From the Guidelines
A positive Clostridioides difficile (C. diff) Polymerase Chain Reaction (PCR) result with a negative Enzyme Immunoassay (EIA) result does not necessarily indicate active infection, as it may represent colonization rather than active disease. This is because PCR tests detect the presence of C. difficile DNA, specifically genes that encode toxins, but cannot distinguish between colonization and active infection 1. The EIA test, on the other hand, specifically detects the actual toxins produced by C. difficile that cause disease. When the EIA is negative, it suggests the organism is present (detected by PCR) but not actively producing toxins that cause symptoms.
Clinical Assessment and Diagnosis
Clinical assessment is crucial in this scenario, as patients with symptoms like diarrhea (3+ loose stools in 24 hours), abdominal pain, and fever without other explanations may still require treatment despite the negative EIA result 1. However, in asymptomatic patients, treatment is not recommended as it does not improve outcomes and contributes to antibiotic resistance. This discrepancy occurs because approximately 3-5% of healthy adults and up to 50% of hospitalized patients can be colonized with C. difficile without having active disease.
Diagnostic Test Methods
The choice of diagnostic test method is also important, as a highly sensitive test such as a NAAT (nucleic acid amplification test) alone or a multi-step algorithm (e.g., GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) may be best for patients who are screened carefully for clinical symptoms likely associated with CDI 1. A 2- or 3-stage approach can increase the positive predictive value (PPV) compared to one-stage testing.
Key Considerations
- Clinical assessment is crucial in determining the need for treatment, even with a positive PCR result and negative EIA result.
- Asymptomatic patients with a positive PCR result and negative EIA result do not require treatment.
- The choice of diagnostic test method should be based on the patient's clinical symptoms and the pretest probability of CDI.
- A multi-step algorithm can increase the PPV and improve diagnostic accuracy.
- The study by Berry et al 1 provides evidence that PCR is more sensitive than CCNA and GDH, and that clinical diagnosis is a reliable reference standard for evaluating diagnostic test performance.
From the Research
Diagnostic Considerations
- A positive Clostridioides difficile (C. diff) Polymerase Chain Reaction (PCR) result indicates the presence of the bacteria's genetic material in a patient's stool sample 2.
- However, a positive PCR result does not necessarily confirm an active infection, as it can also detect colonization with C. diff 3.
- The diagnosis of C. diff infection (CDI) typically involves a two-step algorithm, with demonstration of the pathogen by means of its enzyme glutamate dehydrogenase by immunoassay and subsequent PCR of its toxin 2.
Relationship between PCR and Enzyme Immunoassay (EIA) results
- A negative Enzyme Immunoassay (EIA) result does not rule out the possibility of an active C. diff infection, as EIA tests may not detect all cases of CDI 4, 2.
- In one case report, a patient with a positive PCR result and a negative EIA result was successfully treated with fecal microbiota transplantation (FMT) for severe, refractory C. diff colitis 4.
Clinical Implications
- The presence of a positive PCR result in a patient with a negative EIA result should be interpreted in the context of the patient's clinical symptoms and medical history 2, 3.
- Further testing and evaluation may be necessary to determine whether the patient has an active C. diff infection or colonization with the bacteria 2, 3.
- Treatment decisions should be based on a comprehensive assessment of the patient's condition, including the results of diagnostic tests, clinical symptoms, and medical history 5, 2.