CONTINUING EDUCATION :: C DIFFICILE
Figure 1. Distinguishing between carriers of C. difficile and patients with CDI can be challenging
predictive values (PPV) and fewer false positive results. PPVs are affected by the prevalence of the disease in the patient popula- tion being tested. The PPVs approaching >95% with some of the better performing toxin immunoassays have been reported from healthcare facilities with prevalence rates of 5% to 15%. The lower sensitivity of toxin immunoassays, compared to the picogram amounts detected by CCNA, has raised concerns about false negative results.2
(See Figure 2)=
GDH Immunoassays GDH immunoassays detect glutamate dehydrogenase, a metabolic enzyme produced by C. difficile. GDH is an excellent biomarker for C. difficile because it is a stable enzyme produced when the organism is actively growing in the large intestine. GDH consists of six identical subunits, thus providing mul- tiple repeating epitopes for increased binding of antibodies and better signal-to-noise ratios in immunoassays. As a result, GDH immunoassays are very sensitive with values comparable to those reported for NAAT assays for detecting the organism in fecal specimens. The high sensitivity results in high negative predictive values (NPV), and a negative GDH result accurately rules out CDI. GDH immunoassays do not differentiate between toxigenic and nontoxigenic strains. This is a limitation because nontoxigenic strains form spores and can spread in hospitals, although they are considerably less prevalent than toxigenic strains. Nontoxigenic strains do not carry the toxin genes and
do not cause disease. In fact, they may be protective by out- competing toxigenic strains in the intestine. A positive GDH result should be followed by a toxin assay when performing laboratory testing for CDI.
NAAT Assays NAAT assays detect the toxins A and B genes (tcdA and tcdB), which are located on a large 19.6 kilobase pathogenicity locus called the PaLoc. The tests use PCR or isothermal amplification for detection. Most of the tests target tcdB although some target tcdA or both genes. A positive result confirms the presence of a toxigenic strain but does not confirm the presence of toxin. Many of the NAAT assays now available are very sensitive, detecting fewer than 50 cells per gram feces. The high sensitivity results in high NPV, and a negative NAAT result accurately rules out CDI. However, the exquisite sensitivity of the tests leads to overdiagnosis and overcalls patients who are carriers. NAAT assays will give positive results with spores and dead cells which do not cause active CDI.
Algorithm testing is recommended C. difficile testing guidelines from the European Society of Clinical Microbiology and Infectious Disease (ESCMID), the Infectious Disease Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA), and the American Society of Microbiology (ASM) have been in place for several
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