Study presented at ASM Microbe 2025 questions the clinical value of adding enzyme immunoassays to PCR-based CDI diagnostics amid sensitivity concerns.
Clostridium difficile bacterium
Image credits: Unsplash
Presented at ASM Microbe 2025, a process improvement project led by Navarathna et al at Central Texas Veterans Health Care System evaluated the impact of incorporating enzyme immunoassays (EIA) into existing PCR-based diagnostic protocols for Clostridioides difficile infection (CDI).
The study compared two EIA platforms against PCR results and found that EIAs were less than 30% as sensitive as PCR. Out of 13 healthcare-onset CDI (HO-CDI) cases identified during the project, only 3 were confirmed by EIA. Interestingly, 5 inpatients who tested PCR positive but did not meet testing criteria had positive EIA results, indicating potential active infection. Lower PCR cycle threshold (CT) values, indicating higher bacterial loads, were significantly associated with EIA positivity, reinforcing the concept that EIAs require a higher level of toxin for detection.
PCR-based CDI testing is highly sensitive but may overdiagnose colonization rather than true infection.
EIAs are significantly less sensitive and may miss toxin-negative CDI cases when used as confirmatory tests.
Adding EIA to PCR testing may reduce reported HO-CDI but offers limited clinical value in managing patient care.
PCR testing has become the dominant method in the US due to its high sensitivity, which has also correlated with increased reporting of HO-CDI cases. Although, this sensitivity may lead to overdiagnosis by detecting asymptomatic colonization rather than active infection. To counter this, some centers have adopted a two-step algorithm adding EIA testing after a positive PCR or glutamate dehydrogenase (GDH) screen to improve specificity.
The authors concluded that while multi-step testing algorithms might reduce HO-CDI event rates by limiting overdiagnosis, they risk missing toxin-negative CDI cases due to EIA insensitivity. Consequently, the added EIA step may provide limited clinical utility for guiding CDI management decisions.
