Clostridium difficile
At a Glance
Why Get Tested?
To detect the presence of Clostridium difficile toxin
When to Get Tested?
When a patient has mild to moderate non-bloody diarrhoea that persists for several days with abdominal pain, loss of appetite, and fever, following antibiotic therapy
Sample Required?
A fresh faecal sample that has not been contaminated with urine or water
Test Preparation Needed?
None
The Test Sample
What is being tested?
This test detects the presence of Clostridium difficile toxin A and/or B in a fresh or frozen faecal (stool) sample. C. difficile is a bacterium that is a part of the normal bacterial flora in the gastrointestinal tract of up to 65% of healthy infants but only of 3% of healthy adults. While C. difficile is frequently carried by infants, it does not usually cause diarrhoea in this young children. The risk of being affected increases with age and increases in those who are immunocompromised, have acute or chronic colon conditions, have been previously affected by C. difficile, or who have had recent gastrointestinal surgery, chemotherapy or gastric acid suppression.
C. difficile-associated diarrhoea usually develops in patients who have been taking antibiotics for several days, but it can also occur several weeks after treatment is completed. Broad-spectrum antibiotics can disrupt the balance of the normal intestinal flora when they are used to treat other infections. As the result, bacteria that are susceptible to the antibiotic will be eliminated from the gut and C. difficile that are resistant to the antibiotic will survive.
The C. difficile may produce two main toxins - toxin A and toxin B. The combination of an overgrowth of C. difficile and toxin production can damage the lining of the colon and lead to severe inflammation of the colon and prolonged diarrhoea. Dead tissue, fibrin, and numerous white blood cells can form a layer over the inflamed bowel, which is referred to as pseudomembranous colitis. C. difficile toxins are detected from stools of 15-25% of patients with antibiotic-associated diarrhoea and in stools of more than 95% of patients with pseudomembranous colitis.
C. difficile is the most common cause of diarrhoea in patients while hospitalised. Although community-acquired C. difficile is increasingly recognised, transmission in healthcare settings is the most common way of infection acquisition. Many patients may have C. difficile in their intestine on hospital admission without any specific symptoms, and it only becomes a problem after they are treated with antibiotics. C. difficile-associated disease ranges from mild diarrhoea to a more severe colitis, or to toxic megacolon, which can result in sepsis and death. Symptoms may include frequent loose stools, abdominal pain and cramps, nausea, fever, dehydration, fatigue, and leukocytosis. Treatment typically consists of stopping the original antibiotic and administering specific oral antibiotic therapy to which the C. difficile is susceptible. Most patients improve as the normal flora re-establishes itself, but relapses may occur usually within a week after completion of therapy. Multiple relapses have been reported.
Recently, a new, more dangerous variety of C. difficile, called ribotype 027 strain, has been implicated in hospital-acquired infection outbreaks in the Northern America and Europe, which have been associated with increased morbidity and mortality.
How is the sample collected for testing?
A fresh faecal (stool) sample is collected in a sterile container. The faecal sample should not be contaminated with urine or water. Once it has been collected, the faecal sample should be taken to the laboratory immediately or refrigerated and taken to the lab as soon as possible.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
The Test
How is it used?
The Clostridium difficile toxin test is used to diagnose ntibiotic-associated diarrhoea and pseudomembranous colitis that is caused by C. difficile. It may also be ordered to detect recurrent disease.
If the patient has a positive toxin test, the doctor will typically discontinue any antibiotics that the patient may be taking and prescribe an appropriate treatment of oral antibiotic, such as metronidazole or vancomycin, to eliminate the C. difficile bacteria.
When is it requested?
Early diagnosis is key to preventing complications from severe C. difficile infection as well as preventing transmission. A C. difficile toxin test may be ordered when a hospitalised patient has frequent loose stools, abdominal pain, fever and/or nausea during or following a course of antibiotics or following a recent gastrointestinal surgery. It may be ordered when an outpatient develops these symptoms within 6-8 weeks after taking antibiotics, several days after chemotherapy, or when a patient has a chronic gastrointestinal disorder that the doctor suspects is being worsened by a C. difficile infection. The C. difficile toxin test may be ordered to help diagnose the cause of frequent diarrhoea when no other discernable cause (such as parasites or pathogenic bacteria) has been detected.
If a patient treated for antibiotic-associated diarrhoea or colitis relapses and symptoms re-emerge, C. difficile toxin testing may be ordered to confirm the presence of the toxin.
What does the test result mean?
If the C.difficile toxin test is positive, it is likely that the patient’s diarrhoea and related symptoms are due to an overgrowth of toxin-producing C. difficile. Occasionally, false positives may be seen with grossly (visibly) bloody faecal samples.
If the test is negative but the diarrhoea continues, another sample needs to be tested. The rapid C. difficile toxin tests detect less than 85% of cases, so the toxin may have been missed the first time. Since the toxin breaks down at room temperature, a negative result may also indicate that the sample was not transported, stored, or processed promptly. A negative test result may also mean that the diarrhoea and other symptoms are being caused by something other than C. difficile.
Is there anything else I should know?
There is currently no single test that is both very accurate and rapid. There is a rapid test to detect a common antigen expressed by all strains of C. difficile, but it does not tell the doctor if the bacteria are producing the harmful toxins. An additional test to detect toxin A and B must be performed to confirm C. difficile-associated disease. The usual method to detect C. difficile toxin A and B is by a rapid enzyme immunoassay. Results are available after 1 to 4 hours, depending on the test. A cytotoxin test that looks for the toxic effects of stool on human cells grown in culture is a more sensitive method to detect toxin, but it requires 24 to 48 hours to get the result.
Clostridium difficile can be grown and isolated on a faecal culture, but its presence does not indicate whether the strain present is a toxin producer. It also does not distinguish between C. difficile colonisation and overgrowth/infection.
An endoscopic procedure can be used to diagnose C. difficile colitis. A specialist (gastroenterologist) can observe and take a biopsy sample from any characteristic pseudomembranous lesions that may be present.
Molecular testing methods, such as PCR are being investigated for use in the detection of the presence of C. difficile toxins. They are more sensitive than immunoassays, can pick up different types of toxin and epidemic varieties of this pathogen but are unable to distinguish between an active and past infection since traces of the toxin may be detected long after the patient has recovered.
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