1. C.Difficile an epidemic that is waiting for answers
Michael Gavin MD Division of Gastroenterology University of New Mexico

2. 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 (within 30 days of infection)
Persons 65 years of age or older, whites & females had higher incidences than their comparators.

3. 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.)

4. C. Difficile Infection in the Elderly Keller JM Clinics in Geriatric Medicine 2014, 30:79-83.
Increase rates- Severe Disease Medical complications Mortality

5. 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.

6. 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

7. 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: (All sites: 48.2)
Health Care–Associated CDI Cases: Incidence per 100,000 Persons: (All sites: 92.8)

8. Burden of Clostridium difficile Infection in the United States n engl j med 372;9 nejm.org february 26, 2015
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)

9. 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

10. 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

11. 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

12. Pseudomembranes

13. 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

14. Antibiotics
Prior Exposure Antibiotics: 85% pts with CDI within 28 days
Antibiotic Utilization: Increased duration & multiple antibiotics
Clindamycin ( )
Parenteral Cephalosporins ( ’s)
Fluoroquinolones (2000’s): inpts & outpts

15. 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

16. Commercially available tests
EIA against toxins (A&B)
Detect both toxins
Greater sensitivity
False negatives high
Hence the classic thought of multiple tests
GDH (glutamase dehydrogenase)
Common antigen
High sensitivity
Low specificity
Can rule-out C. difficile
PCR: new test with sensitivity and specificity

17. 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.

18. Testing (Tricore) PCR toxin B gene:
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: Ileus- rectal swap)
*Resubmissions after 7-day period

19. Diagnosis Stool tests:
Identification of C. diff toxins A and/or B (Sensitivity %; Specificity 99%)
EIA (Sensitivity 60-95%; Specificity 99%)
PCR (Sensitivity 94%; Specificity 97%)

20. Diagnosis: Treat the Pt. Not the Test Polage CRJAMA Intern Med. doi:10
Diagnosis: Treat the Pt. Not the Test Polage CRJAMA Intern Med. doi: /jamainternmed
(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.

21. 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)

22. 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

23. SHEA-IDSA Guideline Clinical Case Defination Initial Episode:
Laboratory Data and Clinical Findings
Initial Episode:
Mild or Moderate
Severe
Severe, complicated
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

24. SHEA-IDSA Guideline Initial Episode Treatment Mild or Moderate:
Severe:
Severe, complicated
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

25. 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 days
then
125 mg po bid 7days
125 mg po qd 7 days
125 mg po qod 2-8 weeks

26. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile  McFarland L Elmer G Surawicz C ACG (2002) 97, 1769–1775
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).

27. Recurrent or relapsing CDI Surawicz CM, Brandt LJ, Binion DG et al
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.

28. Refractory CDI Surawicz CM, Brandt LJ, Binion DG et al
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.

29. Severe CDI Surawicz CM, Brandt LJ, Binion DG et al
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.

30. Complicated CDI Surawicz CM, Brandt LJ, Binion DG et al
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.

31. 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 :

32. Vancomycin (+)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)

33. 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%)

34. (629) Adults(CDI): FID 200mg bid vs VAN 125mg qid 10 days
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

35. 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: %
Subgroup analysis: No significant difference
Severity of Disease Patient’s age Recurrent CDI

36. Fecal Microbiota Transplant Recurrent/Refractory CDI (RCDI)
Antibiotic-associated diarrhea (CDI?) pts treated with human fecal enemas (cure: 4/4) Eiseman Surgery 1958;444:
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, (1989)

37. 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:
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 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, (2010)

38. Fecal Microbiota Transplant Colonoscopy
12 of 12 pts. with RCDI cured: cc injected from distal TI to rectum Yoon SS & Brandt, LJ J. Clin Gastroenterol. 44, (2010)
18 of 19 pts with RCDI cured: Rohlke F, Surawicz J Clin Gastroenterol. 44, (2010)
25 of 26 pts. with RCDI cured: Kelly, C J Clin Gastroenterol. Feb;46(2):145-9 (2012)

39. 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)

40. FMT for Treatment of Clostridium difficile Infection in Immunocompromised Patients Kelly CR. Am J Gastroenterol. 2014;doi: /ajg
 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

41. Donor Screening Questionnaire C. Kelly MD Brown University Alpert SOM
Exclusion Criteria
Risk of infectious agent
Known exposure to HIV or viral hepatitis (within the previous 12 months.)
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)
Use of illicit drugs
Tattoo or body piercing within 6 months
Incarceration within previous 12 months
Known current communicable disease
Risk factors for variant Creutzfeldt-Jakob disease
Gastrointestinal co-morbidities
History of inflammatory bowel disease
History of irritable bowel syndrome, idiopathic chronic constipation, or chronic diarrhea
History of gastrointestinal malignancy
Other
Antibiotic use within the preceding 90 days
Recent ingestion of a potential allergen (e.g., nuts) where recipient has a known allergy to this agent.
Systemic autoimmunity, e.g., multiple sclerosis, connective tissue disease
Chronic pain syndromes, e.g., chronic fatigue syndrome, fibromyalgia

42. 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)

43. 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 anti-HBs.
d) HCV Ab
e) RPR and FTA-ABS

44. Fecal Microbiota Transplantation Protocol C
Fecal Microbiota Transplantation Protocol C. Kelly MD Brown University Alpert SOM
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.
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 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.

45. 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.  

46. UNM FMT via Colonoscopy Experience
(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.

47. 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.

48. 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.

49. Weight Gain After FMT Alang N Kelly C Open Forum Infectious Diseases Volume 2, Issue /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

50. germ-free mice receiving a stool lavage from an obese twin
Gut microbiota from twins discordant for obesity modulate metabolism in mice Ridaura VK Science 2013; 341:
germ-free mice receiving a stool lavage from an obese twin
Developed significantly greater adiposity than
mice infused with the lean twin’s microbiota

51. 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

52. Recovery of the Gut Microbiome following Fecal Microbiota Transplantation Seekatz AM. mBio. 2014;doi: /mBio
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)

53. 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

54. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection Youngster I. JAMA. 2014;doi: /jama
 20 pts (median age, 64.5 years; range, 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)

55. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut Petrof E Microbiome 2013, 1:3  doi: /
 (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.

56. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut Petrof E Microbiome 2013, 1:3  doi: /
(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.

57. - 30% ( placebo) - 11% (NTCD-M3)
Administration of Spores of Nontoxigenic Clostridium difficile Strain M3 for Prevention of Recurrent C difficile Infection Gerding DN ,JAMA. 2015;313(17): doi: /jama
Clostridium difficile infection recurrence :
- 30% ( placebo)
- 11% (NTCD-M3)
(odds ratio [OR], 0.28; 95% CI, ; P = .006)

58. Fulminant CDI CT findings-colonic wall thickening, colonic dilation, ascites

59. Fulminant CDI
Surgical treatment : organ failure, shock, vasopressors requirement, worsening CT findings, peritonitis, or lack of response to max medical therapy within 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: