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Updated: Jun 25, 2026

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
Published on: December 10, 2016
Laboratory Diagnostic Methods for Clostridioides difficile Infection: the First Systematic Review and Meta-analysis
Hae-Sun Chung1, Jeong Su Park2, Bo-Moon Shin3
1Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul, Korea.
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.
Insights
Glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) and nucleic acid amplification tests (NAATs) offer high sensitivity for diagnosing Clostridioides difficile infection (CDI). Toxin A and B EIAs are less sensitive but highly specific.
Area of Science:
- Clinical Microbiology
- Infectious Diseases
- Diagnostic Accuracy Studies
Background:
- Clostridioides difficile infection (CDI) diagnosis relies on various laboratory methods.
- Accurate and timely diagnosis is crucial for effective patient management and infection control.
Purpose of the Study:
- To systematically analyze and compare the performance of current laboratory diagnostic methods for CDI.
- To provide data to inform the selection of optimal diagnostic strategies for CDI.
Main Methods:
- Systematic review and meta-analysis of studies from major databases (PubMed, Web of Science, Cochrane Library, KoreaMed).
- Evaluation of glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs), toxin A and B EIAs, and nucleic acid amplification tests (NAATs).
- Calculation of pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) against toxigenic culture.
Main Results:
- Pooled sensitivities/specificities: GDH EIAs (92.7%/94.6%), Toxin AB EIAs (57.9%/97.0%), NAATs (90.0%/95.8%).
- Automated EIAs and specific NAATs (Xpert C. difficile) demonstrated superior sensitivity.
- Predictive values varied with CDI prevalence; high NPVs at low prevalence, high PPVs at high prevalence.
Conclusions:
- GDH EIAs and NAATs exhibit high sensitivity for CDI diagnosis.
- Toxin AB EIAs, while less sensitive, offer the highest specificity.
- Findings offer valuable insights for optimizing CDI laboratory diagnostics.
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