From the Guidelines
A positive C. difficile PCR test does not necessarily indicate an active infection, as it cannot distinguish between active infection and asymptomatic colonization. For a diagnosis of active C. difficile infection (CDI), the patient must have both a positive test and clinical symptoms, typically diarrhea (defined as 3 or more loose stools in 24 hours) 1. Many people, especially in healthcare settings, can be colonized with C. difficile without having an infection, with the prevalence of asymptomatic colonization ranging from 3-15% in healthy adults but as high as 50% in certain hospitalized populations 1. Therefore, testing should only be performed on patients with clinically significant diarrhea, and test results should always be interpreted in the context of the patient's clinical presentation 1. Some key points to consider in the diagnosis of CDI include:
- The diagnosis of CDI should be based on clinical signs and symptoms in combination with laboratory tests, with stool testing only performed on diarrheal stools from at-risk patients with clinically significant diarrhea 1.
- Nucleic acid amplification tests (NAATs) for C. difficile toxin genes appear to be sensitive and specific and may be used as a standard diagnostic test for CDI, but they cannot distinguish between colonization and active disease 1.
- Testing formed stools or using C. difficile tests as a "test of cure" after treatment is not recommended, as patients may continue to shed the organism for weeks after symptoms resolve 1. It is essential to consider the clinical context, including a history of recent antibiotic administration and residence in a hospital, when selecting patients for testing 1. The use of NAATs, such as real-time PCR (RT-PCR) assay and loop-mediated isothermal amplification (LAMP) assay, can provide accurate and efficient detection of C. difficile, but the results should be interpreted in the context of the patient's clinical presentation 1. In summary, a positive C. difficile PCR test should be interpreted with caution, considering the patient's clinical symptoms and presentation, to avoid overdiagnosis or underdiagnosis of CDI.
From the Research
Diagnosis of C. diff Infection
- A positive Clostridioides difficile (C. diff) Polymerase Chain Reaction (PCR) test does not necessarily indicate an active infection, as it can also detect colonization 2, 3.
- The PCR test is sensitive, but there are concerns about false-positive results, especially in populations with low rates of C. diff infection or in individuals with C. diff colonization 3, 4.
- A two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C. diff toxin is recommended to reduce the risk of false-positive results 2.
Clinical Presentation and Diagnosis
- The clinical presentation of C. diff infection ranges from diarrhea to fulminant infection, and diagnosis is based on direct detection of C. diff toxins in feces, often using a combination of tests 5.
- No single test is suitable as a stand-alone test confirming C. diff infection, and a positive PCR test should be interpreted in the context of clinical symptoms and other diagnostic results 5, 4.
Recurrence and Treatment
- Recurrence of C. diff infection is a common complication, and treatment options include antibiotics, fecal microbiota transplantation, and immunotherapy 2, 3, 6.
- The risk of recurrence is associated with factors such as age, antibiotic use, and severity of initial infection 6, 4.
- Treatment approaches, including the use of vancomycin, fidaxomicin, and metronidazole, are guided by the severity of the infection and the risk of recurrence 2, 3, 5.