Colitis, Antibiotic-Associated

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

Demographics

• 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

Diagnosis

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 ...