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A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Clostridium difficile

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Clostridium difficile is a Gram-positive, spore-forming, anaerobic bacillus that can cause pseudomembranous colitis. C. difficile-associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis. Risk factors for CDAD include antibiotic use within three months prior to symptom onset, and exposure to a health-care setting. Colonization with C. difficile is common in hospitalized patients (20-40%), while only 3% of healthy adults are colonized. Exposure to antibiotics is believed to alter the normal gut flora, resulting in overgrowth of C. difficile. Production of exotoxins A & B by the organism subsequently results in CDAD, and detection of toxin is the basis for diagnostic laboratory tests.



CDC data indicates that the incidence and severity of CDAD has increased since the year 2000. Two recent publications (NEJM 2005; 353:2433-2449) describe an apparently new, more virulent strain of C. difficile that has been responsible for hospital outbreaks in the U.S. and Quebec, Canada. This epidemic strain differs from common strains in that it produces 16 times more toxin A and 23 times more toxin B, which may result from a deletion in the negative regulator gene, tdC. The epidemic strain was also resistant to fluoroquinolones, and prior use of fluoroquinolones was identified in 52% of cases. More severe CDAD is associated with the epidemic strain, including more frequent toxic megacolon, leukemoid reaction, shock, and death, particularly in the elderly.

Equally alarming, community-acquired cases of severe CDAD in individuals with minimal risk factors have been reported recently (MMWR 2005;54:1201-1205). Analysis of the organism responsible for two of these infections showed they were not caused by the epidemic strain. Another report suggests that use of proton pump inhibitors increases the risk of community-acquired CDAD by 2-3 times (JAMA 2005; 294:2989-2995).

Hand hygiene is of particular importance in reducing the incidence of CDAD. Of note is that hand-washing with soap and water is necessary for C. difficile eradication, as its spores are resistant to alcohol-gel based preparations. In light of the apparent changing epidemiology of CDAD, the CDC has stressed the importance of judicious antibiotic use, and the need for a high index of suspicion for community-acquired CDAD in patient with severe diarrhea.

Common nonspecific laboratory abnormalities in patients with Clostridium difficile-associated disease (CDAD) include leukocytosis and hypoalbuminemia. Fecal leukocytes are detected in 50-60% of cases. Gram stains of fecal specimens are of no value, since C. difficile is only a small part of the fecal flora, even among patients with severe colitis. Likewise, anaerobic stool cultures are of little use in the diagnosis, due to the inability to distinguish between toxigenic and nontoxigenic strains.

The newest diagnostic tests for CDAD are enzyme immunoassays (EIA), which detect 100 to 1000 pg of cytotoxin A & B. The sensitivity and specificity of the test are 95% and 97% respectively. A positive test indicates the presence of Clostridium difficile. Normal stools are negative for toxins.

The following criteria should be followed before requesting this test;
  • the patient must have diarrhea
  • the history should suggest antibiotic-associated disease
  • babies less than 2 years old should not be tested routinely, since they have such high asymptomatic carrier rates (15-70%)
Specimen requirement is 20 mL of liquid stool collected in a screw-capped, sterile container. Refrigerate immediately after collection.