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 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) 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 (31%) than community-acquired infections (19%)

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

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 with lower abdominal cramps in most patients

• Physical examination normal, or mild left lower quadrant tenderness

• With more serious illness, abdominal pain, profuse watery diarrhea with up to 30 stools per day

• Stools may have mucus but seldom gross blood

• Usually low-grade fever (but may be elevated up to 40°C)

• Abdominal tenderness mild unless severe disease

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

• Mild disease: no or minimal leukocytosis

• Severe disease: leukocytosis as high as 50,000/mcL (50 × 10⁹/L)

• Fecal leukocytes in only 50%

• Pathogenic strains of C difficile produce toxins TcdA and TcdB

• Rapid enzyme immunoassays (EIA) for toxins TcdA and TcdB have a 75–90% sensitivity with one stool specimen, > 90–95% sensitivity with two specimens

• Nucleic acid amplification tests (eg, PCR assays)

  • Preferred over EIA

  • Amplify the toxin TcdB gene

  • Have ...