Probiotics for the Control of Clostridium difficile

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Probiotics for the Control of Clostridium difficile
By: Charles Spielholz, Ph.D.
Abstract: Clostridium difficile is a bacterium that can cause serious infections of the human
intestine. Resistant to many commonly used antibiotics, C. difficile is transferred from patient-
to-patient by an oral-fecal route. Infection of susceptible people by C. difficile is on the rise in
hospitals, nursing homes, and long-term care facilities. C. difficile gains a foothold in the
intestine while patients are treated with antibiotics that kill both pathogenic bacteria and the
natural population of harmless bacteria residing in the intestines. Preliminary clinical
trials indicate probiotics may help prevent C. difficile infections in hospitals and similar settings.
However, additional clinical trials are required in order to establish treatment protocols.
Clostridium difficile is a gram positive, difficile infection can also cause a more serious
spore forming anaerobic bacillus that causes condition, pseudomembranous colitis, a life
intestinal disease in humans. The bacteria attain threatening inflammation of the colon (large
a foothold in the human intestinal tract when intestine). C. difficile is responsible for
populations of bacteria that are part of the approximately 25% of the AAD cases in the
normal flora and fauna of the digestive tract are United States. It is also responsible for at least
compromised by factors such as antibiotic use. half of all the cases of antibiotic-associated
C. difficile infection is a significant cause of colitis and probably all of the cases of
antibiotic-associated diarrhea (AAD). C. pseudomembranous colitis (1, 2). The incidence
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NMR News: Volume 3, Issue 5, May 2010
of C. difficile infections has been increasing vancomycin). Such an approach greatly
dramatically over the past decade (2, 3). Up to attenuates the population of C. difficile and stops
20% of individuals with C. difficile infections the infection. However this approach does not
die because of the infection (4). The bacteria are replace the natural population of microbiota that
generally transferred by an oral-fecal route. populated the digestive tract before antibiotic
treatment. Lack of natural populations of native
In addition to antibiotic use, risk factors
microbiota appears to play a role in making an
for intestinal infections by C. difficile include
individual susceptible to recurrence of C.
aging, hospitalizations, surgery, and stays in
difficile infections (5). Therefore, proposals to
long-term care facilities. Diabetics and those
add microbiota back to the digestive tract have
taking medications to suppress the immune
been put forward and have been tested in
system are also at increased risk for C. difficile
preliminary clinical trials. In addition, there are
infections. Elderly people, who are at increased
reports of C. difficile resistance to metronidazole
risk for surgery, diabetes, injury, infections and
and vancomycin. Such reports strongly indicate a
who are more likely to receive antibiotic
need to develop additional approaches to treating
treatment and to live in long-term care facilities,
this infection.
are particularly prone to C. difficile infection,
AAD and pseudomembranous colitis. One approach to adding microbiota back
to the digestive tract is to simply ingest
Standard treatment of C. difficile
probiotics. Probiotics are live microorganisms
generally involves replacement of the antibiotics
that, when fed to a host organism, confer a health
in use with antibiotics that have activity against
benefit. Probiotics generally consist of yeast
C. difficile (the antibiotics in most common use
and/or bacteria and can be administered through
for this purpose are metronidzole and
a functional food. Probiotics can also be
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NMR News: Volume 3, Issue 5, May 2010
administered in the form of supplements or tested for their potential in the prevention and
suppositories. Foods like yogurt are well known treatment of C. difficile infections (6, 7). For
sources of probiotics. It is always critical that probiotics composed of bacterial species, a small
the specific species and strain of probiotic be number of reports indicate that probiotics are
matched to the desired effect or condition. The potentially useful in decreasing the potential for
best species and strains of probiotics for specific acquiring a C. difficile infection while confined
conditions can only be determined through well in a hospital or similar institution. Patients
designed clinical trials. admitted to a hospital free of C. difficile
infection and receiving combinations of bacterial
The literature contains a variety of
probiotics (Lactobacillus and Bifidobacterium)
reports regarding treatment of C. difficile
in a double-blind, placebo-controlled clinical
infections with probiotics. Generally, the reports
trial were less likely to test positive for C.
show that treatment of C. difficile infections with
difficile toxins then control patients receiving
probiotics can be useful. However, a clear, well
placebo (8). This observation indicated that
defined protocol for using probiotics to treat C.
administration of bacterial based probiotics could
difficile has not yet been established. A brief
be useful in preventing patients from developing
review of some of the reports in the medical
C. difficile infections in settings like hospitals or
literature will provide a basic understanding of
long-term care facilities. Unfortunately, the
the current status of use of probiotics for C.
results of this study were compromised by the
difficile infection.
low number of patients enrolled. An
Bacterial strains from the genus observational pilot study produced data that
Lactobacillus and Bifidobacterium and a yeast supported this conclusion (9); however that study
strain from the genus Saccharomyces have been was of limited value for generating strong
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conclusions because it did not include a placebo Use of Saccharomyces species and
control group. Another double-blind, placebo- strains as a probiotic for the prevention of C.
controlled clinical trial using an additional difficile infection has also been explored. In a
bacterial strain from the genus Steptococcus randomized clinical trial, patients with an active
showed that patients receiving the probiotic C. difficile infection who were treated with
combination were less likely to develop diarrhea Saccharomyces were less likely to experience a
in a hospital setting and were less likely to recurrence of the infection by nearly half relative
express C. difficile toxins (10). This study to placebo (13). Further examination of the data
provided further support for the idea that the showed that this difference was especially
administration of bacterial probiotics could play significant for those patients who had at least one
a role in the prevention of C. difficile infections prior C. difficile infection. In a separate double-
in hospitals or, by extension, long term care blind, placebo-controlled study, Saccharomyces
facilities. However, not all clinical trials using was shown to prevent recurrence of C. difficile
bacterial based probiotics have been unequivocal infections in patients on low dose antibiotic
(7, 11). Discrepancies in reports are probably treatment, but not patients on high does
due to the fact that different studies are antibiotic treatment (14). The medical literature
performed under different conditions with does not appear to contain any controlled clinical
different patient populations, different probiotics, trials using Saccharomyces for primary
and different end points (12). The results of prevention of C. difficile infections.
these clinical trials should allow for the planning
These results are very promising.
and development of well defined studies that
Providing functional foods to patients in either a
could lead to well defined treatment protocols.
hospital or long term care facility may be a very
easy and inexpensive method of preventing C.
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NMR News: Volume 3, Issue 5, May 2010
difficile infections. Treatment with probiotics with less dependence on antibiotics and
may also help to slow the rate of appearance of decreased risk of causing the evolution of
C. difficile strains that are resistant to antibiotics. additional antibiotic resistant forms of this
Additional clinical trials are needed to precisely pathogen.
define the type of patient that would most likely
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NMR News: Volume 3, Issue 5, May 2010
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