Transcript Clostridium difficile

C.Difficile
an epidemic that is waiting for answers
Michael Gavin MD
Division of Gastroenterology
University of New Mexico
Burden of Clostridium difficile Infection
in the United States
n engl j med 372;9 nejm.org february 26, 2015
• C. difficile - almost half a million infections/yr
• Approximately 29,000 deaths in 2011
(within 30 days of infection)
• Persons 65 years of age or older, whites & females
had higher incidences than their comparators.
C. Difficile Infection in the Elderly
Keller JM Clinics in Geriatric Medicine 2014, 30:79-83.
• 92% deaths (C. Dif) occurred in age 65 & older
• Age itself is a risk factor
-after age 65, risk increases 2% a year
• 50% of residents of long-term facilities are
*asymptomatic carriers
*(20% of hospitalized pts.)
C. Difficile Infection in the Elderly
Keller JM Clinics in Geriatric Medicine 2014, 30:79-83.
Increase ratesSevere Disease
Medical complications
Mortality
Burden of Clostridium difficile Infection
in the United States
n engl j med 372;9 nejm.org february 26, 2015
• 24% of cases occurred inhospital settings,
(107,600 hospital-onset infections nationally)
• Of community-associated CDI, 82% estimated to be
associated with outpatient health care exposure.
• The rate of asymptomatic colonization in
nonhospitalized adults is to be 2%, with a higher
rate, up to 26%, in those with health care exposures.
Burden of Clostridium difficile Infection
in the United States
n engl j med 372;9 nejm.org february 26, 2015
• At least one recurrence of C. difficile infection
occurred in approximately 21% of cases of health
care–associated infection
• 14% of cases of community-associated infection
• Est. burden of 83,000 first recurrent infections
* repeated stool testing between 14 & 56 days after the initial C. difficile episode
Burden of Clostridium difficile Infection
in the United States
n engl j med 372;9 nejm.org february 26, 2015
• Counties under Surveillance: (10 Nationally)
New Mexico Bernalillo: 661,779 (population):
Community-Associated CDI Cases: 354
Incidence per 100,000 Persons:
53.4 (All sites: 48.2)
Health Care–Associated CDI Cases:
Incidence per 100,000 Persons:
727
109.9 (All sites: 92.8)
Burden of Clostridium difficile Infection
in the United States
n engl j med 372;9 nejm.org february 26, 2015
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NAP1 (PCR ribotypes 027): Binary toxin
NAP4 (PCR ribotypes 020):
NAP11(PCR ribotype 106):
* The NAP1 strain was more common among health care–associated cases than
among community-associated cases (30.7% vs. 18.8%, P<0.001)
Pathogenesis
 Fecal-oral route (20% of hospitalized pts.
colonized/hands of healthcare workers)
 Ingested: vegetative form or spores (resistant
to gastric acid)
 Spores germinate in small intestine
 Colonization (colon)- microbiome disrupted by
antibiotic therapy
Virulence factors
 Toxin A (TcdA) & Toxin (TcdB): exotoxins- bind human
intestinal epithelial cells
 Tcd A- enterotoxin
 (+)IL-6, IL-8 (epithelial cells), plus IL-1, TNF-A (monocytes)
 Tcd B- cytotoxin
 cell retraction and apoptosis (grossly visible as cell
rounding in tissue culture assays and as shallow ulceration
on the intestine mucosal surface)
• Majority disease attributable to both toxins
– 7-10% B toxin only
• Binary toxin: different toxin and hypervirulent strains
Pseudomembranous Colitis
Histopathology
 Type 1 PMC: mildest form (inflammatory changes
confined to the superficial epithelium) Typical
pseudomembranes are present
 Type 2 PMC: severe disruption of glands, marked
mucin secretion, more intense inflammation of basal
lamina
 Type 3 PMC: severe, intense necrosis of the full
thickness of the mucosa with a confluent
pseudomembrane
Pseudomembranes
B1/NAP1/027*
 Name
 B1: by its pulsed-field gel electrophoresis (PFGE) patttern
 NAP1: North American PFGE type 1 pattern
 027: PCR ribotype designation (Europe)
 Binary toxin*- similar to iota toxin of C.perfringens
 Produces higher levels of TcdA & TcdB
-due to truncated tcdC gene (negative regulator)
 Resistant to fluoroquinolones
* first reported in Canada (2004)
* an enzymatic & a binding component
Ananthakrishnan NR: Gastroenterology & Hepatology 8:17-25
Antibiotics
 Prior Exposure Antibiotics: 85% pts with
CDI within 28 days
 Antibiotic Utilization: Increased duration &
multiple antibiotics
– Clindamycin (1970-1980)
– Parenteral Cephalosporins (1980-1990’s)
– Fluoroquinolones (2000’s): inpts & outpts
PPI- risk factor for CDI
• 70% increased risk for CDI
• Independent risk factor for CDI in ICU pts.
• FDA (2/2012): “may predispose to CDI”
Dickinson B Surawicz Curr Gastroenterol Rep (2014) 16:399
Commercially available tests
• EIA against toxins (A&B)
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Detect both toxins
Greater sensitivity
False negatives high
Hence the classic thought of multiple tests
• GDH (glutamase dehydrogenase)
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Common antigen
High sensitivity
Low specificity
Can rule-out C. difficile
• PCR: new test with sensitivity and specificity
Toxin testing (Tricore)
 EIA-GDH (glutamate dehydrogenase)
-C. Difficile “common antigen”
plus
 EIA-toxin A/B
 If both tests (-), C. Difficile negative.
 If both tests (+), C. Difficile positive.
*Discordant results are reflexed to PCR assay.
Turn around time: 4-5 hrs.
Testing (Tricore)
Discordant results are reflexed to PCR assay:
 PCR toxin B gene:
 If PCR positive, C.Difficile is present.
 If PCR negative, C.Difficile is negative.
*Testing only on diarrheal stools (exception: Ileusrectal swap)
*Resubmissions after 7-day period
Diagnosis
• Stool tests:
– Identification of C. diff toxins A and/or B (Sensitivity 94100%; Specificity 99%)
– EIA (Sensitivity 60-95%; Specificity 99%)
– PCR (Sensitivity 94%; Specificity 97%)
Diagnosis: Treat the Pt. Not the Test
Polage CRJAMA Intern Med. doi:10.1001/jamainternmed.2015.4114
• (50%) (+) PCR results for C difficile do not experience adverse
events without treatment (asymptomatic colonization)
• 2-step testing with a screening test, such as glutamate
dehydrogenase antigen detection, followed by a toxin test to
confirm active infection is a reasonable diagnostic strategy.
Clinical Features
• Diarrhea (mild disease)
watery diarrhea with “manure” odor
• Diarrhea with colitis — watery diarrhea up to 10 or
15 times daily with lower abdominal pain and
cramping, low grade fever, and leukocytosis, lactic
acid elevation
*Inpatients with unexplained leukocytosis or fever consider CDI
(20% of patients with severe CDI have ileus)
Stages of Disease
 C. difficile Diarrhea: mild-mod. diarrhea , (-)
blood, (+)C.Dif toxin
 C. Difficile Colitis: high-volume watery diarrhea ,
fever, malaise, Leukocytosis, Flex Sigm:
erythematous , patchy mucosa
 Pseudomembranous Colitis (PMC): systemic
illness (yellow raised plagues ranging from 2-10
mm in diameter)
 Fulminant Colitis (paralytic ileus- toxic
megacolon- colonic perforation)
-dilated colon with severe toxicity
SHEA-IDSA Guideline
Clinical Case Defination
• Initial Episode:
Mild or Moderate
 Initial Episode:
Severe
 Initial Episode:
Severe, complicated
Laboratory Data and Clinical
Findings
• WBC < 15 K
• Serum Creatinine< 1.5X
pt’s premorbid baseline
 WBC >15K
• Serum creatinine>1.5x
pt’s premorbid baseline
• Hypotension, shock, ileus,
megacolon
SHEA-IDSA Guideline
Initial Episode
 Mild or Moderate:
 Severe:
 Severe, complicated
Treatment
 Metronidazole 500mg po
tid
(10-14 days)
 Vancomycin 125 mg po qid
(10-14 days)
 Vancomycin 500mg po qid
*Metronidazole 500mg IV q 8 hrs,
For Ileus, rectal vancomycin 500mg
qid (mixed in 100 cc NS)
Consider surgical consultation
Clinical Case Definition
Recommended Treatment
First recurrence:
Same as initial episode,
based on severity
 Second Recurrence:
Infectious Disease Consult
recommended
Do not use metronidazole beyond
first recurrence due
to risk of neurotoxicity.
 Vancomycin taper:
125 mg po qid 10-14 days
then
125 mg po bid 7days
then
125 mg po qd 7 days
then
125 mg po qod 2-8 weeks
Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile
McFarland L Elmer G Surawicz C ACG (2002) 97, 1769–1775
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choice of antibiotic treatments was limited to either low dose or high dose vancomycin
(500 or 2 g/day for 10 days) or metronidazole (1 g/day for 10 days). If the patient failed
the initial study's antibiotic treatment, the patient was considered a treatment failure
and the choice of the subsequent therapy was decided by the patient's physician.
Subsequent antibiotic treatments chosen by physicians included repeated 10- to 16-day
courses of an antibiotic; a "tapered regimen" (dose of vancomycin or metronidazole
started at one dose [500 mg to 3 g/day] and then decreased stepwise over a period of
time to doses ranging from 125 to 750 mg/day); a "pulsed regimen," which may or may
not have followed a 10- to 14-day course of vancomycin, followed by a pulse of a dose
of vancomycin (125–500 mg) every 2–3 days over a period of time (usually 3 wk); and a
combination of the above.
• Vancomycin was significantly more effective in clearing C. difficile culture
and/or toxin by the end of therapy than metronidazole (89% vs 59%,
respectively; p < 0.001).
Recurrent or relapsing CDI
Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium
difficile infections. Am J Gastroenterol 2013;108:478–498.
• At least three episodes of mild-to-moderate
CDI and failure of a 6- to 8-week taper with
vancomycin with or without an alternative
antibiotic (e.g., fidaxomicin, rifaximin) or at
least two episodes of severe CDI resulting in
hospitalization and associated with significant
morbidity.
Refractory CDI
Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium
difficile infections. Am J Gastroenterol 2013;108:478–498.
• Moderate CDI not responding to standard
therapy (vancomycin) for at least a week.
Severe CDI
Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium
difficile infections. Am J Gastroenterol 2013;108:478–498.
• White blood cells ≥15,000 cells/mm3, albumin
<3g/dl, and abdominal tenderness.
Complicated CDI
Surawicz CM, Brandt LJ, Binion DG et al. Guidelines for diagnosis, treatment, and prevention of Clostridium
difficile infections. Am J Gastroenterol 2013;108:478–498.
defined by at least one of the following:
• Admission to the intensive care unit
• hypotension with or without the use of vasopressors
• fever ≥38.5 °C
• ileus or significant abdominal distention, mental
status changes
• white blood cells ≥35,000 cells/mm3, or serum
lactate >2.2 mmol/l, or any evidence of end-organ
failure.
Metronidazole
First line Therapy
 (+)Inexpensive
 (+)Less risk of selecting vancomycin-resistant enterococci
 (-) absorbed rapidly (6-15% drug excreted in stool) and
decreases after treatment of CDI is initiated.
 (-) peripheral neuropathy, nausea, headache, dysgeusia
 Disease severity:
Vancomycin superior to Metronidazole in severe disease.
Zar, FA et al Clin. Infect. Dis.2007 45:302-307
Vancomycin
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(+)FDA –approved for CDI
(+)High fecal concentrations throughout treatment
(+)Lack of systemic toxicity
(-)Expensive (* compounded form: IV to elixir form)
(-) Bacterostatic
(-)20-30% recurrence of illness within 60 days
(occurs with metronidazole or vancomycin)
Fidaxomicin (DIFICID)
FDA–approved for CDI
• Macrolide antibacterial drug: 200mg bid X 10 days.
• Spectrum of activity: primarily against clostridia
species
• 92% recovered in stool
• Bactericidal
• Adverse reactions:
Nausea (11%), Vomiting (7%), Abdominal pain (6%)
(similar to vancomycin adverse reaction profile)
*Neutropenia (2%)
Fidaxomicin versus Vancomycin for Clostridium Difficile
N Engl J Med 2011;364:422-31
 (629) Adults(CDI): FID 200mg bid vs VAN 125mg qid
10 days
 Primary End point: Clinical cure- FID: 88% vs VAN: 86%
 Secondary End point:
Recurrence (4 weeks): FID: 15% vs VAN: 25% (p=0.005)
Clinical cure: resolution of diarrhea (ie 3 or fewer unformed stools for 2 days)
as of the second day after the end of treatment
Fidaxomicin versus Vancomycin for Clostridium Difficile
N Engl J Med 2011;364:422-31
 Bi/NAP1/027 strain : 35.9% of patients
Rates of Recurrence : FID: 24.4% vs. VAN: 23.6%
 Subgroup analysis: No significant difference
Severity of Disease
Patient’s age
Recurrent CDI
Fecal Microbiota Transplant
Recurrent/Refractory CDI (RCDI)
 Antibiotic-associated diarrhea (CDI?) 1958
-4 pts treated with human fecal enemas (cure: 4/4)
Eiseman Surgery 1958;444:854-859
 Recurrent CDI (1980’s): (6 pts)
-Human fecal enemas or bacterial mixture enema
-Bacteroides spp. absent during course of illness, restored!
Tvede et al Lancet 1,1156-1160 (1989)
Fecal Microbiota Transplant
 Nasogastrically Administered: 11 of 15 pts cured
(30 ml of “faecal fluid” via NGT- 30grms stool/150 ml nl saline)
Macconnachie AA et al QJ Med 2009; 102:781-784
 Nasogastrically Administered: 15 of 16 pts cured after 5 days of vancomycin
then bowel lavage and administration of fecal fluid through a nasoduodenal tube
compared to 4/13 with standard treatment with vancomycin and 3/13 with
vancomycin treatment and bowel lavage
van Nood E N Engl J Med. 2013 Jan 31;368(5):407-15
 Retention Enema: 7 of 7 pts cured
(50 ml of stool in 200 ml nl saline- given via enema bag.)
Silverman MS et al Clin Gastroenterol. Hepatol. 8,471-473 (2010)
Fecal Microbiota Transplant
Colonoscopy
 12 of 12 pts. with RCDI cured:
-400 cc injected from distal TI to rectum
Yoon SS & Brandt, LJ J. Clin Gastroenterol. 44,562-566(2010)
 18 of 19 pts with RCDI cured:
Rohlke F, Surawicz J Clin Gastroenterol. 44, 567-570 (2010)
 25 of 26 pts. with RCDI cured:
Kelly, C J Clin Gastroenterol. Feb;46(2):145-9 (2012)
Screening and Selection
• Patient Selection
– A. Adult patients following a third or further recurrence of C. difficile
colitis who have failed standard therapy with oral metronidazole
and/or oral vancomycin.
– B. Patient may not be severely immunocompromised: (advanced
HIV/AIDs, receiving chemotherapy or anti-TNF agents)
• Patient Screening: (document status prior to stool transfer)
– 1. HIV 1 & 2
– 2. Hepatitis A total, Hepatitis B surface antigen, surface antibody
and core antibody and Hepatitis C antibody
– 3. RPR (syphilis)
FMT for Treatment of Clostridium difficile Infection in
Immunocompromised Patients
Kelly CR. Am J Gastroenterol. 2014;doi:10.1038/ajg.2014.133.
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80 (IC) pts:(mean age of 75 adults- 53 yrs):
recurrent (55%), severe or complicated (34%) or refractory (11%) (CDI)
• 78% pts. resolved of CDI, with no recurrence at least 12 weeks
A second FMT was required in 12 pts. (8 were CDI free, resulting in an
overall CDI cure rate of 89%).
• In the IBD subset (n=36), CDI cure rate was 86% after a single FMT, and
94% overall.
-5 (14% of IBD patients) experienced disease flare post FMT.
-3(UC) pts had colectomy related to course of UC >100 days FMT
*SAE: Two deaths occurred within 12 weeks of FMT, one of which was the result of
aspiration during sedation for FMT administered via colonoscopy
Donor Screening Questionnaire
C. Kelly MD Brown University Alpert SOM
Exclusion Criteria
Risk of infectious agent
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Known exposure to HIV or viral hepatitis (within the previous 12 months.)
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High-risk sexual behaviors (examples: sexual contact with anyone with
HIV/AIDS or hepatitis, men who have sex with men, sex for drugs or money)
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Use of illicit drugs
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Tattoo or body piercing within 6 months
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Incarceration within previous 12 months
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Known current communicable disease
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Risk factors for variant Creutzfeldt-Jakob disease
Gastrointestinal co-morbidities
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History of inflammatory bowel disease
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History of irritable bowel syndrome, idiopathic chronic constipation, or
chronic diarrhea
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History of gastrointestinal malignancy
Other
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Antibiotic use within the preceding 90 days
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Recent ingestion of a potential allergen (e.g., nuts) where recipient has a
known allergy to this agent.
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Systemic autoimmunity, e.g., multiple sclerosis, connective tissue disease
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Chronic pain syndromes, e.g., chronic fatigue syndrome, fibromyalgia
Stool testing, Donor
• a) Clostridium difficile toxin B by PCR; if unavailable,
then evaluation for
toxins A and B by EIA.
• b) Bacterial culture for routine enteric pathogens
• c) Fecal Giardia antigen
• d) Fecal Cryptosporidium antigen
• e) Acid-fast stain for Cyclospora, Isospora and, if
antigen testing unavailable, Cryptosporidium
f) Ova and parasites
• g) Helicobacter pylori fecal antigen (for upper GI routes
of FMT administration)
Serologic testing: Donor
(unless otherwise stated, all tests should be
performed using FDA-approved test methods):
• a) HIV, type 1 and 2
• b) HAV IgM
• c) HBsAg, anti-HBc (both IgG and IgM), and antiHBs.
• d) HCV Ab
• e) RPR and FTA-ABS
Fecal Microbiota Transplantation Protocol
C. Kelly MD Brown University Alpert SOM
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Pre-Procedure Instructions
Donor
Report symptoms of infection which occur between screening and the day of
the procedure.
Take single dose of osmotic laxative on the evening prior to the procedure.
Patient
Stop oral vancomycin (or metronidazole) 3 days prior to procedure
Standard PEG colonoscopy bowel preparation
Fecal Solution Preparation
Universal precautions (gown, gloves, eye protection) during stool processing.
Fresh (< 6 hour) donor stool specimen
6-8 Tablespoons of fresh donor stool specimen added to ~1 Liter bottle of
sterile water or saline and shaken vigorously to emulsify.
Filtered through gauze if necessary
Fecal suspension drawn up into 60 cc Slip Tip syringes
Procedure
Informed consent for colonoscopy obtained including the additional theoretical
risk of infection related to fecal transfusion.
o
Document that examination of the colon is not adequate for cancer
screening purposes (stool infusion interferes with visualization).
Colonoscopy performed; biopsies taken if necessary
Upon withdrawal, dilute fecal suspension delivered through the colonoscope
(majority into the right colon)
Post-Procedure and Follow-Up
Patient encouraged to retain stool (if possible) for 30-45 minutes
Patient does not resume vancomycin
Patient asked to report symptoms of recurrent infection and stool is tested for
C. difficile only if these occur.
Open Biome
Methodology implemented for first public stool bank for FMT
www.openbiome.org
• Who are your donors?
Currently all of our donors are young researchers and scientists within the MIT,
Harvard, and Tufts communities, and young professionals from the Tufts University
area. (Reported Donor Alias: Vladimir Poo-tin NYT,2014)
• Does FMT have regulatory approval in the U.S.?
The FDA classifies fecal microbiota for FMT as an investigational drug, which typically
requires an Investigational New Drug application (IND). However, in July 2013, the
FDA issued guidance stating that it would exercise enforcement discretion for
physicians administering FMT to treat patients with refractory C. difficile infections. In
these cases, physicians may proceed without filing an IND, provided that they have
received the appropriate informed consent from the patient, at minimum indicating
that FMT is an investigational therapy, and discussing its potential risks.
Physicians who wish to use FMT in the treatment of all other indications are required
to do so as part of an Investigative New Drug application to the FDA.
UNM FMT via Colonoscopy Experience
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(22) patients : (15 females/ 7 males) (1) Fecal enema
Successful treatment: 21/22
•
Failure: (1)
Pt. hospitalized within 1 week with
worsening bladder outlet obstruction
requiring IV antibiotics for 1 week
•
Recurrence: (2)*
(1) Crohn’s Colitis- 12 months following FMT
after antibiotic treatment for peri-rectal abscess
(1) Chronic Pouchitis- placed on chronic suppressive
antibiotics with recurrence 6 months later
*both cases treated with second FMT with success.
UNM FMT via Colonoscopy Experience
• Complications:
Short Bowel Syndrome with recurrent CDI developed intraperitoneal
abscess 2 weeks later s/p IR drainage; no recurrent CDI
*Tarik Alhmoud, MD, Michael Gavin, MD. An unusual complication after a fecal microbiota transplant via colonoscopy. AJG,
S424, vol 109, Supplement 2, Oct 2014.
UNM FMT via Colonoscopy Experience
• Complications:
Post-infectious IBS- likely due to relapsing/recurrent C. Difficile
(c/w post-infectious IBS)
(2) cases document with (+) LHBT c/w SIBO.
Weight Gain After FMT
Alang N Kelly C Open Forum Infectious Diseases Volume 2, Issue 1 10.1093/ofid/ofv004
FMT for Relapsing C. Dif (36 yo female Baseline BMI-26)
• As per the patient’s request, her 16-year-old
daughter was chosen as the stool donor.
• Daughter’s weight was ∼140 pounds (BMI of 26.4), but it
increased later to 170 pounds.
• The patient presented again 16 months after FMT, and
reported an unintentional weight gain of 34 pounds. She
weighed 170 pounds and had become obese (BMI of 33).
Conclusion: The possible transmission of an obese phenotype
Gut microbiota from twins discordant for obesity
modulate metabolism in mice.
Ridaura VK Science 2013; 341:1241214.
• germ-free mice receiving a stool lavage
from an obese twin
• Developed significantly greater adiposity than
mice infused with the lean twin’s microbiota
Transfer of intestinal microbiota from lean donors
Vrieze A Gastroenterology 2012; 143:913–916.
• transfer of a lean microbiota to individuals
with metabolic syndrome
• improved insulin sensitivity when
compared with controls
• butyrate-producing bacterial strains
(activate intestinal gluconeogenesis)
increased in both lean stool samples
& lean individual’s intestinal biopsies
Recovery of the Gut Microbiome following Fecal
Microbiota Transplantation
Seekatz AM. mBio. 2014;doi:10.1128/mBio.00893-14.
• 16S rRNA sequencing on pre- and post-FMT samples of 14 patients who
had at least two recurrent CDI compared with samples from 10 donors
• Proteobacteria made up 48.2% of pre-FMT OTUs compared with 11.2% of
post-FMT (P<.001) and 0.73% of donor OTUs (P<.0001).
• Bacteroidetes constituted 1.3% of pre-FMT OTUs compared with 32.3% of
post-FMT (P<.0001) and 32.8% (P<.0001) of donor OTUs.
• Firmicutes and Bacteroidetes correlated with healthy post-FMT and donor
status while Proteobacteria correlated with pre-FMT.
*operational taxonomic units (OTUs)
C.Difficile infection (CDI) in IBD
• Prevalance: 8X greater than non-IBD pts.
(hospitalized)
• Outcomes: Increased risk for colectomy in UC
*Check stool for CDI with any flair in IBD!
Berg A Inflamm Bowel Dis Jan 2013;19:1
Oral, Capsulized, Frozen Fecal Microbiota Transplantation for
Relapsing Clostridium difficile Infection
Youngster I. JAMA. 2014;doi:10.1001/jama.2014.13875.
•
20 pts (median age, 64.5 years; range, 11-89 years)
- at least 3 episodes of mild to moderate C difficile infection
- failure of a 6- to 8-week taper with vancomycin or at least 2 episodes
of severe C difficile infection requiring hospitalization were enrolled.
• Healthy volunteers screened for donors/ FMT capsules were generated
Patients received 15 capsules on 2 consecutive days and were followed up
for symptom resolution and adverse events for up to 6 months.
• Resolution of diarrhea was achieved in 14 patients (70%) after a single
capsule-based FMT.
6 nonresponders: re-treated; 4 had resolution of diarrhea (90% overall)
Stool substitute transplant therapy for the eradication of
Clostridium difficile infection: ‘RePOOPulating’ the gut
Petrof E Microbiome 2013, 1:3 doi:10.1186/2049-2618-1-3
•
(33) isolates were recovered from a healthy
donor stool sample.
• Purified isolates were identified by 16S rRNA gene
sequencing and were subjected to antibiotic susceptibility
profiling.
• one-half (50 ml) of the solution was deposited in the region of
the cecum/proximal ascending colon and the other half was
drizzled throughout the transverse colon as the colonoscope
was withdrawn.
Stool substitute transplant therapy for the eradication of
Clostridium difficile infection: ‘RePOOPulating’ the gut
Petrof E Microbiome 2013, 1:3 doi:10.1186/2049-2618-1-3
• (2) patients were infected with the hyper virulent C.
difficile strain, ribotype 078.
• Following stool substitute treatment,
-reverted to their normal bowel pattern within 2 to 3 days
-remained symptom-free at 6 months.
• The analysis demonstrated that rRNA sequences,
-found in the stool substitute were rare in the
pre-treatment stool samples
-constituted over 25% of the sequences up to 6 months
after treatment.
Administration of Spores of Nontoxigenic Clostridium difficile
Strain M3 for Prevention of Recurrent C difficile Infection
Gerding DN ,JAMA. 2015;313(17):1719-1727. doi:10.1001/jama.2015.3725
• Clostridium difficile infection recurrence :
- 30% ( placebo)
- 11% (NTCD-M3)
(odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006)
Fulminant CDI
CT findings-colonic wall thickening, colonic dilation, ascites
Fulminant CDI
 Surgical treatment : organ failure, shock, vasopressors requirement,
worsening CT findings, peritonitis, or lack of response to max medical
therapy within 24-72 hrs.
 Surgical Procedure: Subtotal abdominal colectomy with
end ileostomy(rectal stump)
*Loop ileostomy and colonic lavage (PEG)- reduced morbidity and
preservation of the colon.
 30 day Mortality (CDI requiring ICU admission):
Surgical treatment: 34% Medical treatment:58%
Ann Surg 2007;245:267-72.