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Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience
ARTICLE IN PRESS American Journal of Infection Control ■■ (2016) ■■-■■
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American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Original Research Article
Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience Amy L. Pakyz PharmD, PhD, MS a,*, Leticia R. Moczygemba PharmD, PhD a, Lynn M. VanderWielen PhD, MPH b, Michael B. Edmond MD, MPH, MPA c a
Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA Department of Family Medicine, School of Medicine, University of Colorado, Aurora, CO c Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA b
Key Words: Qualitative study fecal bacteriotherapy
Background: Although effectiveness of fecal microbiota transplantation (FMT) has been adequately documented, the patient experience of undergoing FMT has not. Methods: We carried out a qualitative interview study using semistructured questions relating to aspects of health pre-FMT, during FMT, and post-FMT periods with 17 participants. Inductive coding was used to identify core themes during the periods. Results: Pre-FMT themes included physical (continuous diarrhea and weight loss), mental (depression, wanting to die, and fear), quality of life (unable to perform normal activities), social support, and financial (medication costs) factors. Provider resistance/limited awareness were barriers to FMT. Participants reached a tipping point, experiencing feelings of hopelessness, which led them to pursue FMT. During FMT, participants commented on lack of a so-called ick factor. During the posttreatment period, participants experienced symptom relief, but had residual fears. Patient activation was present during all phases, including information seeking and empowerment. Conclusions: During the pre-FMT period, participants experienced extreme discomfort and encountered FMT barriers. Undergoing FMT was reported as easy but residual fear remained. There were displays of patient activation at all FMT time periods, including the seeking of FMT. Participants could have benefited from having undergone FMT sooner, demonstrating a need for improvement in provider education and health system barriers regarding FMT. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Clostridium difficile is the most common organism to cause health care-associated infections, causing infectious diarrhea mainly in patients receiving antibiotic agents that alter the normal gut bacteria.1,2 In 2011, C difficile caused almost half a million infections and nearly 30,000 deaths.3 The North American Pulsed Field type 1 strain is attributed to an increase in disease severity and recurrence.4 Between 10% and 58% of patients experience recurrent infection, with higher proportions in those aged 65 years and older.5,6 For every recurrence, there
* Address correspondence to Amy Pakyz, PharmD, MS, PhD, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, 410 North 12th St, PO Box 980533, Richmond, VA 23298. E-mail address: [email protected] (A. Pakyz). Fecal microbiota transplantation is classified as an investigational drug by the US Food and Drug Administration. ALP is supported by funding from the Agency for Healthcare Research and Quality (grant No. K08 HS018578). ALP has served on an advisory board for Cubist Pharmaceuticals, and MBE serves on the Clinical Advisory Board of OpenBiome.
is an increased risk of further recurrences, leading to multiple diarrheal episodes and further treatment with vancomycin or fidaxomicin.7-9 An emerging treatment for recurrent C difficile infection, defined as a C difficile infection episode that occurs ≤8 weeks after the onset of a previous episode, provided that symptoms from the earlier episode resolved,1 is fecal microbiota transplantation (FMT), which involves donor or synthetic stool administration via oral administration, a nasogastric tube, colonoscopy, or enema, to reestablish gut microbiota.10-13 A randomized controlled trial evaluated FMT for the treatment of C difficile infection in 43 patients who had a relapse after receiving at least 1 course of treatment of either vancomycin or metronidazole. Patients were randomized to 1 of 3 treatment arms: duodenal FMT with vancomycin and bowel lavage, vancomycin and bowel lavage with no FMT, and a standard vancomycin regimen. The study ended upon interim analysis because the results showed that FMT had a higher response rate versus vancomycin with bowel lavage and versus vancomycin alone (81%, 31%, and 23%, respectively; P < .001 for both comparisons to FMT).13
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.01.018
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Although FMT success in resolving recurrence is well documented, the patient perspective regarding the effect of FMT on physical and mental health has not been fully considered. It was reported that patients without C difficile infection who were surveyed would consider FMT as an option in hypothetical case scenarios,14 and patients who do undergo FMT recommend the procedure to others.15 Yet, significant barriers to FMT exist, including logistical issues and belief that patients will find FMT unappealing.16,17 Patients with a first C difficile episode have previously revealed that they experienced physical and emotional distress, such as diarrhea and isolation, and were prevented from participating in usual activities.18 The experiences of patients with recurrent C difficile infection who have undergone FMT have not been fully described. Given that FMT is an emerging therapy, we aimed to document the influence that recurrence had on patients’ lives from the time period leading up to FMT through the period after. We also aimed to capture the experience of undergoing FMT in terms of the barriers that patients encountered and the effect that FMT had on quality of life. MATERIALS AND METHODS Study population For this qualitative study, purposeful sampling19 was used to select patients who had undergone an FMT via nasogastric tube in an ambulatory care setting at 1 institution, who had varying responses regarding duration of C difficile disease before undergoing FMT, whether stool was obtained from a donor or stool bank, and the number of FMTs undergone. A total of 30 patients were identified who underwent FMT between March 2012 and June 2014 and were considered able to conduct an interview via telephone. Patients with severe or life-threatening conditions at the time of FMT were excluded. Patients were recruited by sending an invitation through postal mail, and interested patients contacted a study investigator to enroll. Semistructured, audio-recorded interviews that lasted between 30 and 45 minutes focused on aspects of physical and mental health, as well as quality of life, finances, and social support during the time periods before and after FMT, and on the FMT experience itself. The conduction of interviews was continued until the sample included patients with varying FMT-factors as described above. Qualitative analysis Transcripts were generated of the audiorecorded telephone interviews and compared with the original for accuracy. The texts were read independently by multiple reviewers to isolate meaningful units, which were then subjected to several stages of inductive coding for thematic development.19 The findings were reviewed after the first 5 were coded and a list of agreed-upon codes was generated. The process was repeated with all transcripts until the list of codes was completed along with the phrasing for each code label. Themes were then identified from this procedure. The coders used the interview topic guide, composed of questions pertaining to physical and mental health symptoms, quality of life, social support, and finances, in the context of different time periods (pre-FMT, FMT, and post-FMT) as a framework19 for presentation of resultant themes. The closing question, “Is there anything else related to this topic that you would like to tell me about?” was analyzed separately. Regular meetings were held among the coders to finalize main themes that were reviewed by a content expert (MBE). Discrepancies were resolved using a consensus-building approach, and when necessary, majority agreement among the reviewers (2 out of 3) was used to make final decisions. The study was approved by an institutional review board.
RESULTS Participant characteristics A total of 17 individuals participated. Sixteen telephone interviews were performed between July and September 2014; 1 was carried out with the father of a participant who was a child, and 1 was with a participant’s daughter because the participant was in early stage dementia, which had begun since the time of FMT treatment. One additional hearing-impaired participant responded via written responses. Table 1 displays participant characteristics. The typical participant was a retired, 63-year-old white woman who had diarrhea for 7.2 months and a 25-lb weight loss before selfreferring for FMT and traveled 73 miles to the procedure site. The majority of participants (82%) underwent 1 FMT and nearly half of participants (48%) received donor stool from a first-degree relative or spouse. There were several themes identified in the pre-FMT, FMT, and post-FMT periods concerning physical and mental health, quality of life, social support, and finances. We also identified a distinct tipping point period that led up to FMT. Throughout all time periods patient activation behaviors, including empowerment and information seeking, were identified. Hibbard’s definition of patient activation— the ability to self-manage health and health care—was used as a guide.20 Figure 1 displays the FMT periods and identified themes. During the pre-FMT period, participants experienced difficulty in many aspects, including physical and mental. Participants had debilitating bouts of continuous diarrhea and abdominal pain, with 1 respondent stating, “Every time that I would have a bowel movement it felt like I had glass, and it felt like twisting, like you take a dishrag and twist it to get all the water out of it.” Appetite and weight
Table 1 Participant characteristics (n = 17) Characteristic Age, y Female White race Previously healthy† Retired‡ Mean duration of time between Clostridium difficile onset and FMT, mo Source regarding FMT option Physician referral Combination Internet search and physician referral Internet search by patient/friend/family member and self-referral Number of FMTs undergone 1 2 3 Donor relationship: First-degree relative Spouse Nonrelative OpenBiome stool bank Parent Weight loss, lb§ Distance travelled to undergo FMT, miles Number of months past FMT at time of interview
Value 63 ± 19 (7-83)* 15 (88) 17 (100) 10 (59) 12 (75) 7.2 (3-23)
1 (6) 2 (12) 14 (82)
14 (82) 2 (12) 1 (6) 5 (24) 5 (24) 1 (5) 9 (43) 1 (5) 25 (0-63) 73 (15-190) 16 (3-30)
NOTE. Values are presented as mean ± standard deviation (range), mean (range), or n (%). FMT, Fecal microbiota transplantation. *Interview with the 7-year-old patient was conducted with his father. †No recent history of hospitalization except elective procedures (such as cesarean section, hernia repair, or knee replacement surgery) or major medical diagnosis such as cancer. ‡Denominator out of 16, excluding the participant representing his 7-year-old son. § Three did not report.
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Fig 1. Themes identified in the different fecal microbiota transplantation (FMT)-related time periods. Examples of patient activation were evident throughout the pre-FMT, tipping point, FMT, and post-FMT periods.* *The symptoms and factors identified among the 6 pre-FMT themes before FMT may have differed among respondents in terms of order and extent of occurrence.
loss were also experienced. Profound weakness occurred, as explained by 1 respondent: “I was completely drained, I could barely drag myself to the bathroom, I literally had to hold on to things.” Sleep disturbances were common, with 1 respondent describing “I would try to stay awake so I would know when I had to go (to the bathroom) because if you couldn’t you had no prayer of getting there and then you would be swimming in it right in the bed.” Participants felt isolated and reported depressive symptoms, with some reporting they “would rather die” than live with C difficile infection: “I was so depressed that I really came home and I started talking to my family about dying because I really didn’t see how I was going to get out of this.” Patients feared they would spread the disease, which led to isolation and disengagement from social activities, with respondents conveying, “I couldn’t go out because I needed to constantly go to the bathroom” and, “I couldn’t get near people and mingle with them, I couldn’t possibly imagining myself using their bathroom and passing on the germs.” Patients also feared that they would never get better, “The worst part was that I was so afraid that I was never going to get better, that I had a drug-resistant bacteria that was unable to be treated.” Participants were not able to carry out normal activities of living and missed social commitments, as 1 respondent relayed: “I had arranged a family reunion in Denver, and I was the only person that didn’t get there.” In respect to social support, most patients had a high degree of support from family members and friends; however, dependence on others for tasks, such as meal preparation, made participants feel like a burden . . . “It consumes the family’s life because it requires a 24-hour caretaker.” Participants expressed frustration over receiving mixed messages from providers, as 1 respondent explained: “Different doctors tell you different things because 1 doctor put me on probiotics and said this is what you should be on; another doctor said that’s not going to help at all.” Participants also commonly faced barriers to FMT in the form of provider resistance and limited awareness, as expressed by 2 respondents: “I went to my general practitioner and said, what about this [FMT]? He laughed in my face and said, we’ve
gone a long way since the dark ages, we have medicine now” and, “Most doctors don’t know about the procedure . . . they think it’s voodoo or something . . . they don’t know where to send [you], there’s no place here to go.” Participants were influenced by high costs of treatment medications. “One month our drug bill was $10,000. Do you think that would affect most people?” and/or the inability to work: “It cost me 3 jobs—that was about $15,000—and they have not returned.” As quality of life decreased, patients became highly activated in their search for a solution to get better; their behaviors included information seeking and persistence regarding FMT pursuance. Participants spent a significant amount of time researching treatments, and thereby increased their confidence in directly asking their providers about FMT. As a result, patients were empowered to take ownership in their health and treatment options. Representative quotes for patient activation examples are presented in Table 2. Before FMT receipt, participants would reach a tipping point (Fig 1) at which the buildup of the burden of symptoms led to feelings of hopelessness about their options and their future. At this time, participants took initiative by seeking out FMT (ie, selfreferral) by contacting an FMT physician. Regarding the themes identified in the time period FMT, participants commented on how easy it was to undergo and the lack of a so-called ick factor, and that the stool donor faced the most anxiety. In the period postFMT, participants revealed that although there was a nearly immediate resolution of diarrhea, many experienced residual effects from having long-standing diarrhea, such as irritable bowel symptoms. Although physical symptoms were immediate, other effects took several months up to 1 year to resolve, including fears of recurrence. Other themes were the ability of the patient to resume daily activities and a display of gratitude toward the FMT-performing physician. Patient activation behaviors during these time periods included advocacy for FMT, accountability, and empowerment (Table 3). Representative quotes for identified themes from the tipping point, FMT, and post-FMT periods are presented in Table 3.
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Table 2 Examples of patient activation during fecal microbiota transplantation (FMT) periods Period
Activation type
Representative/supportive quotation(s)
Pre-FMT
Empowerment
Pre-FMT Pre-FMT
Information seeking Persistence
FMT Post-FMT Post-FMT
Empowerment Advocacy Accountability
“I called up my insurance company and yelled at them because they wouldn’t cover any of it [vancomycin].” “I had to fight with the doctor . . . they were going to put me back on [metronidazole] again, which is what I had been on the past 5 months.” “I had read up on it on the Internet and I basically knew there are 2 ways it was done, either through a colonoscopy or a nasal gastric tube. It made no difference to me how it was done I just wanted it done.” “I did a lot or research online and found that they were doing it [FMT] in countries like England and Australia, but I couldn’t find anyone here in the United States much less the East Coast. I just kept researching it for months. I don’t know if I typed in the right words or what, but all of a sudden [my doctor’s] name popped up. That was a Sunday and I called him first thing Monday morning.” “I said what do I have to lose. I can’t live like this . . . it’s an option [FMT] and I’m going for it.” “I want the whole world to know about the procedure, use my name, I would get on television and talk about it.” “I did go back to all these people who thought it [FMT] was a bogus thing . . . I went back face to face . . . I even called the director of the hospital. I said if this had not been done for my mother she probably wouldn’t be here because your physician didn’t do anything. I made sure when I left there they knew, because it could be somebody else who comes along and gets it as bad as she did.”
FMT, Fecal microbiota transplantation.
Table 3 Summary of themes identified during tipping point, fecal microbiota transplantation (FMT), and post-FMT periods Period
Themes
Tipping point
Hopelessness/frustration
FMT
Donor Easy/quick No ick factor Relief
Post-FMT
Residual symptoms Residual fear/caution
Resuming of daily activities
Gratitude toward physician performing FMT
Representative/supportive quotation(s) “I was out of options.” “So I was caught for about 5, 6 months in this spot where I was trying to decide whether to take vancomycin for the rest of my life, but life is not worth living with Clostridium difficile” “He [the donor] had performance anxiety.” “Abracadabra. It was you’ve got to be kidding me, is this all I had to do?” “But there is no smell, no taste, no after anything, there’s nothing to be afraid of or to be concerned about.” “I felt very, very, very shortly, like within a day or 2, I could feel that there was a difference in my body, my intestines weren’t tied up in a knot and screaming, and my body felt like it was actually going to survive.” “But to this day I still have—there are certain times where certain foods, if, I guess, they have a higher roughage or some level or something I’m not going to be happy. So I have to watch what I eat now.” “I won’t take antibiotics unless they are life or death. I will not.” “I still am very cautious about hygiene. I still have my husband using a different bathroom in the house than I am using.” “I had time to kind of say am I really better? You know, you’re very tentative, you’re afraid to make plans . . . all this weird mind game.” “It was like night and day because then I was off antibiotics and I felt like 100%. I was going back to the gym, back at work, absolutely no diarrhea at all.” “I was back to living, I was back to my friends, I was back to entertaining, we would go out to dinner with our friends and I wasn’t afraid, because with that C difficile there is a huge fear factor.” “I would stand on my head for him right now, as I think most of his patients would.” “He saved my life, because I have no doubt if I didn’t have the transplant I would be dead, because they had used every drug they could think of.”
Analysis of the closing interview question led to findings regarding anger toward the barriers that participants encountered, including those set by treating physicians and the Food and Drug Administration (in reference to a policy during a 2-month period in 2013 during which Investigational New Drug application approval was necessary by the FMT-treating physician).21 One participant stated, “I am angry that people were denied the opportunity to have it [FMT] done for them.” Frustration was evident from having residual symptoms and not having undergone FMT sooner, as expressed by 2 participants: “My hair was falling out . . . everybody who saw me said I looked horrible. I don’t understand why this isn’t offered sooner rather than later, because I think my recovery would have been quicker” and, “What I feel really sad about is that I wasn’t given this opportunity earlier in treatment . . . that my doctors out here in suburbia just thought they were going to medicate me forever.” The closing question also revealed several areas of participantoffered advice directed mainly toward FMT barriers, including that awareness should be increased regarding FMT as a treatment, of its effectiveness, and the need for more FMT providers. For example, regarding FMT as a treatment, 1 participant stated, “Maybe you let the vancomycin fail once and then use the [fidaxomicin], and then do the transplant, as opposed to [fidaxomicin] has to fail 3 times and then the other has to fail and finally, oh, we’ve got nothing else.” Another participant remarked, “Doctors need to understand that not everybody is going to be able to heal or get better from this infection
by [metronidazole] or vancomycin, you’ve got to think about the next plan of action.” Regarding FMT availability, 1 participant commented that “there’s not enough people doing these procedures.” DISCUSSION There were several insightful findings from participants’ experiences in undergoing FMT. In the time leading to FMT, participants experienced difficulty mentally, financially, and physically, and they needed to rely on support networks to carry out usual daily activities. Feelings of hopelessness about their condition and frustration stemming from encountering health system barriers to FMT led to a tipping point at which activated patients would initiate plans to undergo FMT. Immediate resolution of diarrhea was experienced; however, there were residual effects, such as fears concerning recurrence. During the post-FMT period, participants displayed further examples of patient activation, including willingness to serve as an FMT advocate to increase provider awareness, and taking measures to hold providers accountable. Participants advised that FMT should be offered sooner in the course of treatment, and that provider education is needed regarding FMT. Similar to our findings, previous reports of patient experiences relayed the physical aspects of C difficile infection,22 as well as feelings of depression and isolation, being worried about contagiousness, and the possibility of reinfection.18 We found that participants
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encountered multiple barriers to receiving FMT, including a lack of FMT providers, low awareness among physicians, and physician resistance. A survey administered to infectious diseases physicians about FMT showed that although the majority of those surveyed (80%) would consider FMT, logistical issues regarding fecal donor preparation and delivery and donor testing were commonplace.16 Another survey of physicians’ attitudes showed that among reasons cited for not offering FMT, 24% believed patients would find FMT unappealing, with 23% stating that institutional barriers were a problem, and 18% found FMT unappealing themselves.17 The majority of participants had to seek out FMT on their own initiative in our study. This aligns with findings by Zipursky et al,14 who found that among patients surveyed regarding their perceptions towards FMT, that although respondents deemed aspects of FMT unappealing, the majority selected it as a treatment for recurrence in hypothetical case scenarios. Among patients who have undergone FMT, it was reported that they had no concerns about any aspects of FMT.23 Patient activation behaviors, including information seeking, identifying treatment options, and having confidence to talk about treatment with providers,20,24 were commonly reported by participants. Our findings suggest that conditions such as C difficile infection that are quick-onset, debilitating, and that significantly influence daily activities and quality of life can rapidly motivate patients to take on activating behaviors. From the participant stories, patient activation behaviors appeared to increase as antibiotic treatment failed and patients were told they were out of options and thereby took to finding their own solution, including identification of the FMT provider, often through an Internet search conducted by the respondent or friend or family member, and self-referral to the FMT provider. The eagerness for which respondents embraced serving as advocates was also an interesting finding, driven, in part, by changes in FMT regulation by the Food and Drug Administration during the study period.21,25 Given that patient activation levels vary,20,24 it is important that all patients with recurrent C difficile infection are aware of options, including FMT, to make timely informed decisions about their condition. Although the respondents, on average, went 7.2 months between initial infection and FMT and multiple courses of pulsed/tapered vancomycin and or fidaxomicin, a guideline by the American College of Gastroenterology recommends FMT for a third recurrence after a pulsed vancomycin regimen.26 Further, as participants reported that they relied upon caregivers, mainly family members, to assist with day-to-day activities, caregiver support should be considered in the treatment plan. Those with low support may need assistance with transportation to appointments, delivery of medications, and arranging home delivery of groceries. This study has a few limitations. One is that the study sample represents relatively healthy participants who volunteered to undergo a telephone interview; the experiences may not necessarily represent those who are more severely ill, nor those who may have had a negative experience. Further, the results represent participant experiences in 1 FMT setting, and given the varying time spans between the undergoing of FMT and the interview among respondents, it is possible that respondent recall was influenced differentially by the amount of time that passed since undergoing FMT. Further, whereas thematic development through an inductive coding process was used to inform upon the experiences of respondents, it is possible that data saturation did not occur, meaning that the point where no new information was gathered with conduction of further interviews was reached.19 Finally, although depictions of the FMT experience were conveyed mostly by those who have undergone FMT, 2 of the interviews were carried out with family members who did not personally experience FMT.
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CONCLUSIONS Although activated patients may seek FMT for the treatment of C difficile infection recurrence and have resolution, the experiences of those undergoing FMT indicate the need for an effective treatment that can be delivered in a timely and consistent manner to avoid prolonged debilitating effects on physical and mental health. Although FMT effectiveness has been demonstrated with suggested indications for use and with few short-term adverse effects, and whereas FMT may be effective in decreasing C difficile contagiousness,12,26,27 participants frequently encountered barriers toward FMT and faced provider unawareness about FMT as a treatment option. Although there are promising treatments on the horizon, including synthetic stool substitute and C difficile nontoxigenic strain therapies,28,29 FMT currently remains the most viable option for resolution of recurrence, underscoring the need for increased consideration of and availability for FMT treatment.
References 1. Dubberke ER, Carling P, Carrico R, Donskey CJ, Loo VG, McDonald LC, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:628-45. 2. Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:1198-208. 3. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:82534. 4. See I, Mu Y, Cohen J, Beldavs ZG, Winston LG, Dumyati G, et al. NAP1 strain type predicts outcomes from Clostridium difficile infection. Clin Infect Dis 2014;58:1394-400. 5. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Fulop K, et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005;40:1591-7. 6. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis 2007;45:302-7. 7. McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol 2002;97:1769-75. 8. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, et al. Clostridium difficile infection in Europe: a hospital-based survey. Lancet 2011;377:63-73. 9. Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC, Franzos MA, et al. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol 2011;9:1044-9. 10. Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA 2014;312:772-8. 11. Hirsch BE, Saraiya N, Poeth K, Schwartz RM, Epstein ME, Honig G. Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent C. difficile infection. BMC Infect Dis 2015;15:191. 12. Brandt LJ, Aroniadis OC, Mellow M, Kanatzar A, Kelly C, Park T, et al. Long-term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection. Am J Gastroenterol 2012;107:1079-87. 13. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-15. 14. Zipursky JS, Sidorsky TI, Freedman CA, Sidorsky MN, Kirkland KB. Patient attitudes toward the use of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. Clin Infect Dis 2012;55:1652-8. 15. Khan MA, Sofi AA, Ahmad U, Alaradi O, Khan AR, Hammad T, et al. Efficacy and safety of, and patient satisfaction with, colonoscopic-administered fecal microbiota transplantation in relapsing and refractory community- and hospitalacquired Clostridium difficile infection. Can J Gastroenterol Hepatol 2014;28:434-8. 16. Bakken JS, Polgreen PM, Beekmann SE, Riedo FX, Streit JA. Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians. Anaerobe 2013;24:20-4. 17. Zipursky JS, Sidorsky TI, Freedman CA, Sidorsky MN, Kirkland KB. Physician attitudes toward the use of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection. Can J Gastroenterol Hepatol 2014;28:319-24. 18. Guillemin I, Marrel A, Lambert J, Beriot-Mathiot A, Doucet C, Kazoglou O, et al. Patients’ experience and perception of hospital-treated Clostridium difficile infections: a qualitative study. Patient 2014;7:97-105. 19. Patton MQ. Qualitative research and evaluation methods. 3rd ed. Thousand Oaks (CA): Sage Publications; 2002.
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20. Hibbard JH, Stockard J, Mahoney ER, Tusler M. Development of the patient activation measure (PAM): conceptualizing and measuring activation in patients and consumers. Health Serv Res 2004;39:1005-26. 21. Mole B. FDA gets to grips with faeces. Nature 2013;498:147-8. 22. Madeo M, Boyack M. Using the lived experiences of patients with Clostridium difficile infection to improve care. Nurs Times 2010;106:10-3. 23. Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 2003;36:580-5. 24. Hibbard JH. Using systematic measurement to target consumer activation strategies. Med Care Res Rev 2009;66(1 Suppl):9S-27S. 25. Ratner M. Fecal transplantation poses dilemma for FDA. Nat Biotechnol 2014;32:401-2.
26. Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 2013;108:478-98. 27. Lawley TD, Clare S, Walker AW, Stares MD, Connor TR, Raisen C, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog 2012;8:e1002995. doi:10.1371/journal.ppat.1002995. 28. Petrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D, Daigneault MC, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: “RePOOPulating” the gut. Microbiome 2013;1:3. 29. Gerding DN, Meyer T, Lee C, Cohen SH, Murthy UK, Poirier A, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA 2015;313:1719-27.
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American Journal of Infection Control
American Journal of Infection Control
j o u r n a l h o m e p a g e : w w w. a j i c j o u r n a l . o r g
Original Research Article
Fecal microbiota transplantation for recurrent Clostridium difficile infection: The patient experience Amy L. Pakyz PharmD, PhD, MS a,*, Leticia R. Moczygemba PharmD, PhD a, Lynn M. VanderWielen PhD, MPH b, Michael B. Edmond MD, MPH, MPA c a
Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA Department of Family Medicine, School of Medicine, University of Colorado, Aurora, CO c Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA b
Key Words: Qualitative study fecal bacteriotherapy
Background: Although effectiveness of fecal microbiota transplantation (FMT) has been adequately documented, the patient experience of undergoing FMT has not. Methods: We carried out a qualitative interview study using semistructured questions relating to aspects of health pre-FMT, during FMT, and post-FMT periods with 17 participants. Inductive coding was used to identify core themes during the periods. Results: Pre-FMT themes included physical (continuous diarrhea and weight loss), mental (depression, wanting to die, and fear), quality of life (unable to perform normal activities), social support, and financial (medication costs) factors. Provider resistance/limited awareness were barriers to FMT. Participants reached a tipping point, experiencing feelings of hopelessness, which led them to pursue FMT. During FMT, participants commented on lack of a so-called ick factor. During the posttreatment period, participants experienced symptom relief, but had residual fears. Patient activation was present during all phases, including information seeking and empowerment. Conclusions: During the pre-FMT period, participants experienced extreme discomfort and encountered FMT barriers. Undergoing FMT was reported as easy but residual fear remained. There were displays of patient activation at all FMT time periods, including the seeking of FMT. Participants could have benefited from having undergone FMT sooner, demonstrating a need for improvement in provider education and health system barriers regarding FMT. © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Clostridium difficile is the most common organism to cause health care-associated infections, causing infectious diarrhea mainly in patients receiving antibiotic agents that alter the normal gut bacteria.1,2 In 2011, C difficile caused almost half a million infections and nearly 30,000 deaths.3 The North American Pulsed Field type 1 strain is attributed to an increase in disease severity and recurrence.4 Between 10% and 58% of patients experience recurrent infection, with higher proportions in those aged 65 years and older.5,6 For every recurrence, there
* Address correspondence to Amy Pakyz, PharmD, MS, PhD, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University School of Pharmacy, 410 North 12th St, PO Box 980533, Richmond, VA 23298. E-mail address: [email protected] (A. Pakyz). Fecal microbiota transplantation is classified as an investigational drug by the US Food and Drug Administration. ALP is supported by funding from the Agency for Healthcare Research and Quality (grant No. K08 HS018578). ALP has served on an advisory board for Cubist Pharmaceuticals, and MBE serves on the Clinical Advisory Board of OpenBiome.
is an increased risk of further recurrences, leading to multiple diarrheal episodes and further treatment with vancomycin or fidaxomicin.7-9 An emerging treatment for recurrent C difficile infection, defined as a C difficile infection episode that occurs ≤8 weeks after the onset of a previous episode, provided that symptoms from the earlier episode resolved,1 is fecal microbiota transplantation (FMT), which involves donor or synthetic stool administration via oral administration, a nasogastric tube, colonoscopy, or enema, to reestablish gut microbiota.10-13 A randomized controlled trial evaluated FMT for the treatment of C difficile infection in 43 patients who had a relapse after receiving at least 1 course of treatment of either vancomycin or metronidazole. Patients were randomized to 1 of 3 treatment arms: duodenal FMT with vancomycin and bowel lavage, vancomycin and bowel lavage with no FMT, and a standard vancomycin regimen. The study ended upon interim analysis because the results showed that FMT had a higher response rate versus vancomycin with bowel lavage and versus vancomycin alone (81%, 31%, and 23%, respectively; P < .001 for both comparisons to FMT).13
0196-6553/© 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2016.01.018
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Although FMT success in resolving recurrence is well documented, the patient perspective regarding the effect of FMT on physical and mental health has not been fully considered. It was reported that patients without C difficile infection who were surveyed would consider FMT as an option in hypothetical case scenarios,14 and patients who do undergo FMT recommend the procedure to others.15 Yet, significant barriers to FMT exist, including logistical issues and belief that patients will find FMT unappealing.16,17 Patients with a first C difficile episode have previously revealed that they experienced physical and emotional distress, such as diarrhea and isolation, and were prevented from participating in usual activities.18 The experiences of patients with recurrent C difficile infection who have undergone FMT have not been fully described. Given that FMT is an emerging therapy, we aimed to document the influence that recurrence had on patients’ lives from the time period leading up to FMT through the period after. We also aimed to capture the experience of undergoing FMT in terms of the barriers that patients encountered and the effect that FMT had on quality of life. MATERIALS AND METHODS Study population For this qualitative study, purposeful sampling19 was used to select patients who had undergone an FMT via nasogastric tube in an ambulatory care setting at 1 institution, who had varying responses regarding duration of C difficile disease before undergoing FMT, whether stool was obtained from a donor or stool bank, and the number of FMTs undergone. A total of 30 patients were identified who underwent FMT between March 2012 and June 2014 and were considered able to conduct an interview via telephone. Patients with severe or life-threatening conditions at the time of FMT were excluded. Patients were recruited by sending an invitation through postal mail, and interested patients contacted a study investigator to enroll. Semistructured, audio-recorded interviews that lasted between 30 and 45 minutes focused on aspects of physical and mental health, as well as quality of life, finances, and social support during the time periods before and after FMT, and on the FMT experience itself. The conduction of interviews was continued until the sample included patients with varying FMT-factors as described above. Qualitative analysis Transcripts were generated of the audiorecorded telephone interviews and compared with the original for accuracy. The texts were read independently by multiple reviewers to isolate meaningful units, which were then subjected to several stages of inductive coding for thematic development.19 The findings were reviewed after the first 5 were coded and a list of agreed-upon codes was generated. The process was repeated with all transcripts until the list of codes was completed along with the phrasing for each code label. Themes were then identified from this procedure. The coders used the interview topic guide, composed of questions pertaining to physical and mental health symptoms, quality of life, social support, and finances, in the context of different time periods (pre-FMT, FMT, and post-FMT) as a framework19 for presentation of resultant themes. The closing question, “Is there anything else related to this topic that you would like to tell me about?” was analyzed separately. Regular meetings were held among the coders to finalize main themes that were reviewed by a content expert (MBE). Discrepancies were resolved using a consensus-building approach, and when necessary, majority agreement among the reviewers (2 out of 3) was used to make final decisions. The study was approved by an institutional review board.
RESULTS Participant characteristics A total of 17 individuals participated. Sixteen telephone interviews were performed between July and September 2014; 1 was carried out with the father of a participant who was a child, and 1 was with a participant’s daughter because the participant was in early stage dementia, which had begun since the time of FMT treatment. One additional hearing-impaired participant responded via written responses. Table 1 displays participant characteristics. The typical participant was a retired, 63-year-old white woman who had diarrhea for 7.2 months and a 25-lb weight loss before selfreferring for FMT and traveled 73 miles to the procedure site. The majority of participants (82%) underwent 1 FMT and nearly half of participants (48%) received donor stool from a first-degree relative or spouse. There were several themes identified in the pre-FMT, FMT, and post-FMT periods concerning physical and mental health, quality of life, social support, and finances. We also identified a distinct tipping point period that led up to FMT. Throughout all time periods patient activation behaviors, including empowerment and information seeking, were identified. Hibbard’s definition of patient activation— the ability to self-manage health and health care—was used as a guide.20 Figure 1 displays the FMT periods and identified themes. During the pre-FMT period, participants experienced difficulty in many aspects, including physical and mental. Participants had debilitating bouts of continuous diarrhea and abdominal pain, with 1 respondent stating, “Every time that I would have a bowel movement it felt like I had glass, and it felt like twisting, like you take a dishrag and twist it to get all the water out of it.” Appetite and weight
Table 1 Participant characteristics (n = 17) Characteristic Age, y Female White race Previously healthy† Retired‡ Mean duration of time between Clostridium difficile onset and FMT, mo Source regarding FMT option Physician referral Combination Internet search and physician referral Internet search by patient/friend/family member and self-referral Number of FMTs undergone 1 2 3 Donor relationship: First-degree relative Spouse Nonrelative OpenBiome stool bank Parent Weight loss, lb§ Distance travelled to undergo FMT, miles Number of months past FMT at time of interview
Value 63 ± 19 (7-83)* 15 (88) 17 (100) 10 (59) 12 (75) 7.2 (3-23)
1 (6) 2 (12) 14 (82)
14 (82) 2 (12) 1 (6) 5 (24) 5 (24) 1 (5) 9 (43) 1 (5) 25 (0-63) 73 (15-190) 16 (3-30)
NOTE. Values are presented as mean ± standard deviation (range), mean (range), or n (%). FMT, Fecal microbiota transplantation. *Interview with the 7-year-old patient was conducted with his father. †No recent history of hospitalization except elective procedures (such as cesarean section, hernia repair, or knee replacement surgery) or major medical diagnosis such as cancer. ‡Denominator out of 16, excluding the participant representing his 7-year-old son. § Three did not report.
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Fig 1. Themes identified in the different fecal microbiota transplantation (FMT)-related time periods. Examples of patient activation were evident throughout the pre-FMT, tipping point, FMT, and post-FMT periods.* *The symptoms and factors identified among the 6 pre-FMT themes before FMT may have differed among respondents in terms of order and extent of occurrence.
loss were also experienced. Profound weakness occurred, as explained by 1 respondent: “I was completely drained, I could barely drag myself to the bathroom, I literally had to hold on to things.” Sleep disturbances were common, with 1 respondent describing “I would try to stay awake so I would know when I had to go (to the bathroom) because if you couldn’t you had no prayer of getting there and then you would be swimming in it right in the bed.” Participants felt isolated and reported depressive symptoms, with some reporting they “would rather die” than live with C difficile infection: “I was so depressed that I really came home and I started talking to my family about dying because I really didn’t see how I was going to get out of this.” Patients feared they would spread the disease, which led to isolation and disengagement from social activities, with respondents conveying, “I couldn’t go out because I needed to constantly go to the bathroom” and, “I couldn’t get near people and mingle with them, I couldn’t possibly imagining myself using their bathroom and passing on the germs.” Patients also feared that they would never get better, “The worst part was that I was so afraid that I was never going to get better, that I had a drug-resistant bacteria that was unable to be treated.” Participants were not able to carry out normal activities of living and missed social commitments, as 1 respondent relayed: “I had arranged a family reunion in Denver, and I was the only person that didn’t get there.” In respect to social support, most patients had a high degree of support from family members and friends; however, dependence on others for tasks, such as meal preparation, made participants feel like a burden . . . “It consumes the family’s life because it requires a 24-hour caretaker.” Participants expressed frustration over receiving mixed messages from providers, as 1 respondent explained: “Different doctors tell you different things because 1 doctor put me on probiotics and said this is what you should be on; another doctor said that’s not going to help at all.” Participants also commonly faced barriers to FMT in the form of provider resistance and limited awareness, as expressed by 2 respondents: “I went to my general practitioner and said, what about this [FMT]? He laughed in my face and said, we’ve
gone a long way since the dark ages, we have medicine now” and, “Most doctors don’t know about the procedure . . . they think it’s voodoo or something . . . they don’t know where to send [you], there’s no place here to go.” Participants were influenced by high costs of treatment medications. “One month our drug bill was $10,000. Do you think that would affect most people?” and/or the inability to work: “It cost me 3 jobs—that was about $15,000—and they have not returned.” As quality of life decreased, patients became highly activated in their search for a solution to get better; their behaviors included information seeking and persistence regarding FMT pursuance. Participants spent a significant amount of time researching treatments, and thereby increased their confidence in directly asking their providers about FMT. As a result, patients were empowered to take ownership in their health and treatment options. Representative quotes for patient activation examples are presented in Table 2. Before FMT receipt, participants would reach a tipping point (Fig 1) at which the buildup of the burden of symptoms led to feelings of hopelessness about their options and their future. At this time, participants took initiative by seeking out FMT (ie, selfreferral) by contacting an FMT physician. Regarding the themes identified in the time period FMT, participants commented on how easy it was to undergo and the lack of a so-called ick factor, and that the stool donor faced the most anxiety. In the period postFMT, participants revealed that although there was a nearly immediate resolution of diarrhea, many experienced residual effects from having long-standing diarrhea, such as irritable bowel symptoms. Although physical symptoms were immediate, other effects took several months up to 1 year to resolve, including fears of recurrence. Other themes were the ability of the patient to resume daily activities and a display of gratitude toward the FMT-performing physician. Patient activation behaviors during these time periods included advocacy for FMT, accountability, and empowerment (Table 3). Representative quotes for identified themes from the tipping point, FMT, and post-FMT periods are presented in Table 3.
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Table 2 Examples of patient activation during fecal microbiota transplantation (FMT) periods Period
Activation type
Representative/supportive quotation(s)
Pre-FMT
Empowerment
Pre-FMT Pre-FMT
Information seeking Persistence
FMT Post-FMT Post-FMT
Empowerment Advocacy Accountability
“I called up my insurance company and yelled at them because they wouldn’t cover any of it [vancomycin].” “I had to fight with the doctor . . . they were going to put me back on [metronidazole] again, which is what I had been on the past 5 months.” “I had read up on it on the Internet and I basically knew there are 2 ways it was done, either through a colonoscopy or a nasal gastric tube. It made no difference to me how it was done I just wanted it done.” “I did a lot or research online and found that they were doing it [FMT] in countries like England and Australia, but I couldn’t find anyone here in the United States much less the East Coast. I just kept researching it for months. I don’t know if I typed in the right words or what, but all of a sudden [my doctor’s] name popped up. That was a Sunday and I called him first thing Monday morning.” “I said what do I have to lose. I can’t live like this . . . it’s an option [FMT] and I’m going for it.” “I want the whole world to know about the procedure, use my name, I would get on television and talk about it.” “I did go back to all these people who thought it [FMT] was a bogus thing . . . I went back face to face . . . I even called the director of the hospital. I said if this had not been done for my mother she probably wouldn’t be here because your physician didn’t do anything. I made sure when I left there they knew, because it could be somebody else who comes along and gets it as bad as she did.”
FMT, Fecal microbiota transplantation.
Table 3 Summary of themes identified during tipping point, fecal microbiota transplantation (FMT), and post-FMT periods Period
Themes
Tipping point
Hopelessness/frustration
FMT
Donor Easy/quick No ick factor Relief
Post-FMT
Residual symptoms Residual fear/caution
Resuming of daily activities
Gratitude toward physician performing FMT
Representative/supportive quotation(s) “I was out of options.” “So I was caught for about 5, 6 months in this spot where I was trying to decide whether to take vancomycin for the rest of my life, but life is not worth living with Clostridium difficile” “He [the donor] had performance anxiety.” “Abracadabra. It was you’ve got to be kidding me, is this all I had to do?” “But there is no smell, no taste, no after anything, there’s nothing to be afraid of or to be concerned about.” “I felt very, very, very shortly, like within a day or 2, I could feel that there was a difference in my body, my intestines weren’t tied up in a knot and screaming, and my body felt like it was actually going to survive.” “But to this day I still have—there are certain times where certain foods, if, I guess, they have a higher roughage or some level or something I’m not going to be happy. So I have to watch what I eat now.” “I won’t take antibiotics unless they are life or death. I will not.” “I still am very cautious about hygiene. I still have my husband using a different bathroom in the house than I am using.” “I had time to kind of say am I really better? You know, you’re very tentative, you’re afraid to make plans . . . all this weird mind game.” “It was like night and day because then I was off antibiotics and I felt like 100%. I was going back to the gym, back at work, absolutely no diarrhea at all.” “I was back to living, I was back to my friends, I was back to entertaining, we would go out to dinner with our friends and I wasn’t afraid, because with that C difficile there is a huge fear factor.” “I would stand on my head for him right now, as I think most of his patients would.” “He saved my life, because I have no doubt if I didn’t have the transplant I would be dead, because they had used every drug they could think of.”
Analysis of the closing interview question led to findings regarding anger toward the barriers that participants encountered, including those set by treating physicians and the Food and Drug Administration (in reference to a policy during a 2-month period in 2013 during which Investigational New Drug application approval was necessary by the FMT-treating physician).21 One participant stated, “I am angry that people were denied the opportunity to have it [FMT] done for them.” Frustration was evident from having residual symptoms and not having undergone FMT sooner, as expressed by 2 participants: “My hair was falling out . . . everybody who saw me said I looked horrible. I don’t understand why this isn’t offered sooner rather than later, because I think my recovery would have been quicker” and, “What I feel really sad about is that I wasn’t given this opportunity earlier in treatment . . . that my doctors out here in suburbia just thought they were going to medicate me forever.” The closing question also revealed several areas of participantoffered advice directed mainly toward FMT barriers, including that awareness should be increased regarding FMT as a treatment, of its effectiveness, and the need for more FMT providers. For example, regarding FMT as a treatment, 1 participant stated, “Maybe you let the vancomycin fail once and then use the [fidaxomicin], and then do the transplant, as opposed to [fidaxomicin] has to fail 3 times and then the other has to fail and finally, oh, we’ve got nothing else.” Another participant remarked, “Doctors need to understand that not everybody is going to be able to heal or get better from this infection
by [metronidazole] or vancomycin, you’ve got to think about the next plan of action.” Regarding FMT availability, 1 participant commented that “there’s not enough people doing these procedures.” DISCUSSION There were several insightful findings from participants’ experiences in undergoing FMT. In the time leading to FMT, participants experienced difficulty mentally, financially, and physically, and they needed to rely on support networks to carry out usual daily activities. Feelings of hopelessness about their condition and frustration stemming from encountering health system barriers to FMT led to a tipping point at which activated patients would initiate plans to undergo FMT. Immediate resolution of diarrhea was experienced; however, there were residual effects, such as fears concerning recurrence. During the post-FMT period, participants displayed further examples of patient activation, including willingness to serve as an FMT advocate to increase provider awareness, and taking measures to hold providers accountable. Participants advised that FMT should be offered sooner in the course of treatment, and that provider education is needed regarding FMT. Similar to our findings, previous reports of patient experiences relayed the physical aspects of C difficile infection,22 as well as feelings of depression and isolation, being worried about contagiousness, and the possibility of reinfection.18 We found that participants
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encountered multiple barriers to receiving FMT, including a lack of FMT providers, low awareness among physicians, and physician resistance. A survey administered to infectious diseases physicians about FMT showed that although the majority of those surveyed (80%) would consider FMT, logistical issues regarding fecal donor preparation and delivery and donor testing were commonplace.16 Another survey of physicians’ attitudes showed that among reasons cited for not offering FMT, 24% believed patients would find FMT unappealing, with 23% stating that institutional barriers were a problem, and 18% found FMT unappealing themselves.17 The majority of participants had to seek out FMT on their own initiative in our study. This aligns with findings by Zipursky et al,14 who found that among patients surveyed regarding their perceptions towards FMT, that although respondents deemed aspects of FMT unappealing, the majority selected it as a treatment for recurrence in hypothetical case scenarios. Among patients who have undergone FMT, it was reported that they had no concerns about any aspects of FMT.23 Patient activation behaviors, including information seeking, identifying treatment options, and having confidence to talk about treatment with providers,20,24 were commonly reported by participants. Our findings suggest that conditions such as C difficile infection that are quick-onset, debilitating, and that significantly influence daily activities and quality of life can rapidly motivate patients to take on activating behaviors. From the participant stories, patient activation behaviors appeared to increase as antibiotic treatment failed and patients were told they were out of options and thereby took to finding their own solution, including identification of the FMT provider, often through an Internet search conducted by the respondent or friend or family member, and self-referral to the FMT provider. The eagerness for which respondents embraced serving as advocates was also an interesting finding, driven, in part, by changes in FMT regulation by the Food and Drug Administration during the study period.21,25 Given that patient activation levels vary,20,24 it is important that all patients with recurrent C difficile infection are aware of options, including FMT, to make timely informed decisions about their condition. Although the respondents, on average, went 7.2 months between initial infection and FMT and multiple courses of pulsed/tapered vancomycin and or fidaxomicin, a guideline by the American College of Gastroenterology recommends FMT for a third recurrence after a pulsed vancomycin regimen.26 Further, as participants reported that they relied upon caregivers, mainly family members, to assist with day-to-day activities, caregiver support should be considered in the treatment plan. Those with low support may need assistance with transportation to appointments, delivery of medications, and arranging home delivery of groceries. This study has a few limitations. One is that the study sample represents relatively healthy participants who volunteered to undergo a telephone interview; the experiences may not necessarily represent those who are more severely ill, nor those who may have had a negative experience. Further, the results represent participant experiences in 1 FMT setting, and given the varying time spans between the undergoing of FMT and the interview among respondents, it is possible that respondent recall was influenced differentially by the amount of time that passed since undergoing FMT. Further, whereas thematic development through an inductive coding process was used to inform upon the experiences of respondents, it is possible that data saturation did not occur, meaning that the point where no new information was gathered with conduction of further interviews was reached.19 Finally, although depictions of the FMT experience were conveyed mostly by those who have undergone FMT, 2 of the interviews were carried out with family members who did not personally experience FMT.
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CONCLUSIONS Although activated patients may seek FMT for the treatment of C difficile infection recurrence and have resolution, the experiences of those undergoing FMT indicate the need for an effective treatment that can be delivered in a timely and consistent manner to avoid prolonged debilitating effects on physical and mental health. Although FMT effectiveness has been demonstrated with suggested indications for use and with few short-term adverse effects, and whereas FMT may be effective in decreasing C difficile contagiousness,12,26,27 participants frequently encountered barriers toward FMT and faced provider unawareness about FMT as a treatment option. Although there are promising treatments on the horizon, including synthetic stool substitute and C difficile nontoxigenic strain therapies,28,29 FMT currently remains the most viable option for resolution of recurrence, underscoring the need for increased consideration of and availability for FMT treatment.
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