Clostridium difficile Colitis

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Clostridium difficile Colitis
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C. diff.Gram stain
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Bacteriology

• anaerobic gram-positive, spore-forming,
  toxin-producing bacillus
• first described in 1935
• C. difficile can exist in spore and vegetative
  forms.
• releases two potent exotoxins that mediate
  colitis and diarrhea
• toxin A ("enterotoxin")
• toxin B ("cytotoxin")

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Bacteriology

• Toxin A causes inflammation leading to intestinal
  fluid secretion, mucosal injury and inflammation

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Bacteriology

• Toxin B is essential for the virulence of C.
  difficile, and is approximately ten times more
  potent than toxin for mediating colonic mucosal
  damage

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Epidemiology

• C. difficile colonizes the colon of about 2
  percent of healthy adults.
• New colonization occurs predominantly by the
  fecal-oral route.
• Patients who become colonized are subsequently at
  risk for developing C. diff, primarily after
  treatment with antibiotics.

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Pathophysiology

• Colonization of the intestinal tract occurs via
  the fecal-oral route.
• Facilitated by disruption of normal intestinal
  flora due to antimicrobial therapy.
• The organism is capable of elaborating exotoxins
  that bind to receptors on intestinal epithelial
  cells, leading to inflammation and diarrhea.

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Pathophysiology

• Once intracellular, toxins A and B inactivate
  regulatory pathways mediated by proteins that are
  involved in cytoskeleton structure. This leads to
  shallow ulceration on the intestine mucosal
  surface.
• Both toxins also disrupt intercellular tight
  junctions.

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Pathophysiology

• Toxin B is essential for the virulence of C.
  difficile, and is approximately ten times more
  potent than toxin A in mediating colonic mucosal
  damage.
• Strains lacking toxin A can be as virulent as
  strains with both toxins.

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Hypervirulent Strain

•  A new, hypervirulent strain, NAP1/BI/027, has
  been implicated as the responsible pathogen in
  selected Clostridium difficile outbreaks since
  the early 2000s.
• produces binary toxin related to the iota-toxin
  found in Clostridium perfringens.
• produces substantially larger quantities of
  toxins A and B in vitro than other C. difficile
  strains.

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Clinical Manifestations

• Watery diarrhea
• Abdominal pain and cramping
• Low grade fever
• Leukocytosis
• Ileus
• Abdominal tenderness

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Extra-colonic Manifestations

• Protein-losing enteropathy with ascites
• C. difficile infection in the setting of chronic
  inflammatory bowel disease
• Extracolonic involvement
• --appendicitis
• --small bowel enteritis
• --extraintestinal involvementcellulitis,
  arthritis

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Diagnosis

• Anaerobic stool culture is the most sensitive
  testimpractical.
• Toxin assays--EIA
• specificity (up to 99 percent)
• variable sensitivity (60 to 95 percent)
• relatively high false negative rate since 100 to
  1000 pg of toxin must be present for the test to
  be positive

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Diagnosis

• Stool WBCs
• Sensitivefecal leukocytes never normal
• Low specificitybut clinical setting will help
• Cheap
• Readily available

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Diagnosis

• Sigmoidoscopy or colonoscopyfindings variable.
• CT scan--not usually necessary
• Non-specific
• Expensive
• Radiation exposure

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Treatment

• Initial episode Preferred metronidazole 500
  mg orally three times daily or 250 mg four times
  daily for 10 to 14 days.
• Alternative vancomycin 125 mg orally four times
  daily for 10 to 14 days First relapse Confirm
  diagnosis (see text) If symptoms are mild,
  conservative management may be appropriate If
  antibiotics are needed, repeat treatment as in
  initial episode

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Treatment

• Up to 50 percent of patients have positive stool
  assays for as long as six weeks after the
  completion of therapy. DONT repeat C. diff
  toxin assay as routine.

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Approach to Treatment Failure

• Recurrent disease often results from reinfection
  with the same or a different strain of C.
  difficile.
• Up to one-half of recurrent episodes are
  reinfections rather than relapses of infection
  with the original strain.

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Treatment Failure

• Risk factors for recurrence
• age gt65 years
• severe underlying medical disorders
• ongoing therapy with concomitant antibiotics

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Treatment Failure

• First relapse
• If symptoms are mild, conservative
  management may be appropriate.
• If antibiotics are needed, repeat
  treatment as in initial episode above

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Treatment Failure

• Second relapse Tapering and pulsed oral
  vancomycin 125 mg orally four times daily for 7
  to 14 days--125 mg orally twice daily for 7
  days--125 mg orally once daily for 7 days--125 mg
  orally every other day for 7 days--125 mg orally
  every 3 days for 14 days.
• Alternative fidaxomicin 200 mg orally twice
  daily for 10 days4

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Treatment Failure

• Subsequent relapse Vancomycin 125 mg orally
  four times daily for 14 days, followed by
  rifaximin 400 mg twice daily for 14 days.
• Alternative Fidaxomicin 200 mg orally twice
  daily for 10 days.

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Fecal Infusion

• Cure rates are high (up to 100 percent in small
  series), with a high level of patient acceptance.
• However, there is a concern about transmission of
  infectious agents to the stool recipient.

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Fecal Infusion

• 200 to 300 g of donor stool suspended in 200 to
  300 mL of sterile normal saline (homogenized
  briefly in kitchen blender to a liquid
  consistency).
• Administered via enema or NG or NE tube within 10
  minutes of preparation, repeated daily for five
  days.
• Can also be given as an enema or injected thru a
  colonoscope.

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Prevention--Goals

• Prevention of new colonization with the organism
• Prevention of C. diff colitis among patients
  already colonized by the organism

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Prevention

• Surveillance  track rates of C. diff.
• Contact precautions  patients should be placed
  on contact precautions, including gloves and
  gowns.
• Hand hygiene  Alcohol-based hand rub (ABHR) does
  NOT eradicate C. difficile spores. Centers for
  Disease Control recommends soap and water hand
  hygiene when caring for patients with C. diff.

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Prevention

• Stethoscope disinfection  alcohol wipes or gauze
  moistened with sterile water or alcohol.
• Environmental cleaningbleach solution.
• Restrict antibiotic usageclindamycin,
  fluroquinolones and cephalosporins
• Home hygieneclean surfaces with dilute bleach

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Summary

• Clostridium difficile infection is one of the
  most common hospital-acquired infections.
• Recurrences frequently caused by reinfection.
• Environmental hygiene is mandatory.
• Diagnosis and treatment need not be expensive.
• Antibiotic usage should be reduced.
• Pulse-taper therapy is effective for complicated
  recurrence.
• Fecal infusion therapy useful in severe
  refractory disease