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 two 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 U.S. 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 stools in patients without reassessment for the presence of diarrhea. Such repeat testing should be discouraged as it may lead to a greater risk of a false-positive result. 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. 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. 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.