Vol.3, No.2, 110-1 15 (2011) Health
doi:10.4236/health.2011.32020
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Efficacy of a synbiotic chewable tablet in the prevention
of antibiotic-associated diarrhea
Charles Spielholz
Nutraceutical Medical Research, 445 Hamilton Avenue, Suite 1102, White Plains, New York, 10601. USA.
Received 4 January 2011; revised 24 January 2011; accepted 27 January 2011
ABSTRACT
Infection by Clostridium difficile, a complication
of treatment with antibiotics, causes antibiotic-
associated diarrhea (AAD) and can lead to coli-
tis and pseudomembranous colitis. Incidence of
C. difficile infection is increasing among the
elderly undergoing antibiotics therapy confined
to health care facilities, conditions that are ex-
pensive to treat, decrease the quality of life and
are life threatening. Use of probiotics has been
proposed as a method to decrease the inci-
dence of AAD in health care facilities. To exam-
ine the efficacy of using probiotics, 120 nursing
home residents undergoing antibiotic therapy
were provided w ith a synbiotic tablet containing
two probiotics, Saccharomyces boulardii and
Bacillus coagulans, and a prebiotic, fructooli-
gosaccharide. Residents were evaluated retro-
spectively for AAD and C. difficile infection. It
was found that 95% of residents treated with
antibiotics and taking the synbiotic tablet were
free of AAD. More than 97% of the residents did
not become infected with C. difficile. No adv erse
effects were reported. Minor side effects, gas-
trointestinal up set and nausea, were reported by
less than 6% of the residents. The cause of the
minor side effects was not know n. Only 2.5% of
the residents stopp ed taking the synbiotic t ablet
because of the gastrointestinal upset. These
Results suggest that use of the synbiotic tablet
prevents AAD and C. difficile infection in nurs-
ing home residents undergoing antibiotic ther-
apy. It is concluded that this synbiotic tablet
provides an easy to administer and safe ap-
proach to controlling AAD and C. difficile infec-
tion in residents in nursing homes.
Keywords: Synbiotic; Saccharomyces Boulardii;
Bacillus Coagulans; Antibiotic-Associated Diarrhea;
Clostridium Difficile
1. INTRODUCTION
Antibiotics have significantly decreased mortality re-
sulting from infectious disease and increased the success
rates of many medical procedures such as surgery.
However, use of an tib iotics also causes significant losses
to the population of beneficial microbiota residing in the
digestive tract. The digestive tract is the front line of
defense against infection, representing a significant por-
tion of the total immune system [1]. Loss of native pop-
ulations of beneficial microbiota exposes the intestinal
mucosa and allows non-beneficial and pathological spe-
cies, including those that are antibiotic-resistant, to po-
pulate the intestine [2 ,3]. This results in a variety of bio-
logical changes in the digestive tract including changes
in immune function, inflammatory response and normal
metabolism [4]. Such changes increase susceptibility to
antibiotic-associated diarrhea (AAD) and antibiotic-
resistant infectious diseases [2].
Chronic use of broad-spectrum antibiotics in elderly
residents in health care facilities, such as nursing homes,
long-term care facilities, and hospitals, is leading to a
serious increase in the incidence of AAD [5,6]. AAD
occurs in 25% to 50% of residen ts taking antibiotic [7 ,8].
Clostridium difficile, a bacterial, spore-forming, anaero-
bic species that infects the human digestive tract, is re-
sistant to many commonly used antibiotics and is the
cause of C. difficile-associated diarrhea (CDAD). CDAD
represents 15% to 25% of all AAD occurring in health
care facilities [8,9]. C. difficile is the cause of approxi-
mately half of all cases of antibiotic-associated colitis
and almost all cases of pseudomembranous colitis, a life
threatening inflammation of the colon [9,11]. There are
now over 250,000 C. difficile infections requiring hospi-
talization in the United States each year [10] causing an
estimated 15,000 to 30,000 deaths each year. Nationally,
the cost of treating C. difficile infections is greater than
$1 billion per year [4].

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Treatment of C. difficile infection requires discon-
tinuation of antibiotic therapy, if appropriate, intrave-
nous fluids and administration of either metronidazole or
vancomycin [13-16]. Reinfection occurs in up to 30% of
those successfully treated [18,19]. Furthermore, use of
metronidazole or vancomycin contributes to the increase
in antibiotic resistant species [17,19]. Therefore, sup-
plemental and alternate methods using probiotics in the
treatment and prevention of C. difficile infection have
been proposed [20,21]. The idea behind administration
of probiotics is to replace the normal population of
beneficial microbes that are lost from the digestive tract
during antibiotic treatment [21]. Probiotic microbes sti-
mulate the immune system of the gut and suppress the
growth of pathological species [2,3].
In this report, the results of a retrospective analysis of
residents in nursing homes undergoing treatment with
antibiotics and taking a chewable synbiotic tablet as an
adjunctive preventative of AAD are presented. The syn-
biotic tablet contained the nonpathogenic yeast Sac-
charomyces boulardii, the bacteria Bacillus coagulans,
and a prebiotic, fructooligosaccharide. The purpose of
this retrospective study was to analyze and understand
the feasibility of administering a synbiotic tablet to resi-
dents in a nursing home environment, analyze the poten-
tial efficacy with regard to AAD, C. difficile infection,
and CDAD and to define any safety and tolerability is-
sues.
2. METHODS
Residents in 17 nursing homes receiving antibiotic
treatment and taking the synbiotic tablet as part of their
standard of care from September 2009 to November
2009 were evaluated retrospectively for the presence of
AAD and C. difficile infection. The resident population
analyzed in this study consisted of 120 people. There
were 77 females representing 64.2% of the resident pop-
ulation, and 43 males representing 35.8% of the study
population. The residents ranged in age from 40 to 96
years with an average age of 80  10 years (Table 1).
Twenty six of the residents, representing 20.8% of the
study population, had a prior history of infection with C.
difficile, and 82 of the residents, representing 68.3% of
the population, d id not have a pr ior history of C. difficile
infection. The C. difficile history of 15 of the 120 resi-
dents, 12.5% of the study population, was not known
(Table 1).
The synbiotic tablet was in the form of a chewable
tablet containing two probiotics and one prebiotic. The
two probiotics were 7.5 b illion colon y forming un its (cfu )
of the yeast Saccharomyces boulardii and 1 billion cfu
of the ba cteria Bacillus coagulans. The prebiotic present
in the tablet was 500 mg of fructooligosaccharide. Resi-
Table 1. Demographics of the study population.
Study Population n = 120
Gender n (%)
Female 77 (64.2%)
Male 43 (35.8%)
Age years
A verage Age 80  10
Age Range 40-96
Prior C. difficile History n (%)
No Prior History 82 (68.3%)
Known Prior History 25 (20.8%)
Prior History Not Known 15 (12.5%)
dents were started on the synbiotic tablet shortly after
beginning treatment with an antibiotic. The synbiotic
tablet was given twice a day. Administration of the syn-
biotic tablet continued for two weeks after antibiotic
treatment was completed at which time residents were
evaluated for the presence of AAD and C. difficile infec-
tion. Demographic data included the sex and age of each
resident and prior medical history with regard to C. diffi-
cile infection. In additio n, all adverse events, sid e effects,
resident compliance, and ease of administration with
regard to taking the synbiotic tablet were noted. All data
were obtained from resident records through a nurse
employed by each nursing home using a questionnaire.
Residents were not known by name but were assigned a
code to protect their specific identity and privacy.
Statistical analysis of all numerical results was con-
ducted by calculating the average and standard devia-
tion.
3. Results
A total of 128 nursing home residents being adminis-
tered antibiotics were given a chewable synbiotic tablet
twice a day from September, 2009 to November, 2009.
Of the 128 residents offered the synbiotic tablet, 120
were evaluated for the purpose of this study and consti-
tuted the study population. Eight residents were not eva-
luated because the data received from the nursing home
was incomplete.
Most residents started the synbiotic regimen within 3
to 4 days after beginning antibiotic treatment. The aver-
age delay between initial treatment with antibiotics and
the start of ingestion of the synbiotic tablet was 2  4
days. Slightly more than one-half of the 120 residents,
64, began taking the synbiotic tablet immediately after
beginning antibiotic treatment (that is, beginning at 0
days).

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Residents were evaluated for the presence of AAD
and C. difficile infection 2 weeks after the completio n of
antibiotic treatment. During this 2-week period, residents
were maintained on the synbiotic tablet. The results of
the evaluation showed that 95% of the residents in the
study population remained free of AAD while taking the
synbiotic tablet (Ta ble 2). Only 6 of the 120 residents,
representing 5% of the study population, suffered from
AAD (Table 2). More than 98% of the residents did not
succumb to a C. difficile infection while taking the syn-
biotic tablet (Table 2). Two residents, representing 1.7%
of the study population, tested positive for the presence
of C. difficile (Table 2). Only 1 of these 2 residents,
which is less than 1% of the study population, suffered
from AAD and was classified as having CDAD (Table
2).
Clinicians found that the synbiotic tablet was easy to
administer (Table 3). The tablet was easy to administer
to 116 of the 120 residents, 96.7% of the study popula-
tion.
Resident compliance with taking the synbiotic tablet
was very high and is summarized in Table 3. Of th e 120
residents in the study population, 113, representing
94.2% of the study population, complied with taking the
synbiotic tablet for the duration of the study period.
There were three reasons that 8 residents did not comply
with taking the synbiotic tablet. Two of those residents,
1.7% of the study population, refused the synbiotic tablet.
Of those 2 residents, one had been diagnosed with de-
mentia which might explain the refusal. The reason the
second resident refused the synbiotic tablet could not be
ascertained. Three residents, 2.5% of the study popula-
tion, stopped taking the tablet because they were dis-
charged from the nursing home: one resident was dis-
charged to another facility, one resident was discharged
to a hospital, and one resident was able to return home.
There was no relationship of using the synbiotic tablet
and being discharged from the nursing home. Finally, 3
residents, 2.5% of the study population, discontinued use
of the synbiotic tablet because they experienced gastro-
intestinal difficulties as presented below.
There were no reports of serious adverse reactions
occurring in any of the residents taking the synbiotic
tablet (Table 3). In ad dition, 94% of the residents taking
the synbiotic tablet did not report any minor side effects
of any kind (Table 3). Minor side effects, all gastrointes-
tinal in nature, were reported by 7 residents representing
only 5.8% of the study population. Three of these resi-
dents, 2.5% o f the stud y population, experien ced naus ea.
The nausea had no effect on compliance of resident’s
taking the synbiotic tablet. Four of the residents, 3.3% of
the resident population, experienced gastrointestinal up-
set while taking the synbiotic tablet, 3 of whom were dis-
continued taking the synbiotic tablet as described above.
Table 2. Ef ficacy of the s ynbiotic tablet.
Study Population n = 120
Antibiotic-Associated Diarrhea AAD n (%)
Residents Free of AAD 114 (95%)
Residents With AAD 6 (5%)
C. difficile Infection n (%)
Residents Free of C. difficile infection 118 (98.3%)
Residents With C. difficile infection 2 (1.7%)
CDAD n (%)
Residents Free of CDAD 119 (99.2%)
Residents With CDAD 1 (0.08%)
Table 3. Compliance, adverse reactions and minor side effects of
synbiotic table.
Study Population n = 120
Compliance n (%)
Residents Complying with Tablet Schedule 112 (93.3%)
Residents Unable to Comply with Tablet Schedule 8 (6.6%)
Ease of Administration n (%)
Clinician Indicated Tablet was Easy to Admi nister 116 (96.7%)
Clinician Indicated Tablet was Not Easy to
Administer 4 (3.3%)
Adverse Reactions n (%)
Reports of Adverse Reactions 0 (0%)
Minor Side Effects n (%)
No Minor Side Effects 113 (94.2%)
Reported Minor Side Effects, Continued on Tablet 4 (3.3%)
Reported Minor Side Effects, Discontinued Tablet 3 (2.5%)
Therefore, only 3 residents representing 2.5% of the
study population experienced a side effect that suggested
they should stop taking the synbiotic tablet, strongly
indicating that greater than 97% of the residents had no
side effects or adverse reactions that would prevent use
of the synbiotic tablet.
4. Discussion
The retrospective data presen ted in this report suggest
that the synbiotic tablet de creased the incidence of AAD,
C. difficile infection, and CDAD relative to outcomes
expected if the population had not taken the tablet. The
incidence of AAD in the study population was 5% which
was 5-fold lower than the typical literature value of 25%
for those not given a synbiotic tablet [5,6]. Less than 2%

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of the study population was infected with C. difficile,
which is 4- to 16-fold lower than the expected 8% to
33% incidence of infection observed in health care fa-
cilities [22]. Less than 1% of the study population was
afflicted with CDAD, which is as much 15-fold lower
than the predicted rates of CDAD for residents in health
care facilities.
The low incidence of C. difficile infection observed in
the study population is also notable because it is at least
60% lower than the incidence expected from recurring
infections. Of the residents in the study population, ap-
proximately 21% had a prior history of C. difficile infec-
tion. Based on recurrence rate of 25% [7,17,22], more
than 5% of the study population would have been ex-
pected to present a C. difficile infection; however only
1.7% of the study population presented a C. difficile in-
fection, indicating that the synbiotic tablet suppressed C.
difficile infection by 66%.
The data presented in this report agree well with pr ior
studies using probiotic or synbiotic supplements. In this
report, the synbiotic tablet prevented AAD, C. difficile
infection, and CDAD by an estimated 75% or more rela-
tive to expected values. Reported clinical trials have
shown that probiotic supplements containing S. boulardii
or B. coagulans decreased levels of AAD by 50% to
85% [23,25] and CDAD by 45% to 85% [26-28]. Me-
ta-analysis of multiple clinical trials has shown that pro-
biotics decrease ADD and CDAD by 40% to 60%
[29,30].
The mechanisms by which the components of the
synbiotic tablet used in this study, S. boulardii, B. co-
agulans, and fructooligosaccharide, function to reduce
AAD, C. difficile infection, and CDAD have begun to be
elucidated. Each of the components of the synbiotic tab-
let appear to inhibit AAD, C. difficile infection, and
CDAD through different mechanisms. Studies have
shown that S. boulardii, can up-regulate IgA expression
against C. difficile toxin A [31,32]. S. boulardii may a ls o
inhibit C. difficile toxin directly [33-35]. Furthermore, S.
boulardii, has been shown to inhibit inflammatory sig-
naling pathways which may result in decreased damage
to the digestive tract by pathological species [36,37].
In combination with fructooligosaccharide, B. coagu-
lans has been shown to have properties that inhibit spe-
cies that cause AAD [38]. Fructooligosaccharide has
been shown to increase the growth of beneficial bacteria
such as bifidobacteria [39]. Bifidobacteria cause an in-
crease in short-chain fatty acid concentration and a de-
crease in the pH in the colon which results in condition s
that are not conducive to the growth of certain patho-
genic organisms. This may help restore colonization
resistance in the digestive tract [40,41]. Use of the syn-
biotic tablet in this study containing components that
function through different mechanisms increases the
probability of success.
No serious adverse reactions were reported while any
of the residents were taking the synbiotic tablet. Minor
side effects involved nausea or gastrointestinal upset. It
is not clear that the synbiotic tablet was the actual cause
of the nausea or gastrointestinal upset. The synbiotic
tablet was easy to administer with clinicians finding that
nearly 97% of the residents had no difficulty ingesting
the tablet. Resident compliance with tak ing the synbiotic
tablet was very high, with over 93% of residents using
the tablet as directed, indicating that the synbiotic tablet
was well tolerated by the study population.
There are limitations regarding the interpretation of
the results of this retrospectiv e study. The first is that th e
evaluations for AAD and the presence of C. difficile
were performed 2 weeks after the completion of antibi-
otic treatment. Although 80% of AAD cases occur 4 to 5
days after commencing antibiotic treatment, AAD can
occur up to 2 months after the initial treatment with an-
tibiotic. Therefore it is po ssible that some cases of AAD
and C. difficile infection were missed. Second, this stud y
did not examine a dose response. It is possible that an
increased dose of the synbiotic may further inhibit C.
difficile infections [5,42]. Finally, this study focused
solely on adult residents in nursing homes and not pa-
tients in hospitals. However, it is believed that the results
of this report will be applicable to settings other than
nursing homes.
The data presented in this report suggest that the syn-
biotic tablet can prevent AAD and C. difficile infection
in residents in a nursing home who receive antibiotics.
Development of an approach using synbiotics to replace
beneficial microbes lost in the digestive tract during an-
tibiotic treatment could significantly reduce the inci-
dence of antibiotic-resistant infections and the preva-
lence of AAD in health care facilities. Use of synbiotics
could also decrease reliance on antibiotics and thus re-
duce the rise in antibiotic-resistant pathogens. Further-
more, synbiotics could reduce the treatment costs asso-
ciated with residents suffering from antibiotic-resistant
infections and AAD. For example, it has been shown
that decreases in CDAD observed with ad ministration of
probiotics are associated with decreases in colitis [26].
The synbiotic tablet used in this study can be incorpo-
rated into the health care protocols of health care facili-
ties as an easy to administer, safe, acceptable, and easy
to tolerate approach to preventing AAD and C. difficile
infections.
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