Clostridium difficile: Epidemiology, management

Report
Jayesh Patel, MD, DTM&H
Infectious Disease Consultant
Chair Infection Prevention and
Pharmacy/Therapeutics/Nutrition (Skyline)
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No financial conflict of interest
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( Past speaker for Dificid)
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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
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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
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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
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USA 15,000 – 20,000 deaths annually, rising
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20 % of all episodes of antibiotic associated
diarrhea are due to C. difficile
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4-10 cases per 10,000 patient days
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Relapse occurs in over 20 % of cases
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Increase in average hospital cost : $ 27,000
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Over 1 billion dollars in costs annually
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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
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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
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Diarrhea, abdominal
pain, N/V, fever, loss
of appetite
Pseudomembranous
colitis
Toxic megacolon
Perforation of colon
Severe sepsis
Death
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? Smell
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WBC , creatinine, albumin
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Stool testing
 Culture for C. difficile
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slow
labor intensive, technical expertise
expensive
requires second test for toxin detection
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Cell Cyto-toxicity Neutralization Assay
— Toxin B detection only
— Slow, Labor Intensive/technical expertise
— Moderate sensitive, High specificity
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Antigen detection ( Glutamate
DeHydrogenase EIA)
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Highly Sensitive
Rapid
Cheaper
Not specific
 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
 PCR
— Toxin B gene
— Very sensitive and specific
— Rapid if done in house
— Expensive
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Antigen negative: no further testing, not C.
difficile
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Antigen positive, Toxin positive: has C. difficile
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Antigen positive, Toxin negative: send for PCR
— PCR negative: not C. difficile
— PCR positive: has C. difficile
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Indication: mild to moderate CDI
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Administration: 500 mg PO or IV tid for 1014 days
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First line therapy for mild to moderate CDI,
but increasing rates of refractory infection
are being observed
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Indication: Moderate to severe CDI
Administration: ~125-500 mg PO qid for 1014 d
Oral, nasogastric, or rectal therapy may be
combined with IV metronidazole in critically
ill patients.
Tapered/Pulse therapy for recurrent CDI
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Indication: index infection or recurrent CDI
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Administration: 500 mg PO bid for 10 days
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More studies are needed to clarify its role in
CDI.
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Indication: recurrent CDI
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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.
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More controlled studies needed to decide
best use of this drug.
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Indication: index infection of recurrent CDI
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Administration: 200 mg PO bid for 10 d
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Non-inferior to vancomycin and is associated
with a significantly lower rate of recurrent
infection
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Expensive
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Indication: symptomatic adjunct to antibiotic
treatment
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Administration: Cholestyramine 4 g PO tid
or qid. ?? Duration
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Toxin binders such as cholestyramine should
be used to control symptomatic diarrhea but
not as the only treatment.
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Indication: refractory CDI
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Administration: IV infusion at a dose of 400
mg/kg (IVIG) of body weight given with
antibiotic therapy.
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Enhances overall efficacy of treatment and
reduces further recurrences.
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Expensive
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Indication: prevention of recurrent CDI
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Administration: 500 mg PO bid for 28 d.
Usually started after 7 days of antibiotic
treatment.
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Avoid using in severely immunosuppressed
patients; should not be given chronically.
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(Lactobacillus not proven to help)
Bacitracin suspension
Rifampin
Teichoplanin
 Tigecycline
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Surgery: Colectomy
Fecal bacteriotherapy/FMT
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Indication: recurrent/refractory CDI; unclear role in
severely ill CDI patients as first-line therapy.
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Administration: stool suspension from a healthy
donor administered by nasogastric/NJ tube, via
colonoscopy or enema.
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Excellent preliminary results in patients with severe
and refractory disease. Best methodology is yet to
be clarified.
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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.
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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.
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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
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Treatment: IV fluids, Vanco PO,
Metronidazol, Nitozoxanide
Poor response: ? Fidoxamicin ? FMT
?Colectomy
Patient elects to have FBT/FMT
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
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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.
FBT/FMT Policy and Procedure
Patient Consent
Patient Education Brochure
 Donor Consent
 Donor Instruction
 Bowel Motion Record
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All recipients will have the following
laboratory tests:
— HIV antibody
— Hepatitis A antibody
— Hepatitis B surface antigen
— Hepatitis C antibody
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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
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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
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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.
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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.
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.
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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.
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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.
 Listen to your mother:
Don’t forget to wash your
hands after using the restroom
and before eating!

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