Fecal Microbiota Transplants: Overcoming the Barriers of Implementation

By Amy Myers, RN, MSN, ACNS-BC, CNS-CP, CGRN, CAPA

Fecal transplants have been in existence since the fourth century and used to treat ailments such as diarrhea, food poisoning and various other gastrointestinal symptoms. The first fecal transplant performed  in the United States was done in 1958 for pseudomembranous colitis and in 1983 for Clostridium difficile (Brandt and Aroniadis, 2013; Eiseman, Bascom, Kauvar, 1958). It is hard to believe that a proven treatment that was performed centuries ago took so long for us to adopt. Simply stated, these proven treatments are known as evidence-based care, which is utilizing the best clinical evidence to guide practice for effective patient care. Although empirical evidence exists that proves efficacy, there are still many barriers in place at institutions that hinder or delay a new process. Some of these barriers include resistance to change, lack of resources, knowledge deficit, and lack of organizational support. In this article I am going to give insight to what barriers I faced while implementing a new process in the hospital where I work as a clinical nurse specialist.

Fecal microbiota transplant (FMT) has names such as fecal biotherapy, bacteriotherapy, or fecal transplant. FMT is the transfer of feces from one person to another to alter the fecal microbiome in a patient to treat certain diseases. Currently, in the United States, FMT is only Food and Drug Administration (FDA)-approved to treat C. difficile, which is a Gram-positive, spore-forming anaerobic bacillus found in normal gut flora. However, it was not recognized until the late 1970s that C. diff was linked to pseudomembranous colitis (Bartlett, Chang, Gurwith and Gorbach, 1978). From 1999 to 2004 the mortality from C. diff infections has risen from 5.7 to 23.7 deaths per million in the U.S. (Patel et al., 2013).

Infections from C. diff are at an alarming rate of 500,000 to 3 million cases a year in the U.S. with an estimated cost of $3.2 billion to hospitals and long-term care facilities (Brandt and Aroniadis, 2013). A hospital environment is not the main source where C. diff is contracted anymore, with over one-quarter being community acquired, and having various resistant strains developing. The U.S. is not the only country with C. diff on the rise; Europe, Canada and Korea have had increases as well, making C. diff a global concern (Rohlke and Stollman, 2012). FMT is utilized as a second line of treatment for patients that have been initially treated for outbreaks of C. diff with metronidazole, fidaxomicin, vancomycin or a combination of these (Rupnik, 2015). The FDA has only approved FMT as an investigational treatment when a C. diff patient has been treated with traditional pharmacologic therapies has failed or the patient develops severe pseudomembranous colitis (Bakken et al., 2011). When efficacy of FMT was recognized and studies began, the FDA considered these fecal treatments a drug and required practitioners to fill out an investigational new drug permit (IND) that would take up to eight hours to complete and several weeks to get approved, thus delaying treatment for many patients. Currently, the FDA does not require an IND and stated it will exercise “enforcement discretion” granted physicians obtain a proper consent with FMT treatments (FDA, 2013).

Patients at risk for developing C. diff are adults that are older, immunocompromised, have inflammatory bowel disorders, multiple comorbidities, frequent hospital stays, and/or on an antibiotic regimen (Leffler and Lamont, 2015). In my experience there are more and more patients requesting and welcoming FMT due to the decrease in quality of life, debilitation that has occurred from C. diff, and cost of antibiotic treatments. The increased incidence of C. diff has created a need for an effective treatment other than the multiple quantities of antibiotics that currently are becoming less and less effective. Refractory or recurrent C. diff (RCDI) tends to reoccur 6 percent to 50 percent of the time with traditional antibiotics compared to an over-90 percent cure rate with FMT (Rohlke  and Stollman, 2012). What makes FMT the treatment that is superior to traditional antibiotic is that does not decrease the cure rate for C. diff, even after subsequent doses unlike subsequent treatment with antibiotics. Fecal bacteriotherapy can be administered by enema, nasogastric tube, upper endoscopy or colonoscopy. All of these routes have different risks and benefits; however, the colonoscopy is considered the first line of therapy for patient efficacy and satisfaction (Rohlke and Stollman, 2012; Brandt  and Aroniadis, 2013). Feces can be donated by an immediate family member, close friend, intimate partner, or from a donor bank. Donor screening is very extensive and is guided by FDA recommendations but, to date, the only requirements from the FDA is that a special consent be included with a confirmed diagnosis of RCDI.

FMT Implementation
In May 2014, a colleague introduced me to the opportunity to perform the first FMT in Alaska. Since there were no other facilities in the state that performed FMT, it was very important for me to be a patient advocate and implement this treatment. I immediately contacted the physician who was requesting the FMT treatment and confirmed I would help get this instituted. The physician then scheduled the colonoscopy with FMT for five days later. I thought five days was more than enough time to get FMT started. Unfortunately it was not as easy as I imagined. I was very naive to think that everyone else would be as excited as I was to perform the first FMT in the state.

I performed extensive research on the topic by reviewing literature and protocols from other facilities to demonstrate the safety and efficacy of FMT. I then contacted the lab, perioperative leadership, and endoscopy management to gain buy-in and approval for the first FMT to occur. I received initial support from the director of nursing practice, lab supervisor and endoscopy manager; however, other perioperative and laboratory leadership felt there was not enough information and the legal risk was too high for implementation of FMT treatment in such a short time and instructed me to cancel the procedure. I then had to contact the physician and have the procedure rescheduled to a later date until I could gain approval to perform the FMT. Although I could understand the concerns from the hesitant leadership, I knew that this patient was in great need of the FMT treatment, the research was evidence-based, and the protocol that I developed was safe. I went back to the director of nursing practice to guide me in discussing the existing fears and concerns with perioperative and laboratory leadership. 

A lot of discussion took place over the next two days. Perioperative leadership agreed that I could proceed to perform this one treatment as long as I could get the lab to assist with the process. The laboratory leadership still was against assisting in the FMT and stated there needed to be an approved process and protocol in place. The lengthy, standard hospital approval process could take as long as six months. An alternate protocol was then developed to only include the endoscopy staff in the management of the FMT process to include reconstituting the donor specimen in the department. I presented the information to the perioperative leadership and once again was told it was too high of a legal risk for nursing and that the FMT would not take place. Since we needed to help this patient and it was the right thing to do, I presented the option to the endoscopy supervisor that I would do the procedure, and she agreed to assist. We decided that we would perform the procedure on a weekend so that we could validate the process and protocol that was developed. The director of nursing practice, the endoscopy manager and perioperative leadership were all finally in agreement that the FMT could take place.

Now that we could perform the procedure I met with the endoscopy supervisor to devise a plan and gather supplies for Saturday’s case. A few of the suggested supplies for mixing the specimen included using a blender, shaker, potato masher, tongue blade, gauze, kitchen strainer, coffee filter, 60 CC slip tip syringes, 500 mL of normal saline (NS), and/or tap water. We decided to use a blender and a kitchen strainer for the first treatment, not knowing how difficult it is to mix fecal specimen. These were purchased at a local department store that equaled approximately $26. Other supplies needed were 1,000 mL bottle of NS, seven slip tip syringes, a large specimen container from the lab, and personal protective equipment (PPE).

When nurses and other staff from the unit heard about the FM case, they had concerns. Several staff thought it was gross and just another process they would need to learn. Others were worried about the cost to the patients and if insurance would cover the FMT treatments. Since the nurses did not have all the information, I set up a meeting to provide education about FMT, the proposed protocol, and to welcome any ideas.  For this particular case just-in-time training occurred to the nurses who would prepare and recover the first FMT patient. I later provided education for the preoperative and postoperative areas to gain additional support, buy-in, and validate competence.

I contacted the patient to perform a thorough preoperative assessment, get the donor information, provide education, and ensured all questions were answered. The physician and I spoke earlier in the week to validate the patient and donor lab work was completed and that the investigational consent was developed to meet the FDA requirements. The physician confirmed that all of this was complete and sent the information to be put in the patient’s chart.

The patient and donor arrived on the day of the procedure and brought the fresh donor specimen in a Tupperware container that was too big to fit in any of the department’s biohazardous bags. The specimen was taken to the endoscopy department in a makeshift biohazardous bag and placed in a blender with 500 mL of NS. The manager and I donned PPE and mixed the specimen until it was a slurry-like consistency. The fecal matter was then poured into a lab bucket through the kitchen strainer. The specimen was easy to draw up into six syringes and instill during the colonoscopy. Another challenge was that the odor of the specimen ruminated throughout the department, which we knew would pose a challenge for mixing the matter for future FMTs. The patient tolerated the procedure without any complications. I followed up by phone with the patient post-procedure at three days, two weeks and one month post-treatment. The patient stated immediate relief from the C. diff symptoms and did not need any further pharmacologic treatment.

Overcoming Additional Barriers and Finding Success
Even though the first FMT was a success, there were additional barriers that I faced over the next few months to gain approval for a standardized process. I met with the lab several times, presenting evidence that best practice is that the specimen should be mixed in the hood within the microbiology lab. Just when I did not know what else that I could do to gain support and buy-in from the lab, there was one microbiology supervisor who spoke up and voiced support for this process. With her support, the lab agreed to be part of the process. The supervisor later confided in me she was not going to support the process but after hearing the evidence and how it helped the patient, she completely changed her mind. The next four specimens were mixed in the microbiology hood with her assistance. The protocol was finalized and approved by the policy and medical committee. It was a long process but worth it, knowing that patients have the access to this innovative treatment in Alaska.

The next request was to use a fecal bank from outside the state instead of donor feces. Using the fecal bank would expedite treatment and pose a lower cost to the patient. Research supports the use and efficacy of using a fecal bank but one concern posted was the stability and viability of the specimen due to our geographical challenges. The company that provided the fecal specimens validated transport could take place in 24 hours that the temperature would be regulated. There were no barriers to implement the fecal bank specimens with support from perioperative services, purchasing, the operating room, and the lab. Utilizing the fecal bank has been in place for a little over three months with much success. The fecal bank makes FMT available on short notice,  which allows our facility to provide inpatients with easier access to treatment, does not require any additional outside supplies, and has proven to lower the cost to the patient. The best part is that the lab no longer needs to mix donor specimens and I do not have to buy any more blenders.

The Future of FMT
There are other conditions that could be cured by FMT but have not yet been approved by the FDA. With more studies and investigation there could be the possibility of using FMT or even biotherapy pills as a first line treatment decreasing antibiotic use could be in the future (Baron and Kozarek, 2013; Harrison, 2013). Although change is difficult, nurses must act as change agents and patient advocates to guide others to adopt best-practice treatments in a timely manner. Working together, being open to change, and not giving up will make the difference to you personally, the institution at which you work, and most importantly, the patient. 

Amy Myers, MSN, RN, ACNS-BC, CNS-CP, CGRN, CAPA, is director of the GI service line at PAMC-Providence Alaska Medical Center, and has served as an advanced practice nurse in surgical services for the last two years. She graduated from Kent State Nursing Program with an ADN in 1992, going on to obtain her BSN and MSN from Walden University in 2011 and a post-master’s as an adult clinical nurse specialist in 2013. Her specialties include surgery and gastroenterology. She addressed the topic of fecal transplants at the SGNA’s national conference in May 2015.

References:
Bakken, J. S. et al. (2011). Treating clostridium difficile infection with fecal microbiota transplantation. Clinical Gastroenterology and Hepatology, 9(12):1044-1049. doi: 10.1016/j.cgh.2011.08.014
Baron, T. H. & Kozarek, R. A. (2013). Fecal microbiota transplant: we know its history but can we predict it’s future? Mayo Clin Proc. 88 (8):782-785. http://dx.doi.org/10.1016/j.mayocp.2013.06.007 
Bartlett, J. G. et al. (1978). Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. The New England Journal of Medicine, 298(10):531-534
Brandt, L. J. & Aroniadis, O. C. (2013). An overview of fecal microbiota transplantation techniques, indications, and outcomes. Gastrointestinal Endoscopy, 78, 240-248. doi:10.1016/j.gie.2013.03.1329
Eiseman, B. et al. (1958). Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery, 44(5):854-859Leffler, D. A. & Lamont, T. (2015). Clostridium difficile infection. The New England journal of Medicine, 1539-1548. doi: 10.1056/NEJMra1403772
Food and Drug Administration [FDA]. (2013). Guidance for industry: enforcement policy regarding investigational new drug requirements for use of fecal microbiota for transplantation to treat clostridium difficile infection not responsive to standard therapies. Retrieved from www.fda.org
Harrison, L. (2013). Fecal transplant pills effective for c difficile. Retrieved from www.medscape.com/viewarticle/812079
Patel, N.C. et al. (2013). Fecal microbiota transplant for recurrent clostridium difficile infection: mayo clinic in arizona experience. Mayo Clinic Proceedings, 88(8):799-805. doi:10.1016/j.mayocp.2013.04.022
Rohlke, F. & Stollman, N. (2012). Fecal microbiota transplantation in relapsing clostridium difficile infection. Theraputic Advances in Gastroenterology, 5(6):403-420. doi: 10.177/1756283X12453637
Rupnik, M. (2015). Toward a true bacteriotherapy for clostridium difficile infection. The New England Journal of Medicine. Retrieved from www. nejm.org