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Fecal microbiota transplantation for treatment of Clostridioides difficile infection

Fecal microbiota transplantation for treatment of Clostridioides difficile infection
Authors:
Thomas J Borody, MD, PhD, FRACP, FACG, FACP, AGAF, DSc, FRSN
Sanjay Ramrakha, MBBS, PhD
Section Editor:
J Thomas Lamont, MD
Deputy Editors:
Milana Bogorodskaya, MD
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Feb 2022. | This topic last updated: Feb 15, 2022.

INTRODUCTION — Fecal microbiota transplantation (FMT) refers to instillation of processed stool collected from a healthy donor into the intestinal tract of a patient with Clostridioides difficile infection (CDI) [1-4]. FMT protocols vary between institutions, and comparative efficacy studies are few and underpowered.

Available data are strongest for use of FMT in the setting of recurrent CDI; recurrent CDI is defined by complete abatement of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms within two to eight weeks after treatment has been stopped [2]. Recurrent CDI occurs in 10 to 25 percent of patients treated with antimicrobial therapy.

Data on additional circumstances in which FMT may be beneficial, such as severe and fulminant infection, are limited.

Issues related to FMT are reviewed here. Other issues related to CDI are discussed separately. (See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology" and "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridioides difficile infection in adults: Treatment and prevention".) (Related Pathway(s): Clostridioides difficile infection: Treatment of adults with an initial or recurrent infection.)

RATIONALE — The gastrointestinal tract harbors a highly complex community of microorganisms that exist in symbiosis with the host. The human gut microbiota is estimated to consist of at least 1014 bacteria and as many as 1000 to 1200 bacterial species, most of which reside in the colon [5].

The beneficial roles mediated by the microbiota for the host include vitamin synthesis, fermentation of dietary carbohydrates, metabolism of bile and host hormones, and competitive exclusion ("colonization resistance") of pathogens taking residence in the gut community [6]. The microbiota also influences the development and maturation of the immune system through interactions with the gut epithelium [7,8].

Administration of antibiotics can significantly alter the composition of the microbiota, which can lead to selective removal of bacteria that serve as a barrier to pathogen colonization and/or persistence [9,10]. Antibiotic-mediated changes in the composition of the gut microbiota may also lead to homeostatic imbalance through alterations in the gut barrier functions and result in mucosal immune defects, which would predispose the host to enteric infections such as C. difficile by allowing environmentally acquired spores to germinate and successfully colonize the gut [11].

Recurrence of CDI is an increasing problem following antimicrobial therapy. Patients with recurrent CDI have been observed to have reduced diversity of the intestinal microbiome and diminished numbers of bacteria relative to healthy individuals [12,13]. Transplantation of stool microbiota from healthy individuals to patients with recurrent C. difficile can restore these missing strains and break the cycle of CDI recurrence [14-17].

SAFETY AND EFFICACY

Cure rates — The efficacy of FMT is discussed separately. (See "Clostridioides difficile infection in adults: Treatment and prevention".)

More than one administration of FMT may be necessary for optimal efficacy, and this is the reason we suggest at least two sequential administrations of FMT, as discussed below (see 'Administration protocol' below). In one randomized trial including 232 patients with recurrent CDI treated with fresh or frozen FMT administered via enema, patients with no improvement in symptoms by day 4 received an additional FMT between days 5 and 9; those who did not respond to two FMTs were offered repeat FMT or antibiotic therapy [18]. The efficacy for one FMT was approximately 50 percent and increased to 75 percent for two FMT administrations and approximately 90 percent for more than two FMT administrations. However, despite this, the US Food and Drug Administration (FDA) generally recommends only a single administration.

Alteration of the colonic microbiota following FMT appears to be durable [15,19,20]. In one retrospective study including 374 patients with risk factor exposure, 78 percent (95% CI 73-84) had durable response to FMT at one year [20]. Similarly, in an observational study including 137 patients who underwent FMT for recurrent CDI, durable cure at median 22 months follow-up was observed in 82 percent of patients; patients with recurrence had antibiotic exposure following FMT [19].

The efficacy of FMT in patients with underlying inflammatory bowel disease (IBD) is lower than in patients without IBD, and flares of underlying disease activity have been reported following FMT for recurrent CDI in patients with IBD [21-23]. The FMT efficacy rates differ by route of delivery. (See 'Choice of delivery route' below.)

Other effects — CDI has been associated with bloodstream infection (BSI). FMT may decrease the strength of that association. In a prospective cohort study of 290 patients with recurrent CDI, treatment with FMT was associated with a lower risk of subsequent BSI within 90 days compared with antibiotic therapy for CDI [24]. The FMT group also had fewer days of hospitalization and an increase in overall survival compared to the antibiotic group.

Adverse events and complications — In patients without underlying comorbidities, FMT is generally well-tolerated; mild to moderate adverse events (such as abdominal discomfort) are generally self-limited [19,25-30]. In one review including more than 1000 patients, the incidence of serious adverse events including death, infection, and relapse of inflammatory bowel disease was 3.5, 2.5, and 0.6 percent, respectively [27].

Potential risks include:

Procedural complications - Complications associated with the FMT procedure (upper gastrointestinal bleeding after nasogastric tube insertion, colon perforation during colonoscopy) have occurred; the frequency of such complications is likely similar to the frequency of complications when these procedures are performed for other indications [31]. (See 'Choice of delivery route' below and "Overview of colonoscopy in adults", section on 'Complications' and "Inpatient placement and management of nasogastric and nasoenteric tubes in adults", section on 'Complications'.)

Risk for transmission of infection - FMT is associated with risk for transmission of infectious agents:

In a surveillance report including more than 10,000 fecal microbiota preparations, adverse events occurred in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin–producing Escherichia coli; the organism went undetected despite screening [32].

In 2019, the FDA released a safety alert highlighting two cases (one fatal) of invasive infection due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli among FMT recipients [33,34]. One patient had profound neutropenia as a result of hematopoietic cell transplantation. No ESBL E. coli-related illness occurred in 16 other individuals who received the same contaminated capsules.

Cases of norovirus gastroenteritis have been attributed to FMT, despite use of asymptomatic donors with no known sick contacts [35].

Strategies to reduce transmission risk include careful selection of FMT candidates and adherence to guidelines for donor selection. (See 'Candidates for FMT' below and 'Stool donor selection' below.)

CLINICAL APPROACH

Candidates for FMT — For patients who have received appropriate antibiotic treatment for at least three CDI episodes (ie, initial episode plus two recurrences), who subsequently present with a fourth or further episode (third or subsequent recurrence), we favor FMT in regions where available [1,2]. However, some favor FMT for patients who have received antibiotic treatment for at least two CDI episodes (ie, initial episode plus one recurrence) [3]. (See "Clostridioides difficile infection in adults: Treatment and prevention".)

We avoid FMT in immunocompromised patients and patients with inflammatory bowel disease.

FMT may have a role in management of patients with severe or fulminant disease; this requires further study. (See "Clostridioides difficile infection in adults: Treatment and prevention", section on 'Fulminant colitis' and "Clostridioides difficile infection in adults: Treatment and prevention".)

Pretreatment evaluation

History and physical examination — The aim of the history is to guide selection of the route of delivery in patients who are candidates for FMT. (See 'Our approach' below.)

Patients should be evaluated to determine if they have a history of dysphagia or conditions that could prevent passage of FMT capsules or cause capsules to break open prematurely. Conditions that would preclude oral administration of FMT capsules include a known esophageal stricture, Zenker's diverticulum, gastroparesis, or a prior history of small bowel obstruction.

The history should also include prior surgeries including subtotal colectomy or colostomy, as FMT administration via colonoscopy may be associated with diminished efficacy due to reduced colonic mucosa area.

In addition, FMT recipients require assessment of their sedation needs and risks associated with endoscopy. (See "Overview of colonoscopy in adults", section on 'Sedation assessment'.)

Laboratory testing — There are no standard guidelines regarding the approach to recipient laboratory testing prior to FMT. We perform baseline serologic testing for viral hepatitis (A, B, and C), HIV, and syphilis; in addition, we perform stool culture for enteric pathogens and stool microscopy examination for ova and parasites, and we screen stool for multidrug-resistant organisms. Such screening is important to document presence of infection prior to FMT administration (which could serve as a potential source of disease transmission).

Some clinicians favor expanded laboratory testing for donor stool to include severe acute respiratory syndrome coronavirus 2 and drug-resistant bacteria [28,36]. However, the cost of expanded stool screening may limit FMT access [37].

Choice of delivery route

Delivery routes and efficacy — FMT may be administered via oral capsules, lower gastrointestinal (GI) tract procedure (colonoscopy, retention enema), or upper GI tract procedure (nasojejunal [NJ]/nasoduodenal [ND] tube) [38,39]. The choice is based in part on clinical circumstances, available options, and patient preference. There have been few trials comparing the effectiveness of different modalities; in one meta-analysis including 37 studies (of which 7 were randomized trials) and more than 51,000 patients, the mean response for FMT in recurrent CDI was 92 percent; lower administration was more effective than upper administration (92 to 97 percent versus 82 to 94 percent) [40].

Oral capsules – Administration of FMT via oral capsules is convenient and noninvasive [41,42]. In a meta-analysis that included 15 studies (most of which were observational) and more than 700 patients, 82 percent of patients treated with oral capsule-based FMT did not have recurrence during follow-up, which is similar to efficacy rates seen with colonoscopy-based FMT [43]. As an example of one of the randomized trials included in the meta-analysis, among 116 patients with recurrent CDI randomized to FMT administered via oral capsule or colonoscopy, cure rates for prevention of recurrent CDI were 96 percent in both groups at 12 weeks [44]. Rates of minor adverse events in the oral capsule and colonoscopy groups were 5 and 13 percent, respectively. Larger studies are needed to confirm these results and evaluate long-term effectiveness and safety.

Colonoscopy – Administration of FMT via colonoscopy allows delivery of donor stool to the cecum and distal small bowel. In addition, it permits inspection of the colon for presence of colitis, pseudomembranes, polyps, or cancer. However, colonoscopy carries some procedural risk and increases health care utilization and costs. Several studies have noted success with administration of FMT via colonoscopy [17,26,45,46]. Cure rates after lower GI tract administration are somewhat higher than cure rates after upper GI tract administration. In one retrospective study including 22 patients with recurrent CDI, patients treated with lower GI FMT recovered faster than patients treated with upper GI FMT (1.6 versus 2.4 days) and were more likely to achieve cure (100 versus 75 percent) [47,48].

Retention enema – Administration of donor stool via retention enema allows delivery of donor stool up to the splenic flexure. Retention enema is inexpensive and has low procedural risk. Self-administered home FMT via enema kit has also been performed successfully [49]. However, it may be difficult for some patients to retain the donor material and may therefore require multiple treatments.

While several studies have noted success with this approach, cure rates with enema appear to be lower than colonoscopy [49-53].

Nasojejunal/nasoduodenal tube – Administration of FMT via NJ/ND tube allows delivery of donor stool to the small bowel and then throughout the colon [25,54-59]. Placement of NJ/ND tube is uncomfortable and requires radiologic confirmation of tube placement. Administration via the upper GI tract also carries some risk of vomiting and aspiration.

In a randomized clinical trial evaluating FMT, 43 patients with recurrent CDI were randomized to receive treatment with oral vancomycin (500 mg orally four times per day for 14 days), oral vancomycin with bowel lavage, or a four-day course of vancomycin followed by bowel lavage and subsequent FMT administered via ND tube [25]. Cure rates were higher among those who received FMT than those who did not (81 versus 27 and 31 percent, respectively).

Cure rates after upper tract administration are somewhat lower than cure rates after lower tract administration [47,48]. Single FMT instillations via the upper GI tract have lower rates of success than via the lower GI tract, but success rates generally increase with repeated instillations [18,25,60,61].

Our approach — The choice of FMT delivery route depends in part on patient preferences, individual risk, availability of resources and expertise, and cost. (See 'History and physical examination' above.)

The American College of Gastroenterology 2021 guidelines favor administration of FMT via colonoscopy or oral capsules, with delivery by enema if other methods are unavailable [3]. If feasible, we administer FMT via oral capsules; in some areas, stool banks serve as a source of capsules prepared from screened donors [62]. If FMT administration via oral capsules is not feasible, we administer FMT via colonoscopy, followed by retention enema the following day. If FMT administration via oral capsule, colonoscopy, or retention enema is not feasible, we administer FMT via an endoscopically placed NJ (preferably) or ND tube.

In patients with history of subtotal colectomy or colostomy, transcolonic administration is more likely to fail. Administration via oral capsules or upper GI tract is preferred. If FMT administration via colonoscopy is pursued in such patients, we administer daily retention enemas for five days. (See 'Pretreatment evaluation' above.)

In patients with severe colitis or toxic megacolon, FMT administration via colonoscopy may not be feasible. In such patients, FMT is administered via NJ tube or by a gently performed rectal enema. For patients with severe CDI who would otherwise require colectomy, a promising alternative approach consists of loop colostomy followed by antegrade administration of FMT; further study is needed [63].

Administration protocol

Oral capsules — Stool banks serve as a source of capsules prepared from screened donors in some areas [62]. A large number of capsules (as many as 40) may be required [44]. Patients undergoing FMT via oral capsules should be managed according to the protocol of the capsule manufacturer.

Lower GI tract — There is no consensus on the optimal protocol for FMT administration via the lower GI tract; the following discussion reflects the clinical approach of the authors.

For patients with active colitis, we administer oral vancomycin (500 mg orally twice daily) for seven days prior to FMT; the last dose should be 24 hours before the procedure. In the absence of active colitis, we do not administer antibiotics prior to FMT, given some data suggesting this practice may be associated with diminished efficacy [64-67].

The day prior to the procedure, administer three to four liters of oral polyethylene glycol with electrolytes purgative. This lavage may reduce the density of vegetative C. difficile organisms, including the metabolically inactive spores that could otherwise convert to vegetative forms. We forego the lavage in patients too ill to tolerate it. (See "Bowel preparation before colonoscopy in adults", section on 'Polyethylene glycol-electrolyte lavage solution'.)

Patients should be kept fasting overnight. The day of the procedure, administer 200 to 300 g of donor stool suspended in 200 to 300 mL of sterile normal saline via colonoscopy into the cecum or terminal ileum, within 10 minutes of preparation. Colonoscopy must be performed with caution given increased risk of perforation in the setting of CDI. If feasible, the scope should be passed to the cecum to exclude other pathology. If this is unfeasible due to colonic inflammation, the infusion should be performed at the most proximal aspect of the colon reachable via colonoscopy.

Patients may resume a regular diet and medications two hours after the colonoscopy is complete.

The following day, FMT is administered via a retention enema (200 to 300 g of donor stool suspended in 200 to 300 mL of sterile normal saline). The enema should be retained for at least six hours if feasible. We pretreat with loperamide (2 mg, followed by an additional 2 mg every two hours, up to a total of 8 mg) to increase enema retention. Patients should be advised to retain the stool as long as possible.

In patients with CDI in the setting of inflammatory bowel disease or a history of a subtotal colectomy or colostomy, we administer daily retention enemas of stool for five days.

In our clinical experience, the outlined protocol for FMT administration via the lower GI tract has been effective in achieving prolonged cure in over 90 percent of patients after a single procedure (>98 percent after two procedures), with long-term resolution of symptoms (diarrhea, abdominal pain or cramping) [48,60,68]. Efficacy rates for FMT administration via the lower GI tract are discussed separately. (See 'Choice of delivery route' above.)

Upper GI tract — One protocol for upper GI tract FMT administration consists of the following steps:

For patients with active colitis, we administer oral vancomycin (500 mg orally twice daily) for seven days prior to FMT; the last dose should be 24 hours before the procedure. In the absence of active colitis, we do not administer antibiotics prior to FMT, given some data suggesting this practice may be associated with diminished efficacy [64-67].

Patients should be kept fasting overnight. The day prior to the procedure, some experts administer three to four liters of oral polyethylene glycol with electrolytes purgative; this lavage may reduce the density of vegetative C. difficile organisms, including the metabolically inactive spores that could otherwise convert to vegetative forms. However, it is reasonable to forgo the lavage in patients too ill to tolerate it. (See "Bowel preparation before colonoscopy in adults", section on 'Polyethylene glycol-electrolyte lavage solution'.)

The evening prior to the procedure and the day of the procedure, administer a proton pump inhibitor (eg, omeprazole 20 mg). The rationale is to reduce the gastric acid barrier and enhance successful passage of live bacteria through the gastric mucosa.

The day of the procedure, place a NJ (preferred) or ND tube through the nostril and advance into the small bowel. Tube position is confirmed by radiograph and gastrografin follow-through. Use of sedation with ND instillation minimally increases the potential risk of aspiration; we forgo sedation if feasible [69].

We administer metoclopramide (10 mg intravenously), approximately 15 to 30 minutes prior to instillation of stool. Diluted stool (25 to 30 g of stool diluted in 50 mL of saline) is subsequently administered slowly, over 5 to 10 minutes, via NJ or ND tube.

Patients may benefit from repeat FMT administered daily over multiple days, given the lower efficacy of single administration via the upper GI tract as compared with colonoscopy. The total number is based on the response to treatment. (See 'Delivery routes and efficacy' above.)

Monitoring and disposition — FMT administered via oral capsules, ND/NJ tube, or retention enema can be performed in the outpatient setting. Following colonoscopy, hospitalization is not routinely recommended. However, some patients may require hospital admission; this decision should be tailored to individual patient circumstances.

Patients with nonsevere CDI treated with FMT typically have resolution of abdominal discomfort and diarrhea in 36 to 48 hours [18,25,29,48,59,70,71]. In one survey including 137 patients treated with FMT for recurrent CDI, durable response (no recurrence of CDI at 22 months of follow-up) was observed in 82 percent of patients [19].

FMT PREPARATION

Stool donor selection — Stool donors must be rigorously screened through questionnaires as well as blood and stool testing. Donors must be healthy and have a daily formed bowel movement. Exclusion criteria are summarized in the table (table 1) [28].

Careful evaluation of candidate stool donors for occult pathogens is important to minimize the risk of infection and to maximize the likelihood for a successful treatment outcome.

If feasible, FMT should be performed with stool screened by a stool bank. If prescreened donor stool is not available, our approach to screening includes the following tests:

Serologic testing for viral hepatitis (A, B, and C), HIV, and syphilis

Stool tests should include:

Giardia antigen, Cryptosporidium antigen

Microscopy examination for ova and parasites and acid-fast stain microscopy (for Cyclospora, Isospora, Dientamoeba fragilis, and Blastocystis hominis)

Molecular tests for norovirus and rotavirus

Bacterial culture for detection of enteric bacterial pathogens, as well as testing for multidrug-resistant enteric organisms

Nucleic acid amplification tests for enteropathogenic E. coli and Shigatoxin-producing E. coli [72]

C. difficile to rule out asymptomatic carriage, even if stool is formed

Helicobacter pylori stool antigen assay (for FMT to be administered via upper gastrointestinal [GI] tract)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; for stool donated after December 1, 2019) [73]. In March 2020, the US Food and Drug Administration advised that for stool donated after December 1, 2019, the donor and the samples should be screened for SARS-CoV-2 (the virus that causes coronavirus disease 2019), since this virus can be detected in stool and thus theoretically could transmit virus [73,74].

FMT products

Stool-based products — In general, FMT protocols utilize donor stool suspended in normal saline prior to administration (via colonoscopy, enema, or nasoduodenal/nasojejunal tube). Stool is homogenized (using blender, manual effort, or other method) to liquid consistency and filtered (eg, gauze, coffee filter, strainer) to remove particulate matter. This processed specimen is then either directly infused into the GI tract or further centrifuged and capsulized in gelatin capsules that can be administered orally. (See 'Choice of delivery route' above and 'Oral capsules' above.)

Stool banks serve as a source of capsules prepared from screened donors in some areas [62].

Use of frozen stool preparations for FMT has been shown to be noninferior to fresh stool preparations and allows the use of stool banks for distribution of FMT [18,75]. In one randomized trial including 219 patients with recurrent CDI randomized to receive frozen or fresh FMT via rectal enema, the rates of clinical resolution were comparable (75 versus 70 percent) [18].

Specific bacterial FMT — Specific bacterial stool substitutes for FMT are under investigation for the treatment and prevention of recurrence of CDI [76,77]. In a phase III trial, 182 patients with recurrent (three or more episodes) CDI who had resolution of symptoms after treatment with standard-of-care antibiotics were assigned an oral capsule composed of live purified Firmicutes spores (SER-109) or placebo. Administration of SER-109 significantly decreased recurrence rates relative to placebo (12 versus 40 percent) up to eight weeks after treatment [76].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Clostridioides difficile infection".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Antibiotic-associated diarrhea (C. difficile infection) (The Basics)")

Beyond the Basics topic (see "Patient education: Antibiotic-associated diarrhea caused by Clostridioides difficile (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Fecal microbiota transplantation (FMT; instillation of processed stool collected from a healthy donor into the intestinal tract of a patient with recurrent Clostridioides difficile infection [CDI]) is effective for treatment of recurrent CDI. FMT is a relatively new therapy; protocols vary between institutions, and comparative efficacy studies are few and underpowered. (See 'Introduction' above.)

Patients with recurrent CDI have been observed to have reduced diversity of the intestinal microbiome and diminished numbers of bacteria relative to healthy individuals. Transplantation of stool microbiota from healthy individuals to patients with recurrent C. difficile can restore these missing strains and break the cycle of CDI recurrence. (See 'Rationale' above.)

For patients who have received appropriate antibiotic treatment for at least three CDI episodes (ie, initial episode plus two recurrences), who subsequently present with a fourth or further episode (third or subsequent recurrence), we suggest FMT in settings where expertise is available (Grade 2B). (See 'Cure rates' above and "Clostridioides difficile infection in adults: Treatment and prevention".)

FMT may be administered via oral capsules, lower gastrointestinal (GI) tract procedure (colonoscopy, retention enema), or upper GI tract procedure (nasojejunal [NJ]/nasoduodenal [ND] tube). The optimal approach to FMT administration is uncertain. The pretreatment evaluation can guide selection of the route of delivery in patients who are candidates for FMT. (See 'Pretreatment evaluation' above and 'Choice of delivery route' above.)

The choice of delivery route depends in part on patient preferences, individual risk, availability of resources and expertise, and cost. If feasible, we administer FMT via oral capsules. If FMT administration via oral capsules is not feasible, we administer FMT via colonoscopy followed by a retention enema the following day. We reserve FMT administration via NJ or ND tube for patients who cannot undergo FMT via an alternate route. (See 'Our approach' above.)

Patients with nonsevere CDI treated with FMT typically have resolution of abdominal discomfort and diarrhea in 36 to 48 hours. (See 'Monitoring and disposition' above.)

Rigorous screening of candidate stool donors for occult pathogens is important to minimize the risk of infection. Stool donors must be healthy and have a daily bowel movement. Exclusion criteria are summarized in the table (table 1). (See 'Stool donor selection' above.)

Stool is homogenized to liquid consistency and filtered to remove particulate matter. This specimen is then infused into the GI tract or further centrifuged and capsulized in gelatin capsules that can be administered orally. (See 'FMT products' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Sharyn Leis, RN, Gerald Pang, PhD, and Antony Wettstein, MBBS (Hons), who contributed to an earlier version of this topic review.

We are saddened by the death of Paul Rutgeerts, MD, who passed away in September 2020. UpToDate gratefully acknowledges Dr. Rutgeerts' work as our Section Editor for Gastroenterology.

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  45. Yoon SS, Brandt LJ. Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients. J Clin Gastroenterol 2010; 44:562.
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  48. Cammarota G, Masucci L, Ianiro G, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther 2015; 41:835.
  49. Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol 2010; 8:471.
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Topic 2604 Version 51.0

References

1 : Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults.

2 : Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA).

3 : ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections.

4 : The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

5 : A human gut microbial gene catalogue established by metagenomic sequencing.

6 : From structure to function: the ecology of host-associated microbial communities.

7 : Has the microbiota played a critical role in the evolution of the adaptive immune system?

8 : Molecular modulation of intestinal epithelial barrier: contribution of microbiota.

9 : Long-term ecological impacts of antibiotic administration on the human intestinal microbiota.

10 : Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation.

11 : Microbiota restoration: natural and supplemented recovery of human microbial communities.

12 : Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients.

13 : Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea.

14 : Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea.

15 : Durable alteration of the colonic microbiota by the administration of donor fecal flora.

16 : Fecal bacteriotherapy, fecal transplant, and the microbiome.

17 : Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology.

18 : Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

19 : Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection.

20 : Durability of Response to Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence in Patients With Clostridioides difficile Infection.

21 : Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection.

22 : Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.

23 : Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.

24 : Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.

25 : Duodenal infusion of donor feces for recurrent Clostridium difficile.

26 : Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial.

27 : Systematic Review: Adverse Events of Fecal Microbiota Transplantation.

28 : Treating Clostridium difficile infection with fecal microbiota transplantation.

29 : Fecal microbiome transplantation for recurrent Clostridium difficile infection: report on a case series.

30 : Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients.

31 : Post-Colonoscopy Complications: A Systematic Review, Time Trends, and Meta-Analysis of Population-Based Studies.

32 : Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.

33 : Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.

34 : Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant.

35 : Norovirus gastroenteritis after fecal microbiota transplantation for treatment of Clostridium difficile infection despite asymptomatic donors and lack of sick contacts.

36 : A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.

37 : Treatment approaches including fecal microbiota transplantation for recurrent Clostridium difficile infection (RCDI) among infectious disease physicians.

38 : Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis.

39 : Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review.

40 : Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.

41 : Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection.

42 : Effectiveness of fecal-derived microbiota transfer using orally administered capsules for recurrent Clostridium difficile infection.

43 : Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

44 : Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

45 : Treatment of refractory/recurrent C. difficile-associated disease by donated stool transplanted via colonoscopy: a case series of 12 patients.

46 : Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results.

47 : A Retrospective Comparison of Fecal Microbial Transplantation Methods for Recurrent Clostridium Difficile Infection.

48 : Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection.

49 : Success of self-administered home fecal transplantation for chronic Clostridium difficile infection.

50 : Management of Severe and Severe/Complicated Clostridoides difficile Infection Using Sequential Fecal Microbiota Transplant by Retention Enema.

51 : Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy.

52 : Fecal transplant via retention enema for refractory or recurrent Clostridium difficile infection.

53 : Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis.

54 : Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study.

55 : Faecal transplant for recurrent Clostridium difficile-associated diarrhoea: a UK case series.

56 : [Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces].

57 : Fecal bacteriotherapy for relapsing Clostridium difficile infection in a child: a proposed treatment protocol.

58 : Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection.

59 : Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube.

60 : Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection: description of a protocol with high success rate.

61 : Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study.

62 : Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study.

63 : An institutional comparison of total abdominal colectomy and diverting loop ileostomy and colonic lavage in the treatment of severe, complicated Clostridium difficile infections.

64 : Faecal Microbiota Transplantation is Effective for the Initial Treatment of Clostridium difficile Infection: A Retrospective Clinical Review.

65 : Treatment of First-TimeClostridium difficileInfection With Fecal Microbiota Transplantation

66 : Fecal Microbiota Transplantation for Primary Clostridium difficile Infection.

67 : Efficacy of Routine Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection: A Retrospective Cohort Study.

68 : Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review.

69 : Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection.

70 : Successful therapy of Clostridium difficile infection with fecal microbiota transplantation.

71 : Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

72 : Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

73 : Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review.

74 : Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.

75 : Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection.

76 : SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection.

77 : Stool substitute transplant therapy for the eradication of Clostridium difficile infection: 'RePOOPulating' the gut.