FECAL TRANSPLANT, also known as fecal bacteriotherapy, is probably the most headline-grabbing treatment of Clostridium difficile-associated disease (CDAD). Building on the approach of probiotics, fecal bacteriotherapy entails using feces as medicine. Although doing so goes against most of western medicine's basic tenets, experts in infectious diseases and gastroenterology find merit in the procedure. In fact, at the 48th Annual Meeting of the Infectious Diseases Society of America, two leaders in the field of CDAD debated not on whether to do fecal transplant, but how...and in what circumstances.1
Fecal bacteriotherapy targets bacterial interference within the bowel. C. difficile, an anaerobic, Gram-positive, spore-forming bacillus, invades and colonizes the gastrointestinal tract. Infection may precede or proceed gut insult from events such as antibiotic therapy or chronic Salmonella infection. In cases of chronic C. difficile, mainstream therapy usually fails and the patient experiences recurrent diarrhea, abdominal pain, nausea, vomiting, and bowel inflammation. Introducing normal bacterial flora from a healthy donor allows the patient's colon to recolonize with positive bacterial flora.
To date, there have been just over 350 fecal transplants to treat CDAD.2 The first reported procedure for recurrent infection was published in U.S. medical literature in 2003, just as C. difficile illness rates were increasing, along with the strain's pathogenicity. In this study, 18 subjects had the feces administered through a nasogastric tube.3 Now, most fecal transplants (80%) are administered through colon oscopy. No randomized control trial comparing the two methods of administration has been conducted and published, but reported outcomes appear similar. Note, though, that methodological differences and patient selection criteria prevent either approach from claiming treatment rates as comparable, superior, or inferior to the other approach.
Some clinicians claim that colon oscopy infusion is more difficult and strenuous, but that the nasogastric route (while safe and time efficient) isn't as effective if the patient has limited passage of liquids through the intestinal tract. Obviously, infusion via the nasogastric route offers patients the advantage of the donor material reaching the entire intestinal tract.4 Fecal enema is another way to repopulate the gastrointestinal tract to prevent C. difficile infection reoccurances. (See A nurse's account: Fecal bacteriotherapy at work.) Any one administration method—nasogastric tube, colonoscope, or enema—isn't superior to the other in preventing infection recurrence.
A closer look at CDAD
C. difficile is a bacterium in which certain strains produce a toxin that can cause a diarrheal illness. This diarrheal episode can range from mild to psuedomembranous colitis, toxic megacolon, sepsis, and even death. One predictor of the severity of the disease is the age of the person; older adults have more severe outcomes.5 Another predictor is the strain with which the patient is infected. Some strains produce significantly more toxins than others, with a corresponding increase in negative outcomes.
The number of cases of CDAD has risen dramatically.6 There are now more cases identified in the acute care setting, skilled nursing facilities, the community, and even in children.7,8 The reasons for this epidemic are multifactorial and include an aging population in the industrialized world; use of broader-spectrum antibiotics; mutations in some strains of C. difficile (making them even more pathogenic); the presence of pathogenic strains of C. difficile in the food supply; and newer, superior tests for identifying pathogenic strains of C. difficile.9–11
Although rates vary by strain, patient age, and other risk factors, approximately 20% of all patients will develop another episode of C.difficile infection within 180 days of antibiotic therapy discontinuation. The risk of relapse increases with each recurrence: up to 60% after the third recurrence.12 It's unclear why recurrence happens. Three possible explanations are (1) treatment failure to eliminate vegetative C. difficile in the patient's intestines, (2) reinfection of the patient with C. difficile, and (3) spore recrudescence (persistent spores from the initial infection). In most situations, the clinician will never know if the patient is suffering from a relapse or a new infection with a different strain of C. difficile.
Approximately half of all patients experiencing a relapse of C. difficile infection within 2 months are actually infected with a new strain of C. difficile. In these cases, disease control practices are key to preventing recurrence. Appropriate measures include adequate hand hygiene with soap and water before and after patient contact, as spores are resistant to alcohol. When the patient is infected with the same strain of C. difficile, the prevention may not be as simple. One important step to help derail reinfection is to ensure the patient's environment is clean.
C. difficile is a spore-forming organism that only a few disinfectants are capable of killing. Bleach is the most common disinfectant capable of accomplishing this task. However, bleach can damage equipment and surfaces, which is why the CDC, Association for Professionals in Infection Control and Epidemiology (APIC), and Society for Healthcare Epidemiology of America (SHEA) sometimes caution against the potent sanitizer.13–15 Contact time to kill the spores takes about 10 minutes with liquid bleach.
Boosting the patient's immune system response to the C. difficile toxin A (the most pathogenic toxin C. difficile produces) is one promising approach to reducing C. difficile infection recurrence. Studies have shown that patients develop an immunoglobulin M antitoxin-A when initially ill and later an increase in immunoglobulin G (IgG) antitoxin-A as they recover. In one study, those having the highest IgG antitoxin-A were 44 times less likely to have a recurrence of C. difficile infection than those with a lower level IgG response.16 This research has led to the development of an IgG antitoxin-A vaccine that, while still in trial, has offered some promising results.17
Another possible option for avoiding recurrence is administering probiotics—normal organisms found in gut flora that fight C. difficile. Literature, however, has shown mixed results regarding probiotics usage for preventing C. difficile infection and its recurrence.18 Two main reasons are that the bacterial count in probiotics is unknown, and the delivery technique is inefficient.19 Using probiotics isn't without risk; in some populations probiotics have been associated with bactermia, fungemia, and mortality.20,21 But, in cases where the dose is carefully measured and the selection is much more rigorous, infection has been prevented.19
Selection criteria, candidates, and donors
Although there are no clear guidelines on when to perform a fecal transplant, growing consensus is to attempt it only after the third or fourth C. difficile infection recurrence. Other selection criteria for candidates remain unclear.
With that said, donor selection criteria have increasingly developed. Fecal donors require more extensive testing than blood transfusion donors. Physician preference is for family members to donate, although healthy volunteers are also viable candidates. Fecal donors must go through routine testing for bloodborne pathogens, as with blood donors, including HIV-1 and HIV-2, syphilis, and hepatitis A, B, and C (which isn't generally thought of as a bloodborne pathogen but can be transmitted oral-fecally).
Additional tests are then conducted on the donor's stool for toxin-producing strains of C. difficile and enteric bacterial pathogens, such as those causing salmonella or shigella. Lastly, an ova and parasite test is done to rule out enteric parasites. Some physicians also order blood tests for Strongyloides and Entamoeba and screening for Cytomegalovirus, Epstein-Barr virus, and human T-lymphotropic virus. With these additional tests comes screening to determine patient history for or symptoms of irritable bowel syndrome, abnormal bowel movements, and/or abdominal complaints—all predisposing factors for transmissible diseases and a travel history. No cases of disease transmission have been reported from donations undergoing these screening approaches.
With so few fecal transplants and so little published data, physician preference and opinions are largely the basis for local hospital or gastroenterology clinic protocol development. Stool preparation is one area where the practice is much more standardized, with only two authors reporting slight variations. (One researcher homogenized the stool with whole pasteurized milk and another prepared the sample in an anerobic cabinet.22,23) Otherwise, reported practice is as follows: obtain the stool no more than 6 hours before transplantation; the older the stool, the less its biome reflects that of a healthy individual's stool. Soft stool is the preferred donation, mainly for ease of processing and administration. (It should weigh about 30 g or be 2 cm in length.) Transfer the stool to a blender designated for the task, then add 50 to 70 mL of saline. Turn the blender on using the slowest speed and then gradually move to the highest setting. After 2 to 4 minutes, the stool should be smooth. Strain the mixture in a paper coffee filter, allowing adequate time for the slow filtration to complete. Repeat this coffee filter process.
Preparation of the stool transplant recipient tends to vary. Some articles report giving the patient 4 days of oral vancomycin before the transplant, the last dose given the night before. Others state that the patient doesn't need antibiotics. Despite a few outliers, it's generally agreed upon that the patient shouldn't be on antibiotics at the time of the transplant, as this would potentially kill the normal intestinal flora needed to help combat infection.
Future fecal treatments
Amazingly, CDAD may not be the only illness that's ultimately treated with feces. In 2010 at the European Association for the Study of Diabetes, one researcher reported improved peripheral insulin sensitivity when patients with metabolic syndrome received feces from healthy lean donors compared to those who had autologous fecal transplants.24 Other researchers are investigating fecal transplants for the treatment of irritable bowel syndrome.
Despite western medicine's initial reaction to fecal bacteriotherapy, it's becoming increasingly popular among healthcare providers—a successful stool transplant was reported as early as 1958.25 Fecal bacteriotherapy may not be a mainstream treatment yet, but with continuing research and promising patient outcomes, it's gaining credibility.
A nurse's account: Fecal bacteriotherapy at work
By Jeffery Forehand, MSN, RN-BC, clinical coordinator, and Janice Wynn, RN-BC, director, Southeast Alabama Medical Center
When I admitted my new patient, Mrs. T, to room 572 with a diagnosis of relapsing Clostridium difficile infection (CDI), I read the admission orders as always, but I couldn't believe what I saw. Outside the room I reread the physician's order, aloud this time. “Probiotic therapy as follows: obtain a sample of the husband's stool and mix it with 500 cc of normal saline in a blender. Then strain the mixture through a coffee filter. Dilute the filtered fecal suspension to 1000 cc with additional normal saline and administer it to the patient via enema. Encourage the patient to hold the enema as long as possible, at least 15 minutes.” I asked a nearby nursing colleague to double-check the order with me. My colleague and I both looked at each other, bewildered. Could this order be accurate? Neither my co-worker nor I had ever heard of this type of therapy. I immediately placed a phone call to the physician to clarify the order. Before I could even speak, he asked if I had called in regard to Mrs. T's orders. After responding yes, he explained fecal bacteriotherapy and the results he hoped to achieve.
I can't begin to explain the thoughts that ran through my mind. I was unsure about how to explain the procedure to the patient. Eventually I decided the best method was to be straightforward. Much to my relief the patient stated she was well aware of what the physician had ordered and would do anything to relieve her current condition. She informed me of how her health had declined over the past 6 months due to her chronic CDI and accompanying diarrhea and dehydration. She had tried every available treatment without success and would do anything to have her life back.
After leaving the patient's room I realized the next task was actually preparing the fecal suspension for administration. (I informed my nurse manager of the situation and she provided a dedicated blender.)
After obtaining a sample of the husband's stool, the rest of the preparation process proved to be more of a challenge than I thought. The donor stool wasn't blending well and, with physician approval, I added additional normal saline. After finally getting the correct consistency, I began straining the fecal suspension through a coffee filter, which became quite an ordeal. The donor stool wasn't thin enough to pass through the filter. By this time, several staff members were involved in making this therapy a success. A co-worker suggested trying a kidney stone filter, which worked and produced a dark, watery solution. Finally, I approached the patient with the prepared enema. She graciously asked what she could do in order to help with the process. She also thanked the staff many times for going through so much trouble for her.
A few weeks later, we heard that the treatment was successful. We were extremely excited to be part of the first successful fecal transplant in our facility.
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