Integrative Review of Literature

Michael A. Gray

Bon Secours Memorial College of Nursing

NUR 4322

Dr. Christine Turner

11/13/2020

“I Pledge…”
 Abstract

Purpose: The purpose for this paper is to examine five peer-reviewed research articles that are

examining the relationship between different pharmacological therapies versus fecal stool

transplantation in the treatment of C. diff and to see which is more effective. Background: C. diff

infections are on the rise within the United States and worldwide. The need for a comprehensive and

effective treatment option that is safe and prevents relapses of this bacterium can save many lives and

money. Design and Search Method: The research design for this paper is one of an integrative review.

Open Athens available by the College of Nursing allowed me access to The New England Journal of

Medicine of which all five of my original articles came from. Results and Findings: The evidence

compiled in this integrative review came with arguments on both sides; however, the strongest

argument was for the fecal stool transplantation. The difference in drug combinations gave the

strongest argument for pharmacological interventions even though vancomycin was at the center of one

study. Limitations: The researcher is not well equipped to compile a thorough integrative review and

lacks experience and knowledge upon this style of review. Implications for practice: If fecal

transplantation is shown to have fewer side effects and safety considerations over pharmacological

interventions then this can open treatment options for others. Recommendations: Future research

should expand on cost effectiveness of one treatment versus another as well as expand qualitative

studies to see if there were any psychological implications of choosing one option or another.

Integrative Review of the Literature

The purpose of the integrative review is to compare whether pharmacological options are best

or whether fecal transplantation is better for the treatment of C. diff. Currently C. diff infections counts

for 12.1% of health-care acquired infections within the United States (Magill et al., 2014). Medications
such as vancomycin have been in existence for many years as a front line therapy but breakthroughs in

technology have allowed us to search for fecal donors who can safely replace the intestinal flora safely

with fewer side effects that can be present within pharmacological options. However, we have seen that

people have opted for pharmacological options since the idea of a donor’s fecal matter is culturally

revolting (Lowy et al., 2010). Doctors are also very hesitant to change treatment options without

increased levels of data which pharmaceutical companies have had for years. The researcher brought in

an article that discusses different genomes related to C. diff and how that can affect treatment options

(Eyre et all., 2013.) The articles had to relate in a relevant way the researcher’s original PICOT question,

In patients with  C. diff  infections what is the effect of fecal stool transplants on recovery rates versus

standard pharmacological therapies (such as metronidazole, vancomycin, and fidaxomicin) within five

years?

Designs and Methods

This research design utilized within this paper is an integrative review. The New England Journal

of Medicine was the primary search engine source used for this research through access to Open Athens

through access of the College of Nursing. Computer based engines such as PubMed were utilized but did

not produce articles relevant to the PICOT question. Search terms that were used were “C. diff´,

“treatment options”, “pharmacological”, and “fecal transplantation.” Inclusionary principles for articles

had to be within the past 10 years, focus on treatment of C. diff, and any pharmacological treatments

outside of the current use of vancomycin and fidaxomicin. The researcher wanted to also include within

the review an overall look of the health-care system within the United States in terms of hospital

acquired infections since the source of many C.diff infections occur within the hospital. The search

engine produced about 60 articles of various article types. Although there were quality articles that

were uncovered the researcher noted that there was a lack of articles with substantial research articles
as well as a minimal number of articles that do not reflect the current problems of C. diff infections

within health care systems around the world. The search engine was refined to only include original

articles which led to the five studies being presented and reviewed within this paper. Dates for these

articles range from 2010-2019. These articles had to be published in English, written by those

knowledgeable about the subject, and peer reviewed articles.

Findings and Results

In many of the articles that were researched there was a mixture of outcomes. The first

outcome said that fecal transplantation was successful, but studies needed to be done to make sure that

other bacteria such as E. Coli would not become rampant and cause other issues. With pharmacological

interventions there was less evidence that they were as effective as fecal transplantation just with one

drug. However, polypharmacological interventions had a high success rate to par with fecal

transplantation but are the side effects to newer generations drugs, such as monoclonal antibodies,

outweigh the benefits of such therapies. Major themes that emerged were the severity and rate of C.

diff infections within health care systems as well as the increased diversity of treatment options for

these infections since C. diff can evolve to resist treatment options especially antibiotics.

The severity of C. diff infections within healthcare systems and implications

Two articles that were included within the literature review discussed two issues that surround

the need for increased studies surrounding C. diff infections. The first article addressed the genomics of

C. diff through multilocus sequence typing and investigating if different genetic variations within this

bacterial accounted for transmission of the bacteria either through hospitalization or from other

sources. The findings resulted that 38% of patients acquired through close contact of an infected patient

and 36% had no hospital contact with genomic sequencing that are consistent with contact
transmission. The researchers of this study found that 45% of infectious cases came from variations of

the bacteria that were not consistent from previous contact cases which means that other modes of

transmissions other than hospital acquired were involved (Eyre et al., 2013).

The other article highlighting the severity of hospital acquired infections focused on the need of

a need for a single surveillance system of hospital acquired infections within American healthcare

systems. Data was collected within 183 hospitals within 10 state health departments involving 11,282

patients within a single day survey. Out of the 183 hospitals, 93 (51%) were considered small hospitals,

68 (37%) were considered medium capacity, and 22 (12%) were considered large capacity. 452 patients

were found to have one or more hospital acquired infection with C. diff identified as the most common

infection (12.1%). The authors of the study found that while UTI and pneumonia infections were the

main focus of prevention programs within health care systems they only accounted for 25.6% of total

infections. Likewise, infections stemming from S. aureus which is a focus currently within health-care

systems only accounted for 10.7% of acquired infections. Admitted patients were included within this

study and outpatient, ED, psychiatry, skilled nursing, and rehabilitation patients excluded from the

study. 71.2% of patients were identified within non-nursery wards and 15.1% were identified within

critical care units. 169 of 394 non-surgical site infections (42.9%) developed within 48 hours after

admission within a critical care unit. 167 (42.4%) of infections developed within 48 hours after admission

within a non-nursery ward (Magill et al., 2014).

Diversity of treatment options needed for increased C. diff infections

Each of the five articles discussed the need for various treatment options for initial and

recurrent C diff. infections. Two articles highlighted the use of monoclonal antibodies as a new

pharmacological treatment option. Both articles were double-blind, placebo-controlled studies that

reflect normal pharmacology research studies. Both articles had significant sampling size with one
involving 2655 adults in phase three trials, named MODIFY I and MODIFY II, receiving two monoclonal

antibodies (Wilcox et al., 2017) and the other involving 200 patients receiving two unnamed monoclonal

antibodies targeting two different toxins produced by C. diff (Lowy et al., 2010). The other article

discussing treatment options was the study done on duodenal infusion of donor feces through a fecal

stool transplantation. This article randomly assigned patients to receive one of three therapies from a

sampling size of 16 patients. One group would receive vancomycin only, vancomycin combined with a

bowel lavage, and vancomycin combined with a bowel lavage as well as an infusion of donor feces. The

design of the study was to differentiate pharmacological treatments versus combination therapies (van

Nood et al., 2013).

The findings of the use of two monoclonal antibodies, identified as actoxumab and

bezlotoxumab, was that the inclusion of bezlotoxumab plus a standard of care antibiotic reduced the

number of recurrent infections by 77% within the MODIFY I trial and 83% in MODIFY II trial. Likewise,

Bezlotoxumab plus an antibiotic showed a drop of 10 percentage points of recurrent infection versus

standard treatment. No significant difference was shown when actoxumab was added which the

researchers noted that toxin B, of which bezlotoumab is designed to be effective against, is the

prevalent C. diff infection within humans (Wilcox et al., 2017). Within the study that focused on single

infusion of monoclonal antibodies targeting toxin A and toxin B found that only 7% of the 101 patients

given the antibodies had a recurrent infection versus 25% within the placebo group. The researchers

found only two serious events from the infusion of the monoclonal antibodies versus 34 adverse effects

within the placebo group (Lowy et al., 2010). Within the article studying duodenal infusion procedures

versus pharmacological therapies 13 out of 16 patients (81%) within the combined vancomycin/bowel

lavage/infusion group had no recurrent infections. The remaining three patients received a second

infusion and found 2 patients had resolution of diarrhea. Within the vancomycin along group only 4 out
of 13 patients (31%) had resolution of diarrhea and only 3 out of 13 patients had resolution within the

vancomycin plus bowel lavage group (van Nood et al., 2013).

Discussion and Implications

The articles within this integrative review offer a look into the future of treatment of

preventable hospital acquired infections such as C. diff and show that there is an increasing number of

options that a patient could select. Some clarification was obtained by the PICOT question, In patients

with  C. diff  infections what is the effect of fecal stool transplants on recovery rates versus standard

pharmacological therapies (such as metronidazole, vancomycin, and fidaxomicin) within five years? Each

article supported that new treatments other than the standard vancomycin taper are more effective.

Implications for this should be shown to insurance companies so that there is more coverage for these

advanced therapies versus having insurance companies cover the cost of increased and frequent

hospitalizations. An increased number of treatments as well as the awareness of C. diff infections can

hopefully bring about a new awareness of this possible deadly infection as well as reduce costs of

healthcare within our country. Other implications that can be deduced from this literature review are

that these specific treatments can be implemented earlier within hospitalization which can reduce

overall hospitalization which can decrease health care costs.

Limitations

In organizing this integrative review, the review had some limitations. The researcher has

limited information about how to do the most effective integrative review since training for it was

offered online and has limited resources attached to it. An inherent limitation within this integrative

review is the limitation of only five articles due to the nature of the course being an introduction to
nursing review. Another limitation within this literature review is that the research and development of

new treatments for C. diff infections are a current phenomenon and it will take more time to bring about

new therapies and/or procedures.

Upon review, the researcher noticed that four of the five chosen articles were studies where

one article was more of a question-based research study versus a randomized clinical trial. As that

difference might have been deemed significant the particular article was used in this review as

information to be used to be a foundation for the PICOT question. Within genomic sequencing of C. diff,

the researchers stated that there more sensitive and two step genomic testing existed and that

asymptomatic adults as well as children were not tested, therefore, a wider scope of potential sources

of transmission were not included (Eyre et al., 2013). In the study of multistate survey of hospital

acquired infections the limitations that were identified were that only 10 states were surveyed and did

not represent the entirety of the nation which could skew the results. Likewise, the survey was only

done within a single day therefore trends could not be studied to see if rates were increased or

decreased (Magill et al., 2014). In the study of duodenal infusion versus solo or combination therapies

limitations that were identified were that the patients involved had multiple relapses of infection so it is

unknown if this procedure would be effective against initial infections (van Nood et al., 2013). Within

the study done with bezlotoxumab and actoxumab limitations that were identified was that the

standard of care antibiotic was not standardized which would see if any one standard antibiotic would

be more effective with the dual monoclonal antibodies. Likewise, no other therapy was used within this

study so there is no evidence if the monoclonal antibody plus transplantation would be more effective

(Wilcox et al., 2017). Within the study focusing on the monoclonal antibodies focusing on specifically

toxin A and toxin B the patients that were studied were significantly older and had a significant higher

severity of infection than outpatients. Likewise, some patients showed lower serum levels of the
antibodies and the researchers did not increase levels of the antibodies to see if truly these two

antibodies were truly effective (Lowy et al., 2010).

Conclusion

The researchers from these five articles highlight that all treatment options do have some level

of risks as well as some patients may not respond to what most patients would benefit from the most.

The major findings of all five articles showed that advanced treatment options are most effective against

recurrent infections of C. diff as well as a need for increased awareness of this disease. This literature

review shows that fecal stool transplantation is very effective but that newer pharmacological agents

could be as effective as a transplantation. Further research within both types of therapies need to be

implemented so that the PICOT question could be more effectively answered.

References

Eyre, D. W., Cule, M. L., Wilson, D. J., Griffits, D., Vaughn, A., O’Connor, L., Ip, C. L. C., Golubchik, T.,

Batty, E. M., Finney, J. M., Wyllie, D. H., Didelot, X., Piazza, P., Bowden, R., Dingle, K. E., Harding,

R. M., Crook, D. W., Wilcox, M. H., Peto, T. E. A., Walker, A. S. (2013). Diverse sources of C.

difficile infection identified on whole-genome sequencing. The New England Journal of

Medicine. 369(13).

Lowy, I., Molrine, D. C., Leav, B. A., Blair, B. M., Baxter, R., Gerding, D. N., Nichol, G., Thomas, W. D.,

Leney, M., Sloan, S., Hay, C. A., Ambrosino, D. M. (2010). Treatment with monoclonal antibodies

against Clostridium difficile toxins. The New England Journal of Medicine. 362(3).

Magill, S. S., Edwards, J. R., Bamberg, W., Beldavs, Z. G., Dumyati, G., Kainer, M. A., Lynfield, R., Maloney,

M., McAllister-Hollod, L., Nadle, J., Ray, S.M., Thompson, D. L., Wilson, L. E., Fridkin, S. K. (2014).
 Multistate point prevalence survey of health care-associated infections. The New England

Journal of Medicine. 370(13).

Wilcox, M.H., Gerdling, D.N., Poxton, I.R., Kelly, C., Nathan, R., Birch, T., Cornely, O.A., Rahav, G. Bouza,

E., Lee, C., Jenkin, G., Jensen, W., Kim, Y.-S, Yoshida, J., Gabryelski, L., Pedley, A., Eves, K.,

Tipping, R., Guris, D., & Kartsonis, N. (2017). Bezlotoxumab for prevention of recurrent

Clostridium difficile infection. The New England Journal of Medicine. 376(4).

Van Nood, E., Vrieze, A., Nieuwdorp, M., Fuentes, S., Zoetendal, E. G., de Vos, W. M., Visser, C. E.,

Kuijper, E. J., Bartelsman, J. F. W. M., Tijssen, J. G. P., Speelman, P., Dijkgraaf, M. G. W., Keller, J.

J. (2013). Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England

Journal of Medicine. 368(5).

APA Citation Author Israel Lowry, M.D., Ph.D-Medarex, Princeton, NJ

Qualifications Deborah C. Molrine, M.D., M.P.H- University of
Massachusetts Medical School, Boston.
Background/Problem New more targeted therapies are needed for the treatment of
Statement C. diff such as monoclonal antibodies that could neutralize C.
difficile toxins A (CDA1) and B (CDB1)

Conceptual/theoretical Framework was organized around an experimental study

Framework aiming to look at finding out if a particular theory was correct
or not. It was also a quantitative study to see how much data
could be found out.
Design/ The methodology was a randomized, double-blind, placebo-
Method/Philosophical controlled study of two monoclonal antibodies targeted at two
Underpinnings specific toxins related to the C. diff infection. A philosophical
underpinning that could be brought to light is that there in an
increase of interest in monoclonal antibodies that can target
diseases without interrupting other body processes.
Sample/ Patients were enrolled at 30 sites across America and
Setting/Ethical Canada. Ethical considerations would have to come into play
Considerations because Canadian health care policies could vary different
 from American policies and could be dictated by province.
Likewise, sharing information over the internet could be a
target for hackers who could sell information to third body
parties to influence factors such as stock prices.
Major Variables To see if the monoclonal antibodies were truly affective
Studied (and their versus a placebo.
definition), if
appropriate

Measurement Measurement was laboratory-documented recurrence of

Tool/Data Collection infection during 80 days after the administration of the
Method antibiotics or the placebo.

Data Analysis Statistical analysis was performed with JMP software and
StatXact. Nominal variables were compared with a two-sided
Fisher’s test and continuous variables were compared with a
two-sided t-test. P value of less than 0.05 was considered
significant.

Findings/Discussion Although the monoclonal antibodies were not that effective

themselves against the infection when placed with another
typical antibiotic used to treat C. diff such as vancomycin it
increased the success rate of the antibiotic versus just the
antibiotic itself. The discussion behind this is that we can take
these monoclonal antibodies with combination of a typical
antibiotic and hopefully decrease relapse hospitalizations
especially in elderly populations.

Appraisal/Worth to The authors of the study agree that a larger study needed to
practice be performed furthermore, however, this makes a case for
insurance companies to start expending new pharmaceutical
therapeutics versus traditional hospitalization.

APA Citation Author Shelly S. Magill, M.D., Ph.D- Centers for Disease and Control
Qualifications and Prevention
Jonathan R. Edwards, M.Stat- Centers for Disease and
Control and Prevention
Laura McAllister-Hollod, M.P.H.-Centers for Disease and
Control and Prevention
Scott K. Fridkin, M.D.-Centers for Disease and Control
Et. al.
Background/Problem There is no major one healthcare surveillance center that can
Statement estimate health care burdens in terms of sickness and cost to
local communities.

Conceptual/theoretical The theoretical framework is exploratory research so that a

Framework question can be formulated so that another study may be
formed to further a need.
Sample/ The idea that we need a national health care surveillance
Setting/Ethical system that can funnel and organize health care information
Considerations is nothing new within the medical community but many
outside of the medical community are weary of such as they
feel it is a breach of privacy rights.
Major Variables The amount of hospital acquired infections that can be
Studied (and their prevented or not through improved sanitization techniques.
definition), if
appropriate

Measurement Surveys were developed in two methods: a single pilot survey

Tool/Data Collection and then a limited roll out survey across 10 state health
Method departments across the country which was asked to chose
between small sized, medium sized, and large sized hospitals
to encompass a wide demographic.
Data Analysis Data was analyzed with use of SAS software and OpenEpi
software. Log binomial regression was used to identify factors
associated with prevalence with HAI.

Findings/Discussion Out of all the commonly reported pathogens C. diff was the
number one reported pathogen (12.1% of HAI within the
United States). The highest common type of infection within
the United States was Pneumonia with 21.8% of all
infections. The discussion that revolves around this is that
health care systems need to start having tighter sanitization
techniques and that many of these diseases can be
preventable if proper PPE and hand hygiene were followed
by healthcare staff as well as patients.

Appraisal/Worth to This study shows how horribly prevalent HAI are within our
practice healthcare system when the public opinion is that we have a
very clean and safe healthcare system.

APA Citation Author Els van Nood-M.D. from Department of Internal Medicine
Qualifications Anne Vrieze-M.D. from the Department of Medicine
 Caroline E. Visser-M.D. from Gastroenterology
Erwin G. Zoetendal-Ph.D from Laboratory of Microbiology at
Leiden University Medical Center, Leiden
Josbert J. Keller, M.D, Ph.D- Department of
Gastroenterology, Hagaziekenhuis, The Hague
Background/Problem Whether Duodenal Fecal Infusion of Donor Feces had better
Statement success rates than pharmacological routes which can have
high failure rate.

Conceptual/theoretical The conceptual framework that was presented within this

Framework article was of working hypothesis in which the researcher is
trying to prove if duodenal fecal infusion is necessary
superior to the typical antibiotic route.
Design/ Random assignment of patients to receive one of three
Method/Philosophical therapies: a vancomycin taper (500 mg orally four time a day
Underpinnings for four days) which was followed by a bowel lavage and
infusion of a solution of donor feces through a ND tube; a
standard vancomycin regimen with a bowel levage; or a
standard vancomycin regimen.
Sample/ A sample of 42 patients with an infection of C. diff and had to
Setting/Ethical be at least 18 years old of age, have a life expectancy of at
Considerations least 3 months and have had a relapse of C. diff after a
adequate antibiotic therapy. Exclusions were made to those
who were on chemotherapy or otherwise
immunocompromised.
Major Variables Major variables that were studied were the types of
Studied (and their treatments and how effective they were in any reoccurrence
definition), if in C. diff.
appropriate

Measurement The measurement tool was that after 10 weeks after

Tool/Data Collection receiving a treatment without any reoccurrence of infection
Method then that treatment would be deemed effective. Patients were
asked to keep a diary and were questioned about any
adverse effects or frequency and consistency of stools on
days 7, 14, 21, 35, 70.

Data Analysis Analyses were performed on modified intention-to-treat basis

and differences in cure rate were assessed with Fisher’s
exact probability test. Simpson’s Reciprocal Index of diversity
any statistical significance of change was assessed with use
of paired sampled of a Student t-test.

Findings/Discussion Of 16 patients who were in the infusion group about 13 (81%)

had resolution of symptoms. In the group
APA Citation Author Daniel J. Wilson, D.Phil from the Nuffield Department of
Qualifications Clinical Medicine
Derrick W. Crook- M.B., B.CH from the Nuffield Department
of Clinical Medicine
Tim E. A. Peto- D.Phil from Oxford University Hospitals
National Health Service Trust
A. Sarah Walker-Ph.D from Medical Research Council,
Clinical Trials Unit, London
Et. al.
Background/Problem The problem and background were identified that it has been
Statement thought that the spread of C. diff has been a hospital only
problem but with the occurrence of C. diff cases outside of
the hospital setting the researchers wanted to figure out if
there were more evolutions of the virus than previously
recorded.

Conceptual/theoretical The framework that these researchers are going to use is an

Framework exploratory style. They want to figure out, through numbers,
where people are acquiring new infections whether it is in the
hospitals or out within the community.
Design/ All patients that had 3 or more incidences of diarrhea
Method/Philosophical automatically underwent test for C. diff. The immunoassays
Underpinnings for toxins A and B were analyzed. Sets were separated
whether it was possible hospital acquired or community
acquired. Then whole genetic sequencing as well as
determining the single-nucleotide variants were undertaken.
The reason why the SNV were considered was because it
would seem to give a specific new mutation if one had
occurred.
Sample/ An ethical question that could be brought up would be if they
Setting/Ethical patient had the option of refusing the test. The settings were
Considerations 90% in hospitals within Oxforshire, UK. 40,924 fecal samples
were collected.
Major Variables Major variables studied were if the stool sample had the C.
Studied (and their diff bacteria within it, where the patient may or may not have
definition), if acquired it (through the hospital, brought in through the
appropriate hospital, or acquired with close contact with a patient with the
infection).
Measurement Data collection was through samples obtained by patients
Tool/Data Collection why had come into the hospital with 3 or more cases of loose
Method diarrhea per day. Samples were sent down to the lab where
the DNA was sequences and extracted using Illumina
technology. Then the sequences were read to a reference
genome of C. diff to see if there were any mutations within
the specimen collected and the reference genome.
Data Analysis 333 cases or about 35% were genetically related to another
isolate in which genetic relationship was defined as having a
different of at or less than 2 SNV. Of 957 samples sequences
there were 428 (45%) that had more than 10 SNV. In 333
patients with the infection 38% were to have been infected
within the ward where only 5 (2%) were related to caring for a
patient that had an infection.

Findings/Discussion Out of 40, 924 fecal samples about 2,377 were positive for
the enzyme immunoassay. Out of that positive immunoassay
group about 2,283 were tested for C. diff and out of those
cultures 1714 were positive for C.diff. Out of these 1714
positive samples 862 (71%) came from the inpatients at
Oxford University Hospitals, 246 (20%) came from general
medical practices, 60 (5%) came from Oxford University
outpatient centers and 55 (4%) came from other hospitals

Appraisal/Worth to Knowing where the majority of C.diff infections come from

practice can help reduce infection rates as well as possible secondary
and tertiary rates. If we know that the main issue is within
health care setting including PCP and outpatient centers then
we can tighten up or reformulate sanitization protocols that
happen within those centers. If doctors and nurses are
lightning up on hygiene practices within these non-traditional
hospital settings then reeducation is vitally important.
APA Citation Author Mark H. Wilcock. M.D-University of Leeds
Qualifications Dale N. Gending, M.D. University of Leeds
Ian R. Poxton, M.D- University of Edinburgh
Ciaran Kelly, MD.-University of Edinburgh
Et. al.
Background/Problem C. difficile is one of the most common cause of HAI within
Statement hospitals. The author looks at the efficacy of two monoclonal
antibodies, such as Actoxumab and bezlotoxumab, to see if
there is a decrease of recurrent C. diff infections within the
hospitalized patient.

Conceptual/theoretical The framework was qualitative using theory to support the

Framework original problem.
Design/ Design was a double-blind, randomized, placebo, phase 3
Method/Philosophical trail involving 2665 adults receiving standard antibiotics for
Underpinnings either primary or recurrent C. diff infections. Those only
receiving a bezlotoxuman only receive 10mg/kg), those
receiving the Actoxumab and the bezlotoxumab received
10mg/kg each, and those receiving just the Actoxumab only
received 10 mg.
Sample/ Sample size was quite high of 2,655 adults throughout 322
Setting/Ethical sites in 30 countries/ An ethical consideration that would
Considerations come up with this study would be were medical conditions
and procedures communicated well within each country. The
setting was performed within the Leeds Teaching Hospitals,
in the UK.
Major Variables Major variables that were studied were: would these two
Studied (and their medications, either alone or concurrent, would be able to see
definition), if a decrease in reoccurring C diff infection.
appropriate

Measurement Data collection was through data recorded by participants

Tool/Data Collection about the state of their stools for up to 90 days. If new
Method reoccurrences after the initial treatment happened
participants would be monitored by telephone during another
round of preinfusion as well as seeing if there were any
reactions that the researchers missed.

Data Analysis Both data from both groups were pooled in an integrated
statistical analysis plan per protocol but also showed data
from subgroups within the study that may have been missed.

Findings/Discussion In the trial out of the 2,655 about 85% completed the whole
week trial. Greatest indicator for not following up was death.
The final results was that the two drug group had greatest
 success where in the just actoxumab group there were
slightly higher reoccurrences of C. diff where in the only
bexlotoxumab there were higher significant of death. This
discusses whether there will ever be one pill that can cure a
disease or we would need a multitude of pharmacological
routes.

Appraisal/Worth to The appraisal for this study is that it is trying to find out other
practice ways that C. diff could be eradicated since this disease is
quite opportunistic. If we can use the dual drug combo and if
it is cheaper than the current fidaxomicin/vancomycin taper
than that is one less antibiotic that can be mutated against.