMAN A. AHMAD, MD‡
Antibiotic-associated diarrhea (AAD) is the most common adverse effect of antibiotic therapy. Our
aim was to determine the effectiveness of a dietary supplement of yogurt for prevention of AAD.
Two hundred two hospitalized patients receiving oral or intravenous antibiotics were randomized to
receive or not receive a dietary yogurt supplement, consisting of 227 grams of commercial yogurt,
and followed for 8 days. Mean age of the study group was 70 years and 43% were male. Compliance
and 8-day follow-up were 85% and 91%, respectively. Patients receiving yogurt reported less fre-
quent diarrhea (12% vs 24%; P = 0.04), and signiﬁcantly less total diarrheal days (23 vs 60). The
cumulative proportions of patients without diarrhea were signiﬁcantly different (P = 0.02) between
patients receiving and not receiving yogurt. For conclusion, dietary supplementation with yogurt is
a simple, effective, and safe treatment that decreases the incidence and duration of AAD.
KEY WORDS: effectiveness; yogurt; dietary intervention; biotherapeutics; prophylaxis; antibiotic-associated diarrhea.
Antibiotic-associated diarrhea (AAD) is the most com-
mon adverse effect of antimicrobial therapy, occurring in
5–39% of patients (1–3). AAD ranges in severity from
a mild increase in stool frequency to debilitating, life-
threatening diarrhea. Two major forms of AAD have been
identiﬁed. One form is enigmatic as no pathogen is identi-
ﬁed. Typical clinical features include onset during antibi-
otic exposure, stool frequency that is dose-related, resolu-
tion upon discontinuation of the implicated drug, absence
of local or systemic inﬂammation, and a usually benign
course. Pathogenesis may be related to altered short-chain
fatty acids in the intestine, functional disturbance of car-
bohydrate and bileacid metabolism due to alteration of the
Manuscript received July 9, 2002; accepted January 16, 2003.
From the *Division of Gastroenterology and Hepatology, Department
of Medicine, Indiana University School of Medicine and Roudebush
VA Medical Center, Indianapolis, Indiana; †Department of Biostatistics,
Graduate School of Public Health, University of Pittsburgh, Pittsburgh,
Pennsylvania; and ‡Department of Medicine and §Division of Gas-
troenterology, Department of Medicine, UPMC-McKeesport Hospital,
McKeesport, Pennsylvania, USA.
Address for reprint requests: Dr. Ripudaman S. Beniwal, Health
Services Research and Development Roudebush VA Medical Center
(11H) 1481 W. 10th Street Indianapolis, Indiana 46202, USA; e-mail:
microﬂora, or toxic effects on the intestinal mucosa, and
pharmacological effect on motility. The second form is
Clostridium difﬁcile-associated diarrhea, which accounts
for 10–20% of AAD. Symptoms may persist for months,
and endoscopic ﬁndings range from normal mucosa to
severe colitis, with the most characteristic lesion being
pseudomembranous colitis. Occasionally other bacteria
may be implicated. Pathogenesis of AAD may be related
to loss of the resistance provided by normal colonic ﬂora,
as the antibiotics suppress the intestinal microﬂora that
hold proliferation of C. difﬁcile in check (4, 5).
In a study from the United Kingdom, the economic im-
pact of AAD in a community hospital was $638,880 with
2100 lost bed days per year (6). AAD was associated with
a ﬁvefold increased risk of other nosocomial infections
and a threefold increase in mortality (7).
Until recently, biotherapeutics has been a neglected
modality in the treatment and prevention of selected in-
testinal infections. Placebo-controlled studies have shown
that biotherapeutic agents have been used successfully to
prevent AAD (8). However, none of these studies eval-
uated the effectiveness of commercially available yogurt
with live active cultures for the prevention of AAD.
Digestive Diseases and Sciences, Vol. 48, No. 10 (October 2003)
2003 Plenum Publishing Corporation