College of American Pathologists
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Diagnosing Clostridium difficile diarrhea and colitis

September 2003

CAP TODAY published an article in November 2000 about Nancy Cornish, MD, director of microbiology, Methodist Hospital and Children’s Hospital, Omaha, who is working to improve physician test ordering. She teaches Methodist’s physicians about lab tests through periodic clinical briefs, which she writes and distributes. The response of CAP TODAY readers to Dr. Cornish’s work was so enthusiastic and the requests for copies of her briefs so numerous that we asked her to share the clinical briefs she writes as they become available. Here, this month, is her word on Clostridium difficile diarrhea and colitis.

Our laboratory policy for Clostridium difficile diarrhea and colitis says:

  • Only liquid stools—those that assume the shape of the container—will be accepted for testing.
  • Issue written reports, not phone results.
  • Only retest patients with a previously positive result after 14 days.

The diagnosis of C. difficile-associated disease initially should be suspected based on clinical findings. Most patients with the disease will present with two to three days of profuse watery diarrhea and exposure to antibiotics or antineoplastic agents, usually within eight weeks of presentation. Other symptoms may include fever and abdominal pain and tenderness.

A number of laboratory tests are available to aid diagnosis, including enzyme immunoassay for toxins A and B and a cytotoxin B tissue culture assay. The sensitivity of these tests ranges from 65 to 100 percent, and specificity ranges from 75 to 100 percent. The sensitivity and specificity are, in general, better for the tissue culture assay, but this assay is labor intensive, expensive, and takes up to two days to generate results. The EIA, in contrast, is faster and less expensive and generates results within one day.

The specificity of C. difficile toxin testing varies with the type of patient tested. Patients who do not meet the clinical criteria for C. difficile-associated disease may have a positive test result due to carriage of the organism. A number of studies of asymptomatic carriage rates have been performed in the following populations:

Children younger than two years7–60%
Cystic fibrosis patients=50%

Children older than two years<4%

Healthy adults<4%

Healthy adults given antibiotics=49%

Adults hospitalized more than four weeks 50%

Elderly in chronic care21%

Elderly in acute care14%

Asymptomatic carriage is approximately two- to five-fold more common than the disease itself. This makes it difficult to interpret lab test results if such a patient develops diarrhea from another source. The patient most at risk for C. difficile-associated disease is the hospitalized elderly person on antibiotics.

The Society for Healthcare Epidemiology of America and the Infectious Disease Society of America have published the following guidelines for diagnosing and treating patients with suspected C. difficile-associated disease.

Guidelines for use of the C.difficile toxin assay:

  • Test only diarrheal stool—that which assumes the shape of the container.
  • Do not perform tests of cure. (Cure is cessation of symptoms since the toxin tests can remain positive for long periods after treatment.)
  • Test only specimens from patients who are older than one year due to the high carriage rate in infants.
  • Test diarrhea that develops after three days of hospitalization for C. difficile. (Stool for culture and ova and parasites are not recommended because of the low yield. Other stool tests should be ordered as clinically indicated.)

Guidelines for management of diarrhea and colitis associated with C. difficile infection:

  • Discontinue the implicated antibiotic if possible. (Twenty to 25 percent of patients will respond to this alone.)
  • Use supportive measures.
  • Avoid use of antiperistaltic agents.
  • Follow infection control policies for hospitalized patients.
  • Treat with metronidazole orally for 10 days, 500 mg three times daily or 250 mg four times daily (children orally 30 mg/kg/day, four times daily), when diarrhea is severe; there is evidence of colitis; diarrhea persists despite discontinuing the implicated antibiotic; or it is necessary to continue treatment of the original infection with the implicated antibiotic. The drug can be administered intravenously if the patient can’t tolerate oral administration.
  • Treat with vancomycin orally for 10 days, 125 mg four times daily (children orally 40 mg/kg/day, four times daily), when the patient is pregnant; intolerant, allergic, or not responsive to metronidazole; or critically ill because of C. difficile-associated diarrhea or colitis.

If tests for C. difficile are negative and the patient has persistent symptoms:

  • Repeat the EIA A/B test.
  • Use an alternative test, such as cytotoxin B tissue culture.
  • Expand the diagnostic evaluation to include other causes.
  • Treat empirically for C. difficile disease.

If the patient fails to respond to metronidazole therapy and his or her tests remain negative, the patient probably does not have C. difficile-associated disease. Patients may on rare occasions present with an ileus without prior diarrhea. This may be secondary to antiperistaltic agents or opiates that were administered postoperatively. Making the diagnosis is difficult in these cases and may require endoscopy. An infectious disease or gastroenterology consult may aid diagnosis.

Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med. 2002;346:334–339.

Gerding DN, et al. Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995;16:459–477.

Spencer RC. Clinical impact and associated costs of Clostridium difficile-associated disease. J Antimicrob Chemother. 1998;41 (suppl C): 5–12.
To view Dr. Cornish’s other clinical briefs, go to and click on “Technical bulletins & micro briefs.”