Running head: FECAL MICROBIOTA TRANSPLANTATION VERSUS 1

Fecal Microbiota Transplantation (FMT) Versus Antibiotic Therapy for the Treatment of

Recurrent Clostridium Difficile

Nicholas Travis

University of South Florida

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Abstract

Clinical Problem: Clostridium Difficile is the leading cause of gastroenteritis-associated deaths

in the United States, which is further complicated by a high rate of recurrence.

Objective: To determine if Fecal Microbiota Transplantation is more effective than traditional

treatments for Recurrent Clostridium Difficile. The educational databases utilized to access data

on the subject include Google Scholar, CINAHL, and EMBASE. Search terms included Fecal

Microbiota Transplantation, Clostridium Difficile, antibiotic treatment, and vancomycin.

Results: Clinical trials demonstrated not only the safety of Fecal Microbiota Transplantation, but

that it is more effective in the treatment of Recurrent Clostridium Difficile than antibiotics. It is

recommended that providers considered FMT when Clostridium Difficile Infections do not

respond to traditional treatments.

Conclusion: Fecal Microbiota Transplantation is more effective than antibiotics in the treatment

of Recurrent Clostridium Difficile. FMT is a safe alternative to antibiotic treatments, however

there are risks involved. More research must be done to determine the safest and most effective

rout of administration of the Fecal Microbiota.

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Fecal Microbiota Transplantation (FMT) Versus Antibiotic Therapy for the Treatment of

Recurrent Clostridium Difficile

Clostridium Difficile is the leading cause of gastroenteritis associated deaths in the

United States and even the most conservative sources report recurrence rates that are over 20%

(Lessa et al., 2015). In the last 10 years, the rates of Clostridium Difficile have significantly

increased, while the effectiveness of traditional treatments has steadily declined (Cammarota et

al., 2015). The use of Fecal Microbiota Transplantation (FMT) may be a safer and more effective

form of treatment for these patients. In patients with Clostridium Difficile, how does Fecal

Microbiota Transplantation (FMT) compare to antibiotic therapy on the resolution of infection

within 30 days?

Literature Search

Google Scholar, CINAHL, and EMBASE were utilized to locate Clinical Trials related to the use

of Fecal Microbiota Transplantation in the treatment of recurrent Clostridium Difficile. Search

terms included Fecal Microbiota Transplantation, Clostridium Difficile, antibiotic treatment, and

vancomycin.

Literature Review

Cammarota et al. (2015) conducted a study to test the hypothesis that donor fecal transplant

procedures are more effective than traditional vancomycin treatments for Clostridium difficile

infections. The study was an open label randomized control study. The sample population

comprised of 39 adult patients with a current Clostridium Difficile infection that has recurred

after at least one course of antibiotics. The participants were randomized into a control group

(n=19) that received vancomycin and an intervention group (n=20) that received a Fecal

Microbiota Transplant via colonoscopy. Results showed a significantly higher rate of

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Clostridium Difficile remission in the Fecal transplant group than the vancomycin group

(P<.0001). Strengths of the study include randomization of participants, similar baseline status

among participants, an appropriate control group, and valid/reliable instruments were utilized.

The major weakness of the study is that participants and providers were not blind to the study

group. This weakness is easily explained due to the inherent and obvious differences in

treatment.

Kelly et al. (2016) conducted a double blind randomized control trial to determine the

effectiveness and safety of donor Fecal Microbiota Transplants in the treatment of Clostridium

Difficile Infections. The sample population comprised of 46 adult patients with diarrhea and a

positive C. Diff test who had 3 or more documented recurrences and have attempted vancomycin

treatment for at least 10 days. The control group (n=24) received autologous fecal transplants via

colonoscopy and the intervention group (n=22) received donor fecal transplants via colonoscopy.

The results showed that those treated with donor stool were more likely to be clinically cured

than those treated with autologous stool (P=0.042). Strengths of the study include a double blind

randomized design, follow up assessments were preformed out to 6 months, and Fecal

microbiota analysis and questionnaires on symptoms were valid and reliable. Weaknesses of the

study include the exclusion of adults over the age of 74 and a varying baseline in the patients.

The exclusion of those aged over 74 is a downfall, due to the fact that the majority of

Clostridium difficile infections are older adults. However, this weakness alone does not discredit

the results of the trial.

Youngster et al. (2014) conducted an open label randomized control trial to determine the

differences in effectiveness, safety, and side effects of Fecal Microbiota Transplants via

colonoscopy and Nasogastric administration. The participants were 20 people varying from 7-90
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years old with recurrent Clostridium Difficile as defined by diarrhea and a positive toxin stool

test. The control group (n=10) received FMT via colonoscopy and the intervention group (n=10)

received FMT via nasogastric tube. Results showed that the colonoscopy group received slightly

better results than the NGT group, however the findings were not statistically significant

(P=0.481). Strengths of the study include a randomized design, follow up assessments were

preformed out to 6 months, and instruments used were valid and reliable. The two weaknesses of

the study are the small sample size and that participants and providers were not blind to the study

group. This weakness is easily explained due to the inherent and obvious differences in

treatment.

Surawicz et al. (2013) developed guidelines for the treatment of Clostridium Difficile. This

guideline lays out a protocol for the treatment and management of Clostridium Difficile, taking

into consideration the severity of the infection and the number of recurrences. It also strategies

for the prevention of Clostridium Difficile and methods to prevent its spread. In cases of three or

more recurrences, they recommend the consideration of Fecal Microbiota Transplantation as a

treatment.

Synthesis

The trial conducted by Cammarota et al. (2015) showed a significantly higher rate of Clostridium

Difficile remission in those patients treated with fecal transplantation than the group treated with

vancomycin (P<.0001). Interestingly, Youngster el al. (2014) determined that the colonoscopy

route was not significantly more effective than delivery via a nasogastric tube.

In addition, the clinical trial by Kelly et al. (2016) showed that those treated with donor stool

were more likely to be clinically cured than those treated with autologous stool (P=0.042). This

study also highlights the safety of properly preformed fecal microbiota transplantation.
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Gastrointestinal guidelines support the use of fecal microbiota transplantation in cases of

recurrent Clostridium difficile.

Research has shown that FMT procedures are more effective in treating recurrent

Clostridium difficile than traditional antibiotic therapy (Surawicz et al., 2013). The effectiveness

of FMT via Nasogastric administration and colonoscopy was not statistically significantly. This

highlights the importance of evaluating the risks associated with each for of administration,

namely anesthetic risks for the colonoscopy route and aspiration risks for the nasogastric route

(Youngster, 2014).

Clinical Recommendations

Recent research has shown that Fecal Microbiota Transplantation is a safe and extremely

effective treatment for Recurrent Clostridium Difficile Infections (Surawicz, 2013). More

research is needed to determine the superior method of administration, as there are risks

associated with each route of administration (Youngster, 2014). Fecal Microbiota

Transplantation may be a safer and more effective alternative to antibiotics in the treatment of

Recurrent Clostridium Difficile.

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References

Cammarota, G., Masucci, L., Ianiro, G., Bibb, S., Dinoi, G., Costamagna, G., ... &

Gasbarrini, A. (2015). Randomized clinical trial: faecal microbiota transplantation by

colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile

infection. Alimentary pharmacology & therapeutics, 41(9), 835-843.

Kelly, C. R., Khoruts, A., Staley, C., Sadowsky, M. J., Abd, M., Alani, M., ... & Reinert,

S. E. (2016). Effect of Fecal Microbiota Transplantation on Recurrence in Multiply

Recurrent Clostridium difficile Infection A Randomized Trial Fecal Microbiota

Transplantation and Recurrent C difficile Infection. Annals of Internal Medicine, 165(9),

609-616.

Lessa, F. C., Mu, Y., Bamberg, W. M., Beldavs, Z. G., Dumyati, G. K., Dunn, J.
R., ... & Wilson, L. E. (2015). Burden of Clostridium difficile infection in the United
States. New England Journal of Medicine, 372(9), 825-834.
Surawicz, C. M., Brandt, L. J., Binion, D. G., Ananthakrishnan, A. N., Curry, S. R., Gilligan, P.
H., ... & Zuckerbraun, B. S. (2013). Guidelines for diagnosis, treatment, and prevention
of Clostridium difficile infections. The American journal of gastroenterology, 108(4),
478-498.
Youngster, I., Sauk, J., Pindar, C., Wilson, R. G., Kaplan, J. L., Smith, M. B., ...

& Hohmann, E. L. (2014). Fecal microbiota transplant for relapsing Clostridium difficile

infection using a frozen inoculum from unrelated donors: a randomized, open-label,

controlled pilot study. Clinical Infectious Diseases, 58(11), 1515-1522.