CDC Commentary: Testing for Clostridium difficile Infection

As part of CDC's Expert Commentary Series on Medscape, Dr. Carolyn Gould, a medical officer with the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention, takes a close look at important laboratory testing methods for Clostridium difficile infection (CDI). She also reviews which patients should be tested for CDI, the pros and cons of different testing methods, and why repeat testing during a single episode of diarrhea is discouraged.

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CDC Commentary: Testing for Clostridium difficile Infection
Carolyn Gould, MD, MSCR

Authors and Disclosures

Posted: 08/16/2010
Hello, my name is Dr. Carolyn Gould. I'm a medical officer in the Division of Healthcare Quality Promotion at CDC, and I'm happy to speak with you today as part of the CDC Expert Video Commentary Series on Medscape. In this video commentary, I'd like to address laboratory testing for Clostridium difficile infection, or CDI. I'll be discussing which patients should be tested for CDI, the pros and cons of different testing methods, and why repeat testing during a single episode of diarrhea is discouraged.

C difficile is a spore-forming, Gram-positive anaerobic bacillus that produces 2 exotoxins, toxin A and toxin B, which cause damage to the large intestine, resulting in diarrhea among infected patients. While C difficile is the most commonly recognized cause of antibiotic-associated diarrhea, it accounts for only 15%-25% of all such diarrheal episodes. The likelihood of a patient having CDI is increased if the patient has received antibiotics in the previous 8-12 weeks, is over 65 years of age, and has 3 or more diarrheal stools in a 24-hour period. Because patients who have received antibiotics or have recently recovered from CDI may be colonized without any symptoms, it is important that only diarrheal stools -- in other words, those stools that take the shape of the container they are in -- be tested for CDI.

In any case, reliable testing for CDI remains challenging. At this time the most common testing method for CDI in US hospitals is the enzyme immunoassay (or EIA) to detect toxins A and B in the stool. Although these tests provide results rapidly and are easily performed, the sensitivity of the commercially available EIAs is relatively low. Despite the high specificity of these assays, clinicians are often aware of their poor sensitivity, resulting in routine ordering of multiple stool tests in patients without reassessment for the presence of diarrhea. Such repeat testing should be discouraged as it may lead to a greater risk for a false-positive result.[1] Therefore, repeat testing should be based on whether the patient is still having diarrhea, and, if possible, a more sensitive testing method should be used. Remember that if there is a high suspicion of CDI, empiric treatment may be warranted to avoid delays in therapy.

The tissue cytotoxin assay, which also tests for free toxin in the stool, is generally more sensitive than the EIAs and was historically viewed as the gold standard test for the diagnosis of CDI.[2] However, the tissue cytotoxin assay is more difficult to perform than the EIA and has a relatively slow turnaround time, which limits its usefulness in the clinical setting. When using either an EIA or the tissue cytotoxin assay, it is important that stools be either transported to the laboratory within 2 hours or refrigerated because the toxin degrades rapidly at room temperature.

Recently, the toxigenic culture, in which stool is cultured for C difficile and a toxin assay is performed on any isolate to determine whether it is toxin producing, has become the new gold standard against which to compare the sensitivity and specificity of other tests. The main limitation of the toxigenic culture is that it is labor intensive and can have a very slow turnaround time. However, there are now other approved, rapid methods that approach the sensitivity and specificity of toxigenic culture in diagnosing CDI. These include the use of polymerase chain reaction (or PCR) tests to detect toxin-producing C difficile or 2-step testing paradigms that use the highly sensitive but nonspecific antigen EIA with confirmatory testing of positive results.[3,4]

Healthcare facilities should consider moving toward the use of more sensitive testing methods as a means of quickly and reliably identifying patients with CDI. This will allow for more rapid implementation of isolation precautions to prevent transmission as well as prompt initiation of therapy to improve patient outcomes. However, with more sensitive testing, it is even more important to ensure that only patients with active diarrhea are being tested; otherwise, the tests are more likely to detect asymptomatic colonization. Currently, there are no recommendations for active surveillance testing or isolating asymptomatic patients on the basis of their being colonized with C difficile. Moreover, patients who have recovered from CDI will often remain colonized for a prolonged period, and therefore repeat testing of patients to prove cure should be discouraged.

Given that both the incidence and severity of CDI have increased over the past several years, it is important that clinicians become more aware of how to recognize, diagnose, treat, and prevent CDI. The bottom line? Suspect CDI in patients who have received antibiotics in the previous 8-12 weeks and have had 3 or more diarrheal stools in a 24-hour period. For testing, the current gold standard is a toxigenic culture, but turnaround time is slow. For clinical laboratories, rapid tests that approach the sensitivity and specificity of toxigenic culture include PCR tests or 2-step testing paradigms that use rapid antigen assays with confirmatory testing.

We at CDC hope that this brief overview of the laboratory diagnosis of CDI and how it can be optimized to aid in both prevention and treatment has been helpful. For further information on the prevention of CDI and other healthcare-associated infections, visit the Web resources listed on this page. Thank you for watching.

Web Resources

SHEA/IDSA Guideline. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA)

CDC. Overview of Clostridium difficile Infections

CDC. Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006

Carolyn Gould, MD, MSCR is a Medical Epidemiologist in the Division of Healthcare Quality Promotion (DHQP) at the Centers for Disease Control and Prevention (CDC). She received her undergraduate degree at Harvard University and her medical degree at the University of Pennsylvania School of Medicine. She completed a residency in Internal Medicine and fellowship in Infectious Diseases at the University of Pennsylvania. After joining the faculty at Emory University in 2003, she served as Associate Hospital Epidemiologist and Co-Director of the Antimicrobial Management Program at Emory Crawford Long Hospital. Dr. Gould joined the CDC and the Commissioned Corps of the US Public Health Service in December 2006. Her primary roles involve responding to and preventing healthcare-associated infectious diseases. She is the primary author of the updated 2009 CDC/HICPAC Guideline for Prevention of Catheter-associated Urinary Tract Infections and is involved in a number of C difficile prevention initiatives.


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CDC Commentary: Testing for Clostridium difficile Infection

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