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The page below is a sample from the LabCE course Clostridium difficile Infection (CDI): Overview, Laboratory Tests and Updated Guidelines.. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Laboratory Methods: Diagnostic Approach

The diagnosis of CDI usually begins with an examination of the symptoms and review of the risk factors for the patient. CDI should be suspected in a patient with acute diarrhea (> 3 loose stools in 24 hours) with no obvious explanation for the diarrhea especially with risk factors (recent antibiotic use, hospitalization, and advanced age).

For patients with clinically-significant diarrhea suspected of having CDI, liquid stool should be tested for C diff. Usually testing for C diff is unnecessary if there is no diarrhea or watery stools (a formed stool from asymptomatic patients should not be submitted for laboratory testing). The diagnosis of CDI is usually established when there is a positive laboratory test result for the toxins A or B (EIA testing) or the toxin B or A gene (NAAT assay).
For suspected recurrent CDI, the diagnostic approach is usually the same as the approach for an initial infection.
Most health care facilities and clinicians tend to favor the diagnostic approach of using a combination of laboratory testing to rapidly and accurately diagnose CDI. For example, many will favor the use of the EIA tests for GDH antigen and toxins A and B as the initial screening for CDI. A positive test for both GDH antigen and toxins A and B suggest a positive CDI. If both tests for GDH antigen and toxins A and B are negative, a negative CDI is suspected. If the initial EIA screening for GDH antigen and toxins A and B are discordant, then a confirmatory NAAT assay may be used. Because of the association with over-diagnosis and over-treatment, the NAAT test alone is usually not performed.
Repeat laboratory testing within seven days of the same episode of diarrhea is usually not indicated. Moreover, there is usually no need for laboratory testing in asymptomatic patients or in patients being treated for CDI (stool assays may remain positive for C diff during or after recovery).
In 2018, several professional organizations issued updated guidelines on laboratory testing to help improve the accuracy and rapidity of the diagnosis of CDI (a later section of this course will describe these updated guidelines and recommendations).