From the Guidelines
A patient who tests positive for toxin via PCR but negative for the toxin itself should not be treated for C. difficile infection (CDI) if they are asymptomatic, as the risk of infection control transmission is present but the patient does not require treatment, according to the most recent and highest quality study by Polage et al. 1. The significance of a patient testing positive for toxin via PCR but negative for the toxin itself lies in the distinction between colonization and active infection. PCR detects the presence of toxin genes, which may indicate colonization without active toxin production, whereas toxin detection via enzyme immunoassay (EIA) confirms the presence of toxin and active infection. Key points to consider in this scenario include:
- The patient's symptoms: asymptomatic patients are generally not treated, while symptomatic patients may require treatment regardless of toxin EIA results if PCR is positive and other causes of symptoms have been ruled out 1.
- The risk of infection control transmission: patients who are PCR positive but toxin negative may still pose an infection control risk, as they can shed the bacteria and transmit it to others 1.
- The use of a multistep algorithm for diagnosis: a diagnostic approach that includes a test that is more specific for CDI, such as a relatively sensitive toxin test, can help distinguish between colonization and active infection 1. The study by Polage et al. 1 found that patients who were toxin negative/PCR positive had a similar rate of CDI-related complications and mortality as patients who were negative by both tests, suggesting that treatment is not necessary for asymptomatic patients who are PCR positive but toxin negative. In terms of treatment, the study by Polage et al. 1 supports the use of a toxin EIA test, such as the Meridian Tox A/B test, to diagnose CDI, rather than relying solely on PCR results. Some important considerations when interpreting PCR and toxin EIA results include:
- The sensitivity and specificity of the tests: PCR is more sensitive but less specific for active disease, potentially detecting colonization without active infection 1.
- The clinical context: asymptomatic carriers (PCR positive without symptoms) generally do not require treatment, while symptomatic patients should be treated regardless of toxin EIA results if PCR is positive and other causes of symptoms have been ruled out 1.
From the Research
Significance of Positive Toxin PCR and Negative Toxin Test
- A patient testing positive for toxin via PCR (Polymerase Chain Reaction) but negative for the toxin itself may not necessarily require treatment, as the presence of the toxin gene does not always correlate with the production of the toxin 2.
- Studies have shown that patients with positive PCR results but negative toxin tests (Tox-/PCR+) have similar outcomes to those without C. difficile infection, including shorter duration of diarrhea and lower rates of CDI-related complications and deaths 2, 3.
- The use of molecular tests, such as PCR, for CDI diagnosis without tests for toxins or host response may lead to overdiagnosis, overtreatment, and increased healthcare costs 2.
- However, some studies suggest that toxin-negative patients diagnosed by PCR may still experience CDI-related complications, emphasizing the need for individualized clinical evaluation 4.
Clinical Implications
- The decision to treat a patient with a positive PCR result but negative toxin test should be based on clinical judgment, taking into account the patient's symptoms, medical history, and other diagnostic test results 3, 4.
- Patients with positive toxin tests are more likely to have severe-complicated forms of CDI and recurrences, and therefore may require more aggressive treatment 4.
- Further research is needed to fully understand the significance of positive toxin PCR and negative toxin test results, and to develop evidence-based guidelines for the diagnosis and treatment of CDI 5, 6.