1. Jayesh Patel, MD, DTM&H Infectious Disease Consultant Chair Infection Prevention and Pharmacy/Therapeutics/Nutrition (Skyline)

2.  No financial conflict of interest  ( Past speaker for Dificid)

3.  Learn current epidemiology of C. difficile infection  Understand clinical presentation of C. difficile disease  Understand testing methodology for C. difficile infection  Learn about prevention and treatment of C. difficile infection  Learn about rationale and methods of treatment by fecal microbiota transplantation

4.  Gram positive anaerobic bacillus  Produces spores  Commensal intestinal flora in 2-5 % of healthy adults, over 50% of infants  Fecal-oral transmission  Colonizes 20-40 % hospitalized patients  Produces toxins A, B, and Binary toxin

5.  NAP1/BI/027strain of C. difficile  "North American Pulse-field type 1" pattern (on gel electrophoresis) and a "BI" pattern (on restriction endonuclease analysis), and type "027" (on ribotyping)  Resistance to quinolone antibiotics  Hypersporulation  Binary toxin production  High levels of toxin A,B (20 x greater)  High morbidity and mortality

6.  USA 15,000 – 20,000 deaths annually, rising  20 % of all episodes of antibiotic associated diarrhea are due to C. difficile  4-10 cases per 10,000 patient days  Relapse occurs in over 20 % of cases  Increase in average hospital cost : $ 27,000  Over 1 billion dollars in costs annually

7.  Current and prior antibiotics  Elderly  Immunocompromized  Hospital stay, nursing home residence  NG tube, tube feeding  Recent Endoscopy, Gastrointestinal surgery  Proton pump inhibitors, H2 blockers, Chemotherapy

8.  Private rooms  Contact isolation: gloves, gowns  Hand washing ( instead of alcohol based )  Special entry signs  EPA approved sporicidal agents, diluted bleach for cleansing all environmental surfaces and reusable devices  Isolation till diarrhea resolved or discharged

9.  Diarrhea, abdominal pain, N/V, fever, loss of appetite  Pseudomembranous colitis  Toxic megacolon  Perforation of colon  Severe sepsis  Death

10.  ? Smell  WBC, creatinine, albumin  Stool testing  Culture for C. difficile — slow — labor intensive, technical expertise — expensive — requires second test for toxin detection

11.  Cell Cyto-toxicity Neutralization Assay — Toxin B detection only — Slow, Labor Intensive/technical expertise — Moderate sensitive, High specificity

12.  Antigen detection ( Glutamate DeHydrogenase EIA) —Highly Sensitive —Rapid —Cheaper —Not specific

13.  Toxin Enzyme Immuno Assay — Detects toxin A and B — Quick, inexpensive — Less sensitive — Toxin is heat labile so testing must be done within 2 hours or keep stool sample refrigerated

14.  PCR — Toxin B gene — Very sensitive and specific — Rapid if done in house — Expensive

15.  Antigen negative: no further testing, not C. difficile  Antigen positive, Toxin positive: has C. difficile  Antigen positive, Toxin negative: send for PCR — PCR negative: not C. difficile — PCR positive: has C. difficile

16.  Indication: mild to moderate CDI  Administration: 500 mg PO or IV tid for 10- 14 days  First line therapy for mild to moderate CDI, but increasing rates of refractory infection are being observed

17.  Indication: Moderate to severe CDI  Administration: ~125-500 mg PO qid for 10- 14 d  Oral, nasogastric, or rectal therapy may be combined with IV metronidazole in critically ill patients.  Tapered/Pulse therapy for recurrent CDI

18.  Indication: index infection or recurrent CDI  Administration: 500 mg PO bid for 10 days  More studies are needed to clarify its role in CDI.

19.  Indication: recurrent CDI  Administration: 200 mg PO bid to 400 mg PO tid for 28 d. May be given as a “chaser” after completion of vancomycin therapy for recurrent CDI.  More controlled studies needed to decide best use of this drug.

20.  Indication: index infection of recurrent CDI  Administration: 200 mg PO bid for 10 d  Non-inferior to vancomycin and is associated with a significantly lower rate of recurrent infection  Expensive

21.  Indication: symptomatic adjunct to antibiotic treatment  Administration: Cholestyramine 4 g PO tid or qid. ?? Duration  Toxin binders such as cholestyramine should be used to control symptomatic diarrhea but not as the only treatment.

22.  Indication: refractory CDI  Administration: IV infusion at a dose of 400 mg/kg (IVIG) of body weight given with antibiotic therapy.  Enhances overall efficacy of treatment and reduces further recurrences.  Expensive

23.  Indication: prevention of recurrent CDI  Administration: 500 mg PO bid for 28 d. Usually started after 7 days of antibiotic treatment.  Avoid using in severely immunosuppressed patients; should not be given chronically.  (Lactobacillus not proven to help)

24.  Bacitracin suspension  Rifampin  Teichoplanin  Tigecycline  Surgery: Colectomy  Fecal bacteriotherapy/FMT

25.  Indication: recurrent/refractory CDI; unclear role in severely ill CDI patients as first-line therapy.  Administration: stool suspension from a healthy donor administered by nasogastric/NJ tube, via colonoscopy or enema.  Excellent preliminary results in patients with severe and refractory disease. Best methodology is yet to be clarified.

26.  62 yr old white male  Had URI ( ? Viral), got abx. and 3 days later, develops diarrhea, becomes severe, Metronidazol started. Gets worse, abd cramping, weakness, mucousy stools, stools every ½ hour.  PMH: splenectomy, multiple sinus surgeries, fracture/laceration finger one month earlier, had pinning and got prophylactic antibiotic.

27.  Admitted to Hospital  WBC 12.9k, Cr 1.2, C. diff Ag/Toxin positive  Oral vancomycin started  Slow/poor response, Nitozoxanide added  Slow improvement, discharged on oral Nitozoxanide.  Nitozoxanide not covered by insurance so changed to Metronidazol. Had 1-2 soft/loose stools daily.

28.  2 days after completing Metronidazol, develops explosive diarrhea  20 BM/day, nausea, chills, abdominal pain, weak  Readmitted  Ill looking, T 100.1, HR 110, BP 100/52  Abdomen tender

30.  Treatment: IV fluids, Vanco PO, Metronidazol, Nitozoxanide  Poor response: ? Fidoxamicin ? FMT ?Colectomy  Patient elects to have FBT/FMT

31.  Approx. 70 grams donor stool instilled via Naso-duodenal tube, partial response, 2nd instillation of fresh 100 gram stool next day. Diarrhea resolves 3 rd day.  Patient observed 2 more days than discharged home free of symptoms  Patient free of symptoms after 6 months

32.  Diagnosis will be confirmed by Gastroenterologist or Infectious Disease Specialist.  Gastroenterologist or Infectious Disease Specialist wishing to use(FBT) will notify designated departments to schedule the testing/procedure, and discuss the process with donor and recipient for Informed Consent.

33.  FBT/FMT Policy and Procedure  Patient Consent  Patient Education Brochure  Donor Consent  Donor Instruction  Bowel Motion Record

34.  All recipients will have the following laboratory tests: — HIV antibody — Hepatitis A antibody — Hepatitis B surface antigen — Hepatitis C antibody

35.  Ideally the stool transplant donors should be related to the recipient but not the spouse, significant other or a family household member. They should be healthy and have not received antimicrobial therapy in the last 2 months.  The donor should have normal bowel habits and be free of blood-borne or stool-borne pathogens.  Screening tests prior to the transplant  Acute Hepatitis Panel, HIV antibody, and CBC  Donor stool testing for Clostridium difficile toxin, Stool culture, Cryptosporidium stain, Stool O & P

36.  Obtain signed consent for Fecal Bacteriotherapy/FMT  Start Liquid diet the day prior to the scheduled FBT/FMT  Cleanse patients’ bowel using 3-4 liters of Golytely, the day before FBT/FMT  Give PPI agent day of procedure for upper GI administration  Stop antibiotics 24-48hr before FMT

37.  Obtain 250-300 gms (approx one cup) of fresh stool from donor as soon as possible prior to the transplantation procedure, never more than 4 hours prior.  Using a blender, add stool to 250ml of Normal Saline or Sterile Water. Mix until stool particles are dispersed throughout the liquid  Remove large particles by straining the stool/liquid mixture twice, utilizing strainer.

38.  Mixture should be administered within 2 hours of preparation. No more than 6 hours should elapse between stool specimen collection and fecal administration.  Administer as Enema or by Colonoscopy into terminal ileum and colon.  Enema can be given by standard enema set or by Fecal Management System (ActiFlo). Retain enema for 1-2 hours.  Repeat enema with fresh stool next day if ordered.

39.  On the day of the procedure, obtain 100 g (approx 1/3 to 1/2 cup) of donor stool.  Using a blender, add stool to 100 ml (or necessary amount to facilitate installation) of Normal Saline or Sterile water. Mix until stool particles are dispersed throughout the solution.  Remove large particles by straining the stool/saline mixture twice, utilizing a strainer.  Transfer solution into catheter tip syringes for transport to patient.

40.  Place NG tube or Naso-duodenal tube morning of procedure in radiology department.  If NJ tube is used, it is inserted into Jejunum through endoscope.  Don gown, gloves, mask, and eye protection.

41.  Using a syringe administer the freshly mixed stool via NJ/ Dobhoff tube.  After stool installation, flush with 50ml of normal saline. (DO NOT REMOVE NJ/DOBHOFF TUBE).  Repeat stool infusion procedure next day.  Do not remove NJ/Dobhoff tube until ordered by physician.

45.  Listen to your mother: Don’t forget to wash your hands after using the restroom and before eating!