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A 2-step algorithm combining glutamate dehydrogenase and nucleic acid amplification tests for the detection of Clostridioides difficile in stool specimens

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Abstract

The optimized diagnosis algorithm of Clostridioides difficile infection (CDI) is worldwide concerns. The purpose of this study was to assess the toxigenic C. difficile test performance and propose an optimal laboratory workflow for the diagnosis of CDI in mild virulent epidemic areas. Diarrhea samples collected from patients were analyzed by glutamate dehydrogenase (GDH), toxin AB (CDAB), and nucleic acid amplification test (NAAT). We assessed the performance of GDH, the GDH-CDAB algorithm, and the GDH-NAAT algorithm using toxigenic culture (TC) as a reference method. In this study, 186 diarrhea samples were collected. The numbers of TC-positive and TC-negative samples were 39 and 147, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of the GDH assay were 100%, 80.3%, 57.4%, 100%, and 0.63; of the GDH-CDAB algorithm were 48.7%, 97.3%, 82.6%, 87.7%, and 0.54; and of the GDH-NAAT algorithm were 74.4%, 100%, 100%, 93.6%, and 0.82, respectively. The GDH-NAAT algorithm has great concordance with TC in detecting toxigenic C. difficile (kappa = 0.82), while the sensitivity of the GDH-CDAB algorithm was too low to meet the demand of CDI diagnosis clinically. GDH-NAAT algorithm is recommended for the detection of toxigenic C. difficile with high specificity, increased sensitivity, and cost-effective.

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Acknowledgments

We are grateful to members of the Department of Laboratory Medicine of the First Affiliated Hospital with Nanjing Medical University for their significant suggestions and to all patients who provided biological specimens.

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Author notes

  1. Chengcheng Liu and Chenjie Tang contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, National Key Clinical Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Chengcheng Liu, Yaping Han, Yuqiao Xu, Fang Ni & Genyan Liu

  2. Department of Laboratory Medicine, Wuxi Children’s Hospital, The Affiliated Wuxi Children’s Hospital of Nanjing Medical University, Wuxi, 214000, People’s Republic of China

    Chenjie Tang

  3. Department of Infection Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Ke Jin

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  1. Chengcheng Liu
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Contributions

Concept and design: Chengcheng Liu, Chenjie Tang, and Genyan Liu

Acquisition of data: Chengcheng Liu, Chenjie Tang, and Yaping Han

Statistical analysis: Chenjie Tang and Yuqiao Xu

Interpretation of results: Fang Ni, Ke Jin, and Chengcheng Liu

Writing of the manuscript: Chengcheng Liu, Chenjie Tang, and Genyan Liu

Critical revision of the manuscript for important intellectual content: all authors

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Correspondence to Genyan Liu.

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Ethical approval was waived by the hospital ethics committee in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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The authors declare that they have no conflict of interest.

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Liu, C., Tang, C., Han, Y. et al. A 2-step algorithm combining glutamate dehydrogenase and nucleic acid amplification tests for the detection of Clostridioides difficile in stool specimens. Eur J Clin Microbiol Infect Dis 40, 345–351 (2021). https://doi.org/10.1007/s10096-020-04027-y

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