Clostridium difficile: Epidemiology, Management and Focus on Fecal Bacteriotherapy/Fecal Microbiota Transplantation Jayesh Patel, MD, DTM&H Infectious Disease Consultant Chair Infection Prevention and Pharmacy/Therapeutics/Nutrition (Skyline)
Feb 25, 2016
Clostridium difficile:Epidemiology, Management
and Focus on Fecal Bacteriotherapy/Fecal Microbiota Transplantation
Jayesh Patel, MD, DTM&HInfectious Disease ConsultantChair Infection Prevention and
Pharmacy/Therapeutics/Nutrition (Skyline)
C. difficile management :Financial disclosure
No financial conflict of interest
( Past speaker for Dificid)
Objectives: C. difficile
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
Clostridium difficile 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
C. difficile: Epidemic Strain 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
Epidemiology
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
Risk Factors
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
Prevention of Transmission 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
Clinical Manifestations
Diarrhea, abdominal pain, N/V, fever, loss of appetite
Pseudomembranous colitis
Toxic megacolon Perforation of colon
Severe sepsis Death
Testing in C. difficile ? Smell WBC , creatinine, albumin Stool testing
Culture for C. difficile — slow— labor intensive, technical expertise— expensive— requires second test for toxin
detection
Stool Testing
Cell Cyto-toxicity Neutralization Assay— Toxin B detection only— Slow, Labor Intensive/technical
expertise— Moderate sensitive, High specificity
Stool Testing
Antigen detection ( Glutamate DeHydrogenase EIA)— Highly Sensitive— Rapid— Cheaper— Not specific
Stool Testing
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
Stool Testing
PCR — Toxin B gene— Very sensitive and specific— Rapid if done in house— Expensive
Multistep Testing
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
C. Difficile treatment:Metronidazole 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
Vancomycin 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
Nitazonxanide
Indication: index infection or recurrent CDI
Administration: 500 mg PO bid for 10 days
More studies are needed to clarify its role in CDI.
Rifaximin
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.
Fidaxomicin
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
Toxin Binders 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.
Immunoglobulins
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
ProbioticsSaccharomyces boulardi 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)
Other treatments
Bacitracin suspensionRifampinTeichoplaninTigecyclineSurgery: ColectomyFecal bacteriotherapy/FMT
Fecal Microbiota Transplantation 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.
Case Report
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.
Case Report
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.
Case Report
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
Case report: CT Abdomen
Case Report
Treatment: IV fluids, Vanco PO, Metronidazol, Nitozoxanide
Poor response: ? Fidoxamicin ? FMT ?Colectomy
Patient elects to have FBT/FMT
Case Report
Approx. 70 grams donor stool instilled via Naso-duodenal tube, partial response, 2nd instillation of fresh 100 gram stool next day. Diarrhea resolves 3rd day.
Patient observed 2 more days than discharged home free of symptoms
Patient free of symptoms after 6 months
Procedure for FBT/FMT
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.
Consents and Education
FBT/FMT Policy and ProcedurePatient ConsentPatient Education BrochureDonor ConsentDonor InstructionBowel Motion Record
Recipient testing
All recipients will have the following laboratory tests:— HIV antibody— Hepatitis A antibody— Hepatitis B surface antigen— Hepatitis C antibody
DONOR:
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
Patient Prep
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
Stool Specimen Preparation for Lower GI Administration 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.
Stool Specimen Preparation for Lower GI Administration 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.
Stool Preparation for Upper GI Administration 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.
FMT via Upper GI Tract
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.
FMT Via Upper GI Tract
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.
Naso-duodenal Tube Placement
FMT: Upper GI Tract Route
FMT: Upper GI Tract Route
Goodbye !
Listen to your mother:
Don’t forget to wash your hands after using
the restroom and before eating!