Clostridial Infection and Oral Lavage -Improving Treatment Before Illness Becomes Severe
Clostridial Infection and Oral Lavage -Improving Treatment Before Illness Becomes Severe
Once the lab test is positive for c. diff, the investigators will order the patient to have
 PEG 3350 solution, one 8oz glass every ten minutes until 6 liters are gone, but if still not
 clear 2 more liters may be ordered. At enrollment, the treatment arm will have an order for
 500 cc Normal saline to be given I.V. The patient will continue with antibiotic treatment as
 well. The investigators will plan to check c. diff tests daily to see when they become
 negative. The investigators will perform chart audit/review to track mortality, the length of
 stay, ICU days, surgical intervention, and APACHE scores (assessment of disease severity).
 Chart audit will be used to collect data on their diet and how they feel using a visual
 analog scale (collected by nursing staff daily as a standard procedure; see attached pain
 scale). Using chart audit, the investigators will record whether the patient is
 immunocompromised or not.
Project Summary:

 Clostridium Difficile (c. diff) is a bacteria which causes much morbidity and mortality
 worldwide. It does so by causing diarrhea and abdominal pain. It can be mild and
 self-limited, to severe and lethal, even in developed countries. It can require removal of
 the colon to try to spare a victim's life. This isn't always successful. Current treatment is
 withdrawal of any unnecessary antibiotics, addition of one of two antibiotics that work
 pretty reliably against c.diff, hydration, and observation for signs the patient might need
 to be operated.

 The investigators propose that instead of trying to kill the bacteria that are a problem,
 with limited antibiotic choices, the investigators can give the patient a bowel prep and
 quickly and reliably wash the bacteria, and the toxin that actually wreaks the havoc, out of
 their system.

 The investigators will collect variables of mortality, LOS, ICU days, surgical interventions
 (colectomy or ileostomy and lavage), time to test negative after treatment starts, and APACHE
 scores. The investigators will track when regular diet is resumed. The investigators will
 track immunocompromised state and see the effect it has. The investigators will use a visual
 analog scale to assess time to feel better as well.

 Project description:

 Rationale- Clostridium difficile (c. diff) is a bacteria in the gut which has the ability to
 make us very sick by releasing toxins which cause colitis. It has traditionally affected the
 hospitalized and those who have recently had antibiotics. Recently the investigators have
 seen more community acquired cases as well as cases with no antibiotics preceding the
 infection. C. diff can produce self-limited diarrhea and bloating, or become very severe and
 include severe diarrhea, bowel necrosis, toxemia and death. Over the last four years at
 Genesys, death rates with c. diff (all cause mortality rates) have averaged 9.6% of those
 infected. The investigators have averaged over 230 cases per year of c. diff infections.
 Clearly this is a big problem.

 Traditional treatment is IV fluids, one of two antibiotics (vancomycin or flagyl) along with
 bowel rest, and withdrawing any unnecessary broad spectrum antibiotics (Cohen, 2010.) This
 helps most people, but can still progress in some cases. If the disease is or becomes severe
 enough, near total colon resection is required (surgery), but by that point in the disease
 process, 35-80% will die anyway (Neal, 2011.) Those that survive have a lot of morbidity from
 the ileostomy they now have (the hassle of stooling into a bag, and the dehydration that
 frequently accompanies the ileostomy). It's an extremely challenging problem which should be
 feared to worsen if and when it becomes resistant to the very few antibiotics that are
 currently effective. The investigators need to find a better way to treat it.

 Recently out of Pittsburgh, a study was performed in which they took very sick patients to
 the operating room earlier and diverted the stool stream with an ileostomy and flushed
 Go-Lytely (polyethylene glycol) through the colon to clean it out of all the stool, bacteria,
 and toxin (but did not remove the colon), followed by antibiotics through the colon. They
 showed a reduction in the mortality rate after surgery from 50% down to 19% for a reduction
 of 62% (Neal, 2011). The results are very promising, but this process does require two
 operations - one to make the ileostomy and another to reverse the ileostomy later on. It also
 waits until the patients get very sick to clean out the GI tract of the bacteria and toxin.

 A second paper reported two cases of chronic c. diff patients taking a bowel prep of
 Go-Lytely by mouth, and then being 'cured' after 36-48 months and counting (Liacouras, 1996).

 In the investigators study, the investigators will still withdraw any unnecessary
 antibiotics, provide hydration, and treat with the same antibiotic regimen the admitting
 physician has decided on. But the investigators will also add a bowel prep of polyethylene
 glycol 3350 solution (PEG solution), to flush out the stool and bacteria. The investigators
 suspicion is that by giving c. diff patients a bowel prep of PEG solution orally (or
 nasogastric tube if unable to swallow), the investigators can wash out the c. diff bacteria
 and toxin they have already produced, instead of trying to kill the bacteria still in the
 colon. The investigators think the investigators can effectively treat even sick c. diff
 patients without an operation. In fact, the investigators can quite possibly prevent many
 mild cases from progressing to severe cases in the first place, thereby greatly decreasing
 the morbidity and mortality of this scary disease.

 Objective- The investigators primary objective is to show that oral administration of
 polyethylene glycol bowel prep solution decreases mortality in clostridium difficile infected
 patients. Secondary objectives include showing decreased length of hospital stay, decreased
 ICU days, decreased time to test negative for c. diff toxin in the stool, and decreased
 surgical interventions, and better patient perceptions. The investigators will use a visual
 analog scale to track how quickly patients perceive they are better. The investigators will
 also determine if timing of diet resumption or immunocompromised status changes outcomes in
 the study.

 Methodology- The study will be a prospective, randomized, controlled trial. Eligible patients
 will be assigned by a computer generated, randomized list to either standard treatment (IV
 fluids and vancomycin or flagyl) or the intervention treatment (IV fluids, vancomycin or
 flagyl, and oral bowel prep).

 Study subject criteria includes: all adults greater than age 18, testing positive for c. diff
 as GRMC inpatients. Testing will be via either DNA amplification assay, or through flexible
 endoscopic diagnosis. The lab or endoscopist will contact Dr. Vance or Dr. Alvarez, and they
 will approach the patient to then consent, enroll, and randomize them.

 There are no sex or ethnic background exclusion criteria, and health status of the patient
 will not alter patient selection. The investigators plan to enroll a total of 400 subjects.

 Exclusion criteria include:

 1. Pregnancy

 2. Less than 18 yrs of age

 3. Mentally handicapped

 4. Those sick enough to require surgery at diagnosis shall not be enrolled, as they should
 be operated at that point.

 5. Patients in whom severe ileus or suspected small bowel obstruction is present.

 Interventions- Nu-Lytely or Go-Lytely (polyethylene glycol 3350), produced by Braintree
 Laboratories, Incorporated, will be administered to the study patients. These two products
 are interchangeable at the investigators institution and work by the same mechanism of action
 as a mechanical bowel prep. They will be dosed at one 8oz glass, orally, every 10 minutes
 until 6 liters are ingested. If they are not having clear bowel movements at that point, then
 2 more liters will be given. If there is difficulty drinking the solution, the investigators
 will offer to place a nasogastric tube to deliver the PEG solution to the GI tract. It is FDA
 approved for bowel cleansing, though not specifically for clearing c.diff. It has a long
 history of effective bowel prepping with good patient safety.

 Because the PEG solution can be dehydrating to a degree, the investigators will plan to give
 a 500 mL IV bolus of saline with the start of the bowel prep to prevent this from being an
 issue. These patients are generally dehydrated from the disease process anyway, and IV fluids
 are generally a good idea. The investigators will monitor the patients' BUN and creatinine,
 blood pressure, heart rate, and urine output and treat additionally for dehydration as
 needed.

 If a patient's electrolytes are significantly abnormal at enrollment, the investigators may
 order an additional chemistry panel that evening to ensure this is not worsening. The
 investigators expect this would already be ordered by the primary physician in most cases,
 even without the PEG solution, in routine patient care.

 To accomplish the investigators secondary objective of time to test negative for c. diff, the
 investigators will also collect stool to test for c. diff daily, starting the day after
 enrollment until negative. This will be the Immuno card c. diff toxins A& B test (available
 from Meridian Bioscience), as the DNA amplification method can yield false positive results
 with bowel preps.

 Observations- The observations made by chart review after discharge will include mortality,
 length of stay, operative interventions, and presenting APACHE scores. Time to test negative
 after treatment starts will be assessed daily, and be based on stool testing results. Diet
 will be at the admitting physicians' discretion based on the patient status, but the
 investigators will monitor to see if it seems to affect successes in treating the c. diff.
 Additionally, the investigators will use a visual analog scale to determine when patients
 feel better. Nurses are required by standing policy to record visual analog pain scale
 responses (scale is attached). The investigators will use these responses for the study.

 Sample size- To show that a mortality reduction of 70% is significant in a population with
 10% mortality, a power analysis determined that 200 in each group is required to achieve 82%
 power detection. A total of 400 subjects will be enrolled into the study.

 Data Management and Analysis- The primary hypothesis of comparing mortality between groups
 will be conducted using Chi square analysis. The secondary hypothesis of comparing mean days
 to negative test for c. diff toxin, will be analyzed using the Independent Students' t-Test
 for means (Mann Whitney-U test for comparing median number of days). Hospital and ICU LOS
 will be compared using Students' t-Test and patient perceived improvement will be compared
 using the Mann Whitney-U test. Surgical intervention rate will be compared by group with
 Chi-square analysis.

 Ethical Considerations:

 The study is ethical based on the possibility of a more effective way to treat a difficult
 disease, and the possibility of decreasing the patients' own mortality and rate of surgical
 interventions. The possible nausea, dehydration, abdominal bloating and discomfort will be
 treated symptomatically, and the rewards potentially much outweigh the risks.

 Persons with mental disabilities will be excluded. If the study is a success, this may
 dramatically reduce mortality at Genesys and elsewhere. The Centers for Disease Control
 estimates that over 14,000 patients die in the USA annually from c.diff infection induced
 diarrhea. The investigators couldn't locate worldwide numbers, but clearly significant, and a
 reduction in those deaths through an effective, widely available, inexpensive treatment
 should be welcome everywhere.

 Informed decision-making:

 Study eligible patients will be approached by the study physicians. The study will be
 explained to the patient and their family when present. The consent form will be provided to
 the patient and they will be given time to ask questions and read over the consent form. The
 investigators informed consent form is attached. Patients who agree will be enrolled into the
 study by the study physicians.

 Gender Issues:

 The investigators plan to include women and men alike in the study. When the investigators
 analyze the data, the investigators will determine any significant differences in outcomes
 based on gender, and report these.
Inclusion Criteria:

 -  18 years old or older male or female testing positive for c. diff

 Exclusion Criteria:

 -  Pregnancy Less than 18 yrs of age Those sick enough to require surgery at diagnosis
 Severe ileus or small bowel obstruction