Tests to detect Clostridium difficile (C. difficile) and its toxins are used to diagnose diarrhea and other conditions and complications caused by toxin-producing C. difficile. (See the "What is being tested?" section for more on these bacteria.) Conditions resulting from this bacterial infection include pseudomembranous colitis, in which dead tissue, fibrous protein, and numerous white blood cells form a lining over the surface of the inflamed bowel, toxic megacolon, and perforated bowel. Testing may also be ordered to detect recurrent disease.
There are a number of tests that are available to detect the infection and to determine if the strain that is present produces toxin. Some tests are very sensitive but take some days to complete, while other tests are rapid (several hours) but are not considered to be very sensitive or specific. The Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) have proposed a two-step testing process. This recommendation was part of a 2010 guideline that is currently (2014) under review. The two-step process includes:
Perform an initial screen on stool samples using a test for a C. difficileantigen called glutamate dehydrogenase (GDH). This test detects an antigen that is produced in high amounts by C. difficile, both toxin and non-toxin producing strains. It is considered to be very sensitive, but it is not very specific for toxin-producing C. difficile. This test indicates if C. difficile is present but not if the bacteria are producing toxins.
Follow up positive screening results with either of the following for confirmation and to detect the presence of toxins:
Cell cytotoxicity test is a tissue culture to detect the C. difficile toxin. It is a test that looks for the effects of the cytotoxin (cytotoxicity) on human cells grown in culture. It is a more sensitive method to detect toxin, but it requires 24 to 48 hours to get the test result.
Toxigenic stool culture, which requires growing the bacteria in a culture and a second step to detect the presence of the toxins, is a very sensitive test for C. difficile. It is still considered to be the gold standard. However, it can take 2 to 3 days for results. A culture will also not distinguish between C. difficilecolonization and overgrowth/infection. Further testing for the toxin must be performed.
PCR assays are rapid and very sensitive methods to confirm the presence of C. difficile toxin. However, they are expensive. Some laboratories screen samples with the GDH test and confirm only the positive samples with the molecular assay. Not all laboratories have the capability of performing molecular testing.
Other tests that may be used, sometimes in some combination with those listed above, include C. difficile toxin B, or toxins A and B, by enzyme immunoassay (EIA) tests. These were commonly used by laboratories and results are typically available within 1 to 4 hours. Though these tests are rapid and widely available, we now know that they are not sensitive enough to detect many infections; they miss up to 30% of cases. Therefore, they are not recommended for use by some professional organizations.
C. difficile testing may be ordered when a person hospitalized for more than three days has frequent watery stools, abdominal pain, fever, and/or nausea during or following a course of antibiotics or following a recent gastrointestinal surgery. Testing may be ordered for outpatients when someone develops these symptoms within 6-8 weeks after taking antibiotics, several days after chemotherapy, or when a person has a chronic gastrointestinal disorder that a health practitioner suspects is being worsened by a C. difficile infection. Tests for C. difficile may be ordered to help diagnose the cause of diarrhea when no other infectious or non-infectious causes have been detected.
When a person treated for antibiotic-associated diarrhea or colitis relapses and symptoms reoccur, C. difficile testing may be ordered to confirm the presence of the toxin. Testing should not be ordered to monitor the effectiveness of treatment or for those who are symptomatic. A subsiding of symptoms (diarrhea ceases and stools are formed) indicates a cure from infection. Repeat testing for C. difficile after a positive result is not advised and provides no useful clinical information. Molecular tests may remain positive for weeks after someone is cured and asymptomatic.
If tests for C. difficile and C. difficile toxin are positive, it is likely that the person's diarrhea and related symptoms are due to the presence of toxin-producing C. difficile.
A positive result for C. difficile bacteria or C. difficile antigen but a negative C. difficile toxin result means that the bacteria are present in the digestive tract but are not producing a detectable level of toxin.
Negative test results for both the bacteria and the toxin may mean that the diarrhea and other symptoms are being caused by something other than C. difficile. Since the toxin breaks down at room temperature within two hours, a negative result may also indicate that the sample was not transported, stored, or processed promptly. If there is a concern that a stool specimen has not been collected and processed properly, a second specimen may be submitted for testing after discussion with the laboratory.
If a person has positive C. difficile test results, the health practitioner will typically discontinue any antibiotics that the person is taking and prescribe an appropriate treatment of oral antibiotic, such as metronidazole or vancomycin, to eliminate the C. difficile bacteria. Recently, so-called stool transplants have been investigated as an effective treatment for people with recurrent C. difficile infections.
An endoscopic procedure can be used to diagnose C. difficile colitis. A specialist (gastroenterologist) can examine the colon and biopsy any characteristic pseudomembranous lesions that may be present.
This article was last reviewed on December 30, 2014. | This article was last modified on April 10, 2015.
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