Gastroenterology Book

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Clostridium difficileAka: Pseudomembranous colitis

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  1. See Also
    1. Diarrhea
    2. Infectious Diarrhea
  2. Epidemiology
    1. Dramatic increase in cases in last decade
  3. Pathophysiology
    1. Anaerobic, Gram Positive, spore-forming bacillus
    2. New virulent strain: B1 NAP1
      1. Toxin A/B levels are >16x higher than other strains
    3. Sequence of infection
      1. Normal colonic bacteria disturbed (e.g. antibiotics)
      2. Exposure to C. difficile
        1. C. difficile is commensal in only 3% of patients
        2. C. difficile survives in hospital room >40 days
        3. Occurs in 50% of those hospitalized >4 weeks
      3. Colonization with Clostridium difficile
        1. Results in carrier state (asymptomatic) or
        2. Mild Diarrheal illness or
        3. Severe illness (pseudomembranous colitis)
  4. Risk Factors
    1. Highest risk patients
      1. Elderly
      2. Debilitated patients
      3. Immunocompromised patients
    2. Proton Pump Inhibitors (raise gastric pH)
    3. Recent antibiotic use
      1. General
        1. All antibiotics can cause C. difficile Diarrhea
        2. Broad-spectrum agents are highest risk
      2. Most common antibiotic causes
        1. Ampicillin or Amoxicillin
        2. Cephalosporins
        3. Clindamycin
      3. Less common antibiotic causes
        1. Macrolides (e.g. Erythromycin, Azithromycin)
        2. Tetracyclines antibiotics (e.g. Doxycycline)
        3. Sulfonamides (e.g. Bactrim)
        4. Trimethroprim
        5. Quinolones (e.g. Ciprofloxacin)
      4. Rare antibiotic causes
        1. Parenteral Aminoglycosides
        2. Metronidazole (used for treatment)
        3. Vancomycin (used for treatment)
  5. Symptoms
    1. Asymptomatic carrier state is common
    2. Diarrhea (variably present)
      1. Timing
        1. Incubates for 2-7 days after colonization
        2. Most cases occur on days 4-9 of antibiotic course
        3. Onset <14 days after antibiotics in 96% of cases
        4. All cases occur within 3 months of antibiotics
        5. Olson (1994) Infect Control Hosp Epidemiol 15:371
      2. Characteristics
        1. Frequent, loose Bowel Movements
        2. Mucus and occult blood often present
        3. Crampy Abdominal Pain
      3. Associated findings
        1. Fever
        2. Asymmetric oligoarticular large joint arthralgia
  6. Labs
    1. Complete Blood Count
      1. Leukocytosis variably present
  7. Radiology: Abdominal XRay
    1. Dilated colon: >7 cm in greatest diameter
    2. Small bowel dilation or air-fluid levels may be present
    3. Mucosal edema or thumbprinting may also be present
  8. Diagnosis
    1. Clostridium difficile Toxin
    2. Endoscopy (Flexible Sigmoidoscopy or Colonoscopy)
      1. Not recommended in most cases
      2. May be indicated if diagnosis is unclear
      3. Findings: Mucosal lesions with pseudomembranes
  9. Differential Diagnosis
    1. Antibiotic intolerance (resolves off antibiotics)
    2. Infectious enteritis
      1. Acute Gastroenteritis
      2. Amebic dysentary
    3. Inflammatory Bowel Disease
    4. Ischemic colitis
  10. Management: General Measures
    1. Discontinue antibiotic
      1. Diarrhea resolves in up to 25% of cases with stopping
      2. If antibiotic required, choose one with lower risk
    2. Indications to start antibiotics immediately (empiric)
      1. Older patients
      2. Multiple comorbid conditions
      3. Antibiotics can not be discontinued
      4. Severe disease
        1. Persistent Diarrhea
        2. Dysentary (fever, Leukocytosis)
    3. Avoid medications that could worsen condition
      1. Opioid
      2. Antidiarrheal agents
    4. Do not retest for toxin post-treatment if asymptomatic
      1. May be positive, but does not require treatment
  11. Management: Adults
    1. Metronidazole 500 mg PO qid for 10-14 days
      1. Drug of choice due to low cost and 98% effective
      2. Other dosing
        1. Lower dose: 250 mg PO q6 hours for 10-14 days
        2. Parenteral: 500 mg IV q8 hours for 10-14 days
    2. Vancomycin 125-500 mg PO qid for 10-14 days
      1. Second line agent to Metronidazole
        1. Risk of promoting Vancomycin resistance
        2. Very expensive ($800 per course)
      2. Only effective for C. Difficile if dosed PO
      3. Use low dose (125 mg) in most patients
      4. Use high dose in severe illness
  12. Management: Child
    1. Mild to Moderate disease: Metronidazole (Flagyl)
      1. Metronidazole 7 mg/kg (maximum 500 mg) tid for 7 days
    2. Severe disease: Vancomycin
      1. Vancomycin 5 mg/kg (maximum 125 mg) q6 hours x7 days
  13. Management: Recurrence
    1. Vancomycin taper
      1. Starting dose 125 mg every 6 hours for 1 week
      2. Taper to 125 mg every 12 hours for 1 week
      3. Taper to 125 mg daily for 1 week
      4. Taper to 125 mg every other day for 1 week
      5. Taper to 125 mg every third day for 2 weeks
    2. Probiotics
      1. Saccharomyces boulardii (avoid if immunocompromised)
        1. Dose 250 mg PO bid to tid for 1 month
        2. Has also been used with Vancomycin 500 mg PO qid
  14. Management: Fulminant disease
    1. Flagyl IV 500 mg every 8 hours and
    2. Vancomycin 500 mg PO qid and
    3. Vancomycin enema 500 mg in 100 cc NS q6 hours
      1. Delivered by foley in rectum, 30 cc balloon
      2. Balloon inflated for 60 minutes after dose
  15. Findings of improvement (assess on day 5)
    1. Fever resolves within first 2 days
    2. Diarrhea resolves within first 4 days
  16. Complications
    1. Toxic Megacolon
    2. Bowel perforation
    3. Dehydration or electrolyte abnormality
  17. Prevention
    1. Avoid broad-spectrum antibiotic use
    2. Probiotics may be considered in recurrent cases
    3. Prevent Clostridium difficile spore spread
      1. Spores are resistant to Alcohol and antiseptics
      2. Practice good hygiene
        1. Hand washing
        2. Disinfect surfaces
          1. Bleach
          2. Alkaline glutaraldehyde
          3. Ethylene oxide
  18. References
    1. Suntharam (2006) First 24 hours, Park Nicollet Lecture
    2. Jabbar (2003) Prim Care 30(1):63
    3. Kyne (2001) Gastroenterol Clin North Am 30(3):753
    4. Schroeder (2005) Am Fam Physician 71(5):921

Clostridium difficile (bacteria) (C0079134)

Definition (CSP)causes antibiotic-induced diarrhea or pseudomembranous colitis in humans; found in the colonic flora in 3% of healthy adults.
Definition (MSH)A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis (ENTEROCOLITIS, PSEUDOMEMBRANOUS) in patients receiving antibiotic therapy.
ConceptsBacterium (T007)
EnglishBacillus difficilis, Clostridium difficile, Clostridium difficilis
CreditsDerived from the NIH UMLS (Unified Medical Language System)



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