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For further information, see CMDT Part 15-34: Antibiotic-Associated Colitis

Key Features

Essentials of Diagnosis

  • Most cases of antibiotic-associated diarrhea are attributable to Clostridioides difficile and are usually mild and self-limited

  • Symptoms vary from mild to fulminant

  • In most cases, diagnosis is established by stool assay

General Considerations

  • Antibiotic-associated diarrhea is common

    • Characteristically occurs during antibiotic exposure, is dose-related, and resolves spontaneously after discontinuation

    • Most cases of diarrhea are mild and self-limited and do not require evaluation or treatment

  • Antibiotic-associated colitis is almost always caused by C difficile

    • Colonizes the colon of 4–15% of healthy adults and up to 21% of hospitalized adults and 15–30% of residents in long-term care facilities

    • Releases two toxins: TcdA and TcdB

    • C difficile is the major cause of diarrhea in patients hospitalized for > 3 days, affecting 15 of every 1000 patients

    • C difficile–induced colitis most commonly develops after use of ampicillin, clindamycin, fluoroquinolones, and third-generation cephalosporins

    • Symptoms begin during or shortly after antibiotic therapy but may be delayed for up to 8 weeks

  • A more virulent strain of C difficile (NAP1) has emerged

    • Contains an 18-base pair deletion of the TcdC inhibitory gene, resulting in higher toxin TcdA and TcdB production

    • More prevalent among hospital-associated infections

    • Associated with outbreaks of severe disease but appears to be declining in incidence


  • Hospitalized or recently hospitalized patients

  • Elderly or debilitated patients

  • Persons who have received

    • Multiple antibiotics or prolonged antibiotic therapy

    • Proton pump inhibitor therapy

    • Enteral tube feeding

    • Chemotherapy

  • Persons with inflammatory bowel disease

Clinical Findings

Symptoms and Signs

  • Mild to moderate greenish, foul-smelling watery diarrhea 3–15 times per day with lower abdominal cramps in most patients

  • Physical examination normal, or mild left lower quadrant tenderness

  • Stools may have mucus but seldom gross blood

  • Fever is uncommon

  • Abdominal tenderness mild unless severe disease

  • Fulminant disease in up to 10% of patients and characterized by

    • Hypotension or shock

    • Ileus

    • Megacolon

Differential Diagnosis

  • Antibiotic-associated diarrhea (not related to C difficile)

  • Other drug reaction

  • Diarrhea due to enteral tube feedings

  • Ischemic colitis

  • Other bacterial diarrhea

  • Inflammatory bowel disease

  • Rarely, other organisms (staphylococci, Clostridium perfringens) are associated with pseudomembranous colitis

  • Klebsiella oxytoca may cause a distinct form of antibiotic-associated hemorrhagic colitis


Laboratory Tests

  • Stool studies

    • Glutamate dehydrogenase assay

      • Has a high sensitivity and negative predictive value (> 95%)

      • Negative assay effectively excludes C difficile infection

      • Does not distinguish active infection from colonization

    • PCR tests

      • Amplify the toxin TcdB gene

      • Have a 97–99% sensitivity

      • Able to detect the NAP1 hypervirulent strain

      • Cannot distinguish active infection from colonization

    • Rapid enzyme immunoassays (EIAs)

      • Have a 75–90% sensitivity with one stool specimen

      • May be used as ...

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