Laboratory Diagnostic Methods for Clostridioides difficile Infection: the First Systematic Review and Meta-analysis in Korea

Abstract

Background Various methods are used for the diagnosis of Clostridioides difficile infection (CDI). We systematically analyzed and investigated the performance of current laboratory diagnostic methods for CDI. Methods We performed systematic review and meta-analysis of studies in PubMed, Web of Science, Cochrane Library, and KoreaMed. The following methods were evaluated glutamate dehydrogenase (GDH) enzyme immunoassays (GDH EIAs), toxin A and B detection by enzyme immunoassays (toxin AB EIAs), and nucleic acid amplification tests (NAATs) for C. difficile toxin genes. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each method were calculated. Results Based on 39 studies, the pooled sensitivities/specificities were 92.7%/94.6%, 57.9%/97.0%, and 90.0%/95.8% for GDH EIAs, toxin AB EIAs, and NAATs, respectively, compared with those of toxigenic culture. The pooled sensitivities of automated EIAs were significantly higher than those of non-automated EIAs for both GDH and toxins A and B. The pooled sensitivity of Xpert C. difficile was significantly higher than those of other NAATs. PPVs increased as CDI prevalence increased, and NPVs were excellent when CDI prevalence was low; at CDI prevalence of 5%, PPV = 37%-65% and NPV = 97%-100%; at CDI prevalence of 50%, PPV = 92%-97% and NPV = 65%-98%. Conclusions Toxin AB EIAs still show unsatisfactory sensitivity, whereas GDH EIAs and NAATs show relatively high sensitivity. However, toxin AB EIAs are the most specific tests. This study may provide useful information for CDI diagnosis.

Nationwide Survey for Current Status of Laboratory Diagnosis of Clostridioides difficile Infection in Korea

“… 10 The perception of sensitivity and specificity of NAAT was mostly positive, suggesting that the specialists were quite satisfied, consistent with the fact that sensitivity and specificity of NAAT are known to be remarkable. 5 10 The relatively lower specificity of C. difficile culture encountered by some could be due to the characteristics of the culture containing non-specific bacteria with a specificity of 60–80%. Perceptions on the sensitivity of GDH was relatively positive, which was lower than NAAT but higher than toxin AB EIA, and that on the specificity led to lower satisfaction compared to NAAT and toxin AB EIA.…”

“…Similar to culture, GDH can detect the presence of C. difficile regardless of toxin production, and it is thought to replace the C. difficile culture, as it can detect C. difficile with a sensitivity of 90% or more. 10 The most commonly used culture kit is ChromeID Agar (bioMérieux, Marcy-l'Étoile, France), which was the most commonly used in the 2015 survey as well, and it is preferred since it can screen the C. difficile colony relatively well with color reaction.…”

“…The sensitivity of toxin AB EIA is low, such that the pooled sensitivity of toxin AB EIA was about 60% and may be less than that depending on the method. 5 10 The fact that perception by some specialists who actually perform the tests in Korea was positive could be due to the automated EIA method, which is the most commonly used method, and is more sensitive than other methods. 10 The perception of sensitivity and specificity of NAAT was mostly positive, suggesting that the specialists were quite satisfied, consistent with the fact that sensitivity and specificity of NAAT are known to be remarkable.…”

“… 5 10 The fact that perception by some specialists who actually perform the tests in Korea was positive could be due to the automated EIA method, which is the most commonly used method, and is more sensitive than other methods. 10 The perception of sensitivity and specificity of NAAT was mostly positive, suggesting that the specialists were quite satisfied, consistent with the fact that sensitivity and specificity of NAAT are known to be remarkable. 5 10 The relatively lower specificity of C. difficile culture encountered by some could be due to the characteristics of the culture containing non-specific bacteria with a specificity of 60–80%.…”

Comparison of commercial assays and two-step approach to detect Clostridioides difficile in South Africa

“… 23 nucleic acid amplification tests may detect asymptomatic carriage due to possible non-expression of the toxin encoding gene and therefore the clinical specificity may be lower than reported. 24 In their meta-analysis conducted in 2019, Kraft et al reported an estimated sensitivity of 94% and a specificity of 97% when NAATs were compared to either cell culture neutralisation assay or TC or both in studies where it was specifically stated that stools were only included if conforming to the shape of the container. 10 …”