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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 not attributable to Clostridioides difficile and are usually mild and self-limited

  • Symptoms of antibiotic-associated colitis vary from mild to fulminant almost all colitis is attributable to C difficile

  • Diagnosis is established by stool assay in most cases

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 3% of healthy adults and 8% of hospitalized patients

    • Releases two toxins: TcdA and TcdB

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

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

    • Is more prevalent among hospital-associated infections (31%) than community-acquired infections (19%)

    • Has been associated with outbreaks of severe disease with up to 7% mortality


  • Antibiotic-associated colitis is found in

    • Hospitalized or recently hospitalized patients

    • Elderly or debilitated patients

    • Patients with inflammatory bowel disease

    • Persons who have received

  • Multiple antibiotics or prolonged antibiotic therapy

  • Proton pump inhibitor therapy

  • Enteral tube feeding

  • Chemotherapy

Clinical Findings

Symptoms and Signs

  • Mild to moderate greenish, foul-smelling watery diarrhea with lower abdominal cramps in most patients

  • Physical examination normal, or mild left lower quadrant tenderness

  • Stools may have mucus but seldom gross blood

  • Fulminant disease

    • Occurs in up to 10 % of patients

    • Characterized by fever; hemodynamic instability; and abdominal distention, pain, and tenderness

    • Most patients have profuse diarrhea (up to 30 stools/day)

    • However, diarrhea may be absent or appear to be improving in fulminant disease due to ileus

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

  • Mild disease: no or minimal leukocytosis

  • Severe disease

    • White blood count > 30,000/mcL

    • Serum albumin < 2.5 g/dL (due to protein-losing enteropathy)

    • Elevated serum lactate

    • Rising serum creatinine

  • Rapid enzyme immunoassays (EIAs) detect the presence of C difficile toxins TcdA and TcdB ...

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