Understanding Discordant Results in C. difficile Testing

Causes of Discordant Results

Discordant results in C. difficile infection testing typically occur in two-step testing algorithms when the first test is positive but the second test is negative, creating uncertainty about whether the patient has active CDI or is simply colonized with C. difficile without active infection 1, 2
Two-step testing approaches inherently generate discrepant results due to differences in what each test detects, such as organism presence vs. toxin production, in patients with suspected CDI 1

When patients test positive for C. difficile organism but negative for toxins, CDI cannot be differentiated from asymptomatic colonization, highlighting the need for improved diagnostic methods and access to reference tests in symptomatic patients 2, 3
Patients with discordant results may have different clinical outcomes than those with concordant positive results, emphasizing the importance of clinical correlation in diagnosis and management 4

The European Society of Clinical Microbiology and Infectious Diseases recommends that interpretation of C. difficile laboratory results should be done in the clinical context, considering the background prevalence of C. difficile in the institution, to guide patient management and infection control 2
Discordant results emphasize the importance of clinical correlation, with diagnosis based on clinical signs and symptoms in combination with laboratory tests, in patients with suspected CDI 6

A two-step protocol is recommended for CDI testing, with the first step using GDH, toxin EIA, or molecular test for TcdB, and the second step using a method to detect free fecal toxins or GDH/toxin genes, in symptomatic patients with clinically significant diarrhea 2
Testing should only be performed on unformed stools from symptomatic patients with clinically significant diarrhea and no obvious alternative explanation, according to the World Journal of Emergency Surgery guidelines 6, 7

Clinical assessment remains crucial, with patients managed based on symptom severity, risk factors, and overall clinical presentation, in the presence of discordant results 1
Isolation of patients with suspected CDI should be implemented promptly to limit C. difficile transmission, even before confirmatory testing is complete, as recommended by the Clinical Microbiology and Infection guidelines 1