Clostridium DifficileAssociated Diarrhea CDAD

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Clostridium Difficile-Associated Diarrhea (CDAD)

• Manuel Mah, MD, MPH
• manuelmah_at_crha-health.ab.ca

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Overview

• Clinical context and terminology
• Microbiology
• Pathogenesis and Reservoirs
• Definition, syndromes, complications
• Diagnosis, treatment, relapses
• Prevention

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Nosocomial diarrhea
Antibiotic-associated diarrhea (3 to 30 of pts
on antibiotics)
CDAD (20 to 30 of A-AD)
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Confusing terminology

• Antibiotic-associated diarrhea
• C. difficile is only one cause
• Clostridium difficile-associated diarrhea
• diarrhea positive stool test
• Clostridium difficile colitis
• underlying pathologic process
• Pseudomembranous colitis
• endoscopic demonstration of exudative lesions
• Toxic megacolon
• radiologic and surgical diagnosis

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Disruption of protective colonic flora (AB or AN)
Colonization with toxigenic C. difficile by
fecal-oral transmission
Toxin A and B production
A/B Cytoskeletal damage, loss of tight
junctions. A Mucosal injury, inflammation, fluid
secretion.
Colitis and Diarrhea
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Reservoirs for toxigenic C. difficile

• 15 to 70 of healthy neonates (to age 1 y)
• lt3 of healthy adults (up to 15)
• 10 to 20 of hospitalised patients, especially
  with antibiotics
• Most disease-causing strains are exogenously
  acquired
• hospital environment
• HCW hands

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Operational definition of CDAD

• Diarrhea
• 6 watery stools over 36 hours
• 3 unformed stools in 24 hours for 2 days
• 8 unformed stools over 48 hours
• Pseudomembranes seen at endoscopy OR positive
  stool test
• No other etiology for diarrhea
• Antibiotic exposure in the past 6-8 weeks

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Syndromes and complications

• Asymptomatic colonization
• Diarrhea (mild to severe)
• Colitis /- pseudomembranes (endoscopy)
• Toxic megacolon (radiology)
• Colonic perforation/peritonitis
• Sepsis and acute abdomen without diarrhea (ileus)

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Diagnosis of CDAD

• Endoscopy (pseudomembranous colitis)
• Culture
• Cell culture cytotoxin test
• EIA toxin test
• PCR toxin gene detection

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Anaerobic culture

• CCFA cycloserine, cefoxitin, fructose agar (a
  selective and differential medium)
• Very sensitive, but does not differentiate
  between toxin and non-toxin strains (must add a
  toxin test to increase specificity)
• Essential for epidemiologic studies
• No longer offered routinely cost issue

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Cell culture cytotoxin test

• Stool filtrate added to mammalian cell line with
  and without toxin-neutralizing antibody
• The sample without neutralizing antibody shows
  cytopathic effect (ie, dead clumps of rounded
  cells)
• The sample with neutralizing antibody shows
  intact cell monolayer

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EIA toxin tests

• Can detect toxin A, toxin B, or both
• Rapid, cheap, and specific
• Less sensitive than cytotoxin test
• Toxin A tests will miss rare C. difficile
  isolates that produce toxin B only (Toxin
  A-negative, toxin B-positive outbreak, Winnipeg,
  1998)

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Performance characteristics of diagnostic tests
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Toxin testing issues Just say No!

• Should we screen and treat toxin-positive,
  asymptomatic contacts?
• Should a negative toxin test be repeated? (maybe)
• Should a positive toxin test be repeated?
• Do we need a test-of-cure?
• Is toxin testing useful in infants (lt age 1 y)?

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Treatment - 1

• 1. Discontinue offending agent or modify to less
  offensive agent (successful in 20 to 25)
• 2. Replace fluids and electrolytes
• 3. Avoid antiperistaltic agents may worsen
  diarrhea or precipitate toxic megacolon
• 4. If conservative measures not effective or
  practical, give oral metro for 10 days

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Treatment - 2

• 5. Do not treat asymptomatic C. difficile
  colonization
• 6. Retreat first-time recurrences with the same
  regimen used to treat the initial episode
• 7. Avoid vancomycin if possible
• 8. Do not treat nosocomial diarrhea empirically
  without testing since even during outbreaks, lt30
  have CDAD

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Relapses

• Occur in 20 to 30 of CDAD patients
• Usually 1 to 3 wks after termination of Rx
• Relapse is recurrent disease with same strain
  (persistence of C. difficile spores)
• Some relapses are due to re-acquisition of same
  strain from environment
• Reinfection is recurrent disease with new strain

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Unproven therapies

• Tapering course of standard antimicrobials
• Yeast (Saccharomyces boulardii) with AB
• Cholestyramine
• Lactobacillus acidophilus
• Nontoxigenic C. difficile (oral)
• Bacterial enemas
• Rectal infusion of normal feces
• Synsorb Cd (toxin binding agent)

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Infection control measures proven to prevent CDAD

• Glove use
• Single-use rectal thermometers
• Antibiotic usage restriction

Infection control measures that probably help

• Handwashing
• Private room or cohorting
• Endoscope disinfection

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On average, CDAD happens because

• Healthcare workers dont wash their hands
• Administrators dont pay to keep the hospital
  clean
• Doctors dont use antibiotics wisely