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Key Features

Essentials of Diagnosis

  • Most cases of antibiotic-associated diarrhea are attributable to Clostridium 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

  • 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 a 97% sensitivity

    • Able to detect the NAP1 hypervirulent strain

  • Glutamate dehydrogenase (a common C difficile antigen) assay

    • Has a high sensitivity and negative predictive value ...

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