From the Guidelines
An indeterminate Clostridioides difficile (C. diff) test result means that the diagnostic test has yielded results that are neither clearly positive nor negative, and clinical symptoms should guide management decisions. When a test result is indeterminate, healthcare providers should consider retesting the patient using a different method, such as a toxin enzyme immunoassay (EIA), which detects the actual toxins produced by C. diff that cause disease 1. This is because nucleic acid amplification tests (NAATs) that detect the presence of C. diff DNA cannot distinguish between active infection and colonization, and may yield indeterminate results 1. Some key points to consider in the management of indeterminate C. diff test results include:
- Clinical symptoms, such as diarrhea (3 or more loose stools in 24 hours), should guide management decisions, as patients with symptoms and an indeterminate result may need treatment, while those without symptoms typically don't require antibiotics 1.
- Retesting should not be performed routinely, but rather in cases where there are clear changes to the clinical presentation of suspected CDI, or in epidemic settings where CDI acquisition is more frequent 1.
- Common treatments for confirmed C. diff include oral vancomycin (125 mg four times daily for 10 days), fidaxomicin (200 mg twice daily for 10 days), or metronidazole (500 mg three times daily for 10 days) in mild cases 1.
- Indeterminate results occur because C. diff can be present in the gut without causing disease, making it important to correlate test results with clinical presentation before initiating treatment 1. It is also important to note that repeat testing to establish cure is not necessary, as >60% of patients may remain C. difficile positive even after successful treatment 1. In addition, empiric treatment without confirmatory testing of suspected recurrence is discouraged, as this may be unnecessary and indeed possibly harmful to microbiome restoration 1. Overall, the management of indeterminate C. diff test results requires a thoughtful and individualized approach, taking into account the patient's clinical symptoms, medical history, and the results of diagnostic testing 1.
From the Research
Definition of Indeterminate Test Result
An indeterminate Clostridioides difficile (C. diff) test result refers to a test outcome that cannot be classified as either positive or negative, often due to the presence of conflicting or inconclusive results from different testing methods.
Causes of Indeterminate Results
- The use of different testing methods, such as enzyme immunoassay (EIA) and nucleic acid amplification tests, can lead to conflicting results 2
- The presence of asymptomatic C. difficile colonization can result in overreporting of C. difficile infection (CDI) cases 3
- The limitations of current testing methods, including the lack of a standardized method for culture performance, can contribute to indeterminate results 2, 4
Clinical Implications
- Indeterminate test results can make it challenging to determine the appropriate course of treatment for patients with suspected CDI 5
- The use of clinical algorithms and multiple testing methods can help to improve the accuracy of CDI diagnosis and reduce the number of indeterminate results 6
- Clinicians should carefully evaluate the clinical correlates of indeterminate test results to determine the best course of action for patient management 4
Testing Methods
- Nucleic acid amplification tests are considered the most sensitive methods for detecting C. difficile in stool, but may have lower specificity than other testing methods 2, 6
- Toxin enzyme immunoassays are less sensitive than nucleic acid amplification tests, but may be better predictors of disease in certain patient populations 6
- The use of a two-step approach, beginning with a test for glutamate dehydrogenase (GDH) followed by a toxin test and/or a nucleic acid test, is recommended by some professional societies 6