Clostridium difficile Guidelines Address Testing Strategies

One component of the updated guidelines recommends changes in the types of laboratory tests used and the way that testing is performed in order to improve detection of C. difficile infections in a more timely manner. Previously, enzyme immunoassay (EIA) tests for the toxins produced by C. difficile were recommended as an acceptable alternative to a cell cytotoxin assay; however, new data have shown EIA tests to be much less sensitive, and they are now considered to be a suboptimal approach for diagnosis. In the 1995 recommendations, use of a latex test to detect a common enzyme produced by C. difficile, glutamate dehydrogenase (GDH), was discouraged. In the 2010 guidance, the organizations suggest use of a two-step process, which includes an initial screening of stool samples with an immunoassay test for GDH, a sensitive test for the presence of C. difficile bacteria, followed by a second, specific test to determine if the toxin that causes damage to the colon is present, since not all C. difficile may produce the toxin.

The new guidelines affirm that testing for C. difficile via culture is currently the most sensitive method, but this is a time-consuming process that requires 24 to 48 hours and is not clinically practical. The immunoassay test that detects the toxin produced by C. difficile is faster but is less sensitive and misses about 30% of infections. Most experts consider them inadequate, but more than 90% of U.S. labs use commercial versions of this method. The new guidelines could serve to steer labs toward using the more effective and efficient two-step testing strategy with a goal of improving the care of patients with this infection.

C. difficile infections are the most common cause of diarrhea while hospitalized. The illness may occur after people take antibiotic medications, which can reduce the beneficial bacteria in the gut that normally keep C. difficile in check. Overgrowth of toxin-producing C. difficile can result in persistent diarrhea, abdominal pain, loss of appetite, and fever. In more serious cases, prolonged diarrhea can cause severe intestinal inflammation and damage to the colon.

In recent years, CDIs have become more frequent, more severe, and more difficult to treat. Each year, there are 500,000 infections resulting in 30,000 deaths in the United States from C. difficile, with the highest mortality rate in those 65 or older. CDIs may cause severe and debilitating illnesses and present a significant financial burden to the healthcare system, costing U.S. healthcare facilities an estimated $3.2 billion per year. Despite these developments, tests that are available to detect the bacteria and/or its toxin have changed little from 1995. The new guidelines recognize the challenges presented with testing for C. difficile but encourage labs to use the newly recommended two-step screening and toxin-detecting process until improved tests that are faster and more sensitive become available. Even so, this recommendation is considered interim because the sensitivity of the test for GDH can vary with the kit being used. Other recommendations discussed in the new guidelines include:

• Testing should be done on unformed stool.
• Testing in asymptomatic patients is not clinically useful and is not recommended.
• Repeat testing within the same episode of diarrheal symptoms should be discouraged.

Testing via polymerase chain reaction (PCR) to detect the genes responsible for the C. difficile toxins may ultimately provide a more rapid, sensitive, and specific test. The guidelines note that additional studies are needed to evaluate it as an option. With increasing incidence of C. difficile and more virulent strains, development of a faster, more sensitive method of testing is needed that all clinical laboratories can perform at a reasonable cost to the patient.

Richard T. Ellison III, MD. New Guidelines on Clostridium difficile Disease in Adults. Journal Watch Infectious Diseases. Available online at http://infectious-diseases.jwatch.org. Posted April 14, 2010.

Press release. Infectious Disease Experts Release New Guidelines for Diagnosing, Managing, and Treating Clostridium Difficile (CDI). Epidemiology of America and the Infectious Diseases and the Society of America. Available online at http://www.idsociety.org/Content.aspx?id=16257 through http://www.idsociety.org. Issued March 22, 2010. Accessed May 3, 2010.

(September 2007) Redelings M, et. al. Increase in Clostridium difficile–related Mortality Rates, United States, 1999–2004. Emerging Infectious Diseases Vol. 13, No. 9. Available online at http://www.cdc.gov/eid/content/13/9/1417.htm through http://www.cdc.gov. Accessed June 1, 2010.

Gerding D, et. al. Clostridium difficile-associated Diarrhea and Colitis. Infection Control and Hospital Epidemiology (1995) Pg 459. PDF available for download at http://www.shea-online.org/Assets/files/position_papers/Cldiff95.PDF through http://www.shea-online.org.