Clostridium Difficile Diagnostic Guidelines Updated

New guidelines on the best practice methods to diagnose Clostridium difficile infection (CDI) have been released and the latest document updates the original 2009, and includes recommendations concerning the use of new diagnostic technology such as nucleic acid amplification tests (NAAT).

The main objectives of this update of the guidance document are to summarize the currently available evidence concerning laboratory diagnosis of CDI and to formulate and revise recommendations to optimize CDI testing. This update is essential to improve the diagnosis of CDI and to improve uniformity in CDI diagnosis for surveillance purposes among European countries.

Scientists working under the auspices of The European Society of Clinical Microbiology and Infectious Diseases (ESCMID, Basel, Switzerland) identified 795 new studies, of which 693 were excluded and 102 selected for review. Of these, a further 61 were excluded, leaving 41 studies to be taken forward and used to support the new guidelines. Reasons for exclusion included incorrect or inconsistent reference testing, incorrect or inconsistent index testing, incorrect sample storage and incomplete sample testing. A total of 43 studies were also considered from the original meta-analysis, of which 28 were excluded and 15 taken forward.

Various laboratory assays available from commercial suppliers were assessed for their ability to diagnose CDI accurately. A reference test, typically cell cytotoxicity neutralization assay (CNNA) or toxigenic culture (TC) was used to investigate the accuracy of several tests that have emerged since 2009. These included enzyme immunoassays (EIA) that detect glutamate dehydrogenase or toxins A and B, and the new NAATs.

The strongest recommendations based on the evidence from all studies in the meta-analysis were: Samples to be tested for CDI should not be limited to cases in which a physician has specifically recommended; a rectal swab can be used for testing by (toxigenic) culture, NAAT or glutamate dehydrogenase (GDH) EIA in patients with apparent ileus (inactive bowel with no discernable bowel sounds); single, standalone tests are not reliable and should not be used: a two-step algorithm is necessary.

This two-step algorithm involves a combination of fast assays with follow up tests: Route one – the two-stage procedure should begin with either an NAAT or GDH EIA test. Negative tests should be treated as CDI negative, while positive tests should be followed up with a toxin A/B EIA test to confirm the result. Route two – the two-stage procedure should begin with both the GDH EIA test and the toxin A/B EIA test. If both are positive, CDI is likely to be present. If both are negative, CDI is unlikely to be present, however if GDH is positive and toxin A/B is negative, then the tests may optionally be followed up with an NAAT or TC test.

E.J. Kuijper a professor of experimental microbiology and senior author of the study said, “The new guidelines are intended for use among medical microbiologists, gastroenterologists, infectious disease specialists and infection control practitioners. Our aim is to not only improve diagnosis of CDI, but also to standardize the diagnostic process across Europe to allow for improved surveillance of the disease.” The study was published online on July 22, 2016, in the journal Clinical Microbiology and Infection.

Related Links:
The European Society of Clinical Microbiology and Infectious Diseases