A: Diagnostic testing for C. difficile should be performed only in patients with clinically significant diarrhea (patients with 3 or more loose stools in ≤24 hours) who have risk factors for CDI such as recent exposure to antibiotics, older age, and/or duration of stay at a hospital or nursing facility.1 Acceptable samples should be unformed stool specimens that take the shape of the container.

A: Molecular tests/NAATs are designed to detect DNA from Clostridium difficile organisms capable of producing toxin (also referred to as toxigenic C. difficile) found in stool. PCR is one type of NAAT. The sensitivity of detection of toxigenic C. difficile organism by GeneXpert has been reported to be 94–99%2-4 and correlated well with a clinical diagnosis of C. difficile infection (CDI).2 Commercially available molecular assays are not designed to assess host response or to determine if the patient requires treatment, although they do provide valuable information to the physician when used in the context of other clinical features. In addition, 80–90% of samples tested for C. difficile are negative. Because they are very sensitive, molecular tests can be used to “rule out” C. difficile in the majority of patients more confidently than with immunologic methods. Thus, a rapid and sensitive molecular test can help to avoid unnecessary empiric therapy that is often administered to patients during the time clinicians are waiting for lab results (as described below).

A: The first step is to determine if the patient’s sample contains toxigenic C. difficile. Patients positive for toxigenic C. difficile constitute an infection control risk, and can transmit disease to other patients.5,6 Once a patient with toxigenic C. difficile has been identified and appropriate infection control measures have been implemented, the next step is to determine if the patient has CDI and requires treatment. A number of features can be used to determine the presence of infection including the clinical picture (antibiotic history, frequency/severity of diarrhea) as well as other indicators of disease severity (for example, WBC count, creatinine level, albumin level, fever etc). Free toxin has also been evaluated as an indicator of infection.6,7 Guidelines advise that since enzyme immunoassay (EIA) tests for toxin A and B are less sensitive than other methods, such as PCR, they are not recommended for standalone use.1,8 A recent study by Polage et al. showed that the toxin assay failed to detect toxin in 30% of PCR-positive samples, as detected by cell cytotoxin assay repeat testing.6 In fact, among stool samples initially positive by PCR and negative for toxin that were sent for retesting (likely because the physician still suspected CDI), 21% of the toxin assays were positive upon retest. In lieu of definitive measure of disease, clinicians must take into account the complete clinical picture. As a recent editorial stated, “Regardless of which assay is used, it is best to remember to treat the patient, not the test.”