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

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2023. | This topic last updated: May 18, 2023.

INTRODUCTION

Fecal microbiota transplantation (FMT) refers to instillation of processed stool bacteria

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 CDI, are limited and are discussed elsewhere. (See "Clostridioides difficile
infection in adults: Treatment and prevention".)

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 'Adverse events'
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".)

Although FMT is not contraindicated in these patient populations, we proceed

cautiously with FMT in immunocompromised patients and patients with inflammatory
bowel disease due to their increased susceptibility to infection.

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 obtained via a
stool bank is inexpensive and has low procedural risk. Other options include a
commercially available fecal microbiota rectal suspension or a self-administered
home FMT via enema kit [49,50]. (See 'Stool-based products' below.)

While several studies have noted success with this approach, cure rates with
enema appear to be lower than colonoscopy [49,51-54].

● Nasojejunal/nasoduodenal tube – Administration of FMT via NJ/ND tube allows

delivery of donor stool to the small bowel and then throughout the colon [25,55-
60]. 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 [18,25,61,62].

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 [63]. 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 [64].

Administration protocol
Oral capsules — Stool banks serve as a source of capsules prepared from screened
donors in some areas [63]. A large number of capsules (as many as 40) may be
required [44]. A commercially-available oral capsule composed of live purified
Firmicutes spores is also available. (See 'Specific bacterial FMT' below.) 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 [65-68].

● 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 solutions'.)

● 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) [48,61,69]. 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 [65-68].

● 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 solutions'.)
 ● 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 [70].

● 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 [18,25,29,48,60,71,72]. 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 [73]

• 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) [74]. In March 2020, the US Food and Drug
Administration (FDA) 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 [74,75].

The clinical use of FMT has the potential to transmit monkeypox virus. On August 22,
2022, the FDA issued guidance to reduce the risk of transmission of monkeypox virus
[76]. Measures recommended by the FDA include screening donors, with questions
directed at identifying those at high risk for and those with recent or active mpox
(previously referred to as monkeypox) virus infection, and the development of
exclusion criteria to exclude donors with a positive questionnaire screen. Donor
screening should be performed retrospectively on FMT prepared from donor stool
collected on or after March 15, 2022. The FDA also recommends that all FMT
recipients undergo informed consent regarding the possible risk of transmitting
monkeypox virus via FMT. This recommendation is based on the presence of
monkeypox virus DNA in rectal swabs and/or stool samples from infected individuals,
including those without symptoms of mpox disease [77]. (See "Epidemiology, clinical
manifestations, and diagnosis of mpox (monkeypox)", section on 'Transmission'.)

FMT products

Stool-based products

● Stool FMT – 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. Stool FMT is available via a stool bank.
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
[18,78]. 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].
 ● Fecal microbiota rectal suspension – A commercial fecal microbiota rectal
suspension (Rebyota) has been approved by the US Food and Drug
Administration to prevent recurrence in patients with ≥2 episodes (first
recurrence) of CDI [50,79]. The rectal suspension is a live biotherapeutic product
that consists of numerous microbes (including Bacteroides spp) manufactured
from human stool. However, it is not widely available yet, and we await more data
comparing it to other sources of FMT and bezlotoxumab before adopting its use.

The enema is administered as a one-time dose of 150 mL via the rectum. It

should be administered 24 to 72 hours after the last dose of antibiotics for CDI
treatment. Prior to being given, the enema needs to be thawed in the refrigerator
for approximately 24 hours. Adverse effects are similar to those of any retention
enema and include mild abdominal pain, distension, diarrhea, flatulence, and
nausea.

In a double-blinded randomized controlled trial of 267 adults with ≥1 recurrent

treated CDI, those who received the stool-based rectal enema were more likely to
be recurrence-free at eight-week follow-up (71 versus 58 percent) [80]. More than
90 percent of those who were recurrence-free at eight weeks remained so by six
months of follow-up. Another randomized trial of adults with ≥2 CDI recurrences
that administered two doses of the rectal enema one week apart showed similar
results [81].

Specific bacterial FMT — A commercial fecal microbiota oral capsule (SER-109;

Vowst) has been approved by the US Food and Drug Administration to prevent
recurrence in patients with ≥2 episodes (first recurrence) of CDI [82]. The oral capsules
are composed of live purified Firmicutes spores. However, it is not widely available
yet, and we await more data comparing it to other sources of FMT and bezlotoxumab
before adopting its use.

The oral capsules are administered as four capsules once daily on an empty stomach
for three consecutive days. It should be administered two to four days after the last
dose of antibiotics for CDI treatment. Adverse effects are generally mild and include
mild abdominal distention, fatigue, constipation, chills, and diarrhea.
The oral capsules have shown to reduce the risk of recurrence of CDI in adults. As an
example, 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 [83]. Administration of SER-109 significantly decreased recurrence rates
relative to placebo (21 versus 47 percent) up to 24 weeks after treatment [84].

Other specific bacterial stool substitutes are undergoing investigation [85].

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: 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

● General – 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.)

● Rationale – 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.)

● Cure rates – 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".)

● Clinical approach

• 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.)

● Monitoring and disposition – 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.)

● Stool donor selection – 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.)

● FMT products – FMT products include donor stool suspended in normal saline,
commercially available rectal suspension of bacteria extracted from stool, or
commercially available oral capsules composed of live purified Firmicutes spores.
Other specific bacterial stool substitutes for FMT are undergoing investigation.
(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.

The UpToDate editorial staff acknowledges Paul Rutgeerts, MD (deceased), who

contributed to earlier versions of this topic review.
REFERENCES

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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. Clin Infect Dis 2021;
73:e1029.
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