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Author Notes:

Address correspondence to Colleen S. Kraft, colleen.kraft@emory.edu, or James W. Snyder, jwsnyd01@louisville.edu.

ACKNOWLEDGMENTS: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

We thank the LMBP Work Group, L. Clifford McDonald, Dale Gerding, and Catherine Duff as a patient advocate.

Vickie Baselski, Susan Benson, Cassiana E. Bittencourt, April M. Bobenchik, Nancy E. Cornish, Jennifer Dien Bard, Peter Gilligan, Jonathan C. Gullett, Colleen S. Kraft, Joseph D. Lutgring, Thomas J. Kirn, Irving Nachamkin, J. Scott Parrott, Matthew L. Rubinstein, Robert L. Sautter, and James W. Snyder have no conflicts to declare.

Monika Fischer has received honoraria from Finch Therapeutics for consulting.

This company is involved in development of diagnostics targeted at the human microbiome, which has relevance to C. difficile diagnosis and treatment. Romney M. Humphries has received speaking and consulting honoraria from Meridian, Cepheid, and Nanosphere. He also serves as CSO of a diagnostics company.

Elizabeth M. Marlowe, over the course of this meta-analysis, became an employee of a manufacturer of a C.Diff NAAT assay, but this assay was not evaluated in this systematic review.

Nancy S. Miller has had recent research funding and a percentage of her salary from a diagnostic company performing C. difficile clinical trials.

Alice S. Weissfeld has performed clinical trials for C. difficile testing. Since 2009, her company, Microbiology Specialists Inc., has performed toxigenic C. difficile cultures for clinical trials run by Cepheid, BD, Nanosphere, and IMDx.

These companies used the data to gain 510 k clearances from the FDA.

The company has since worked with Diasorin Inc. (formerly Focus Diagnostics), Luminex Corporation, and GenePOC Inc. Sandra S. Richter has received research funding from Roche, bioMérieux, BD Diagnostics, Hologic, Accelerate, and Diasorin.

Subject:

Research Funding:

This work received funding from the American Society for Microbiology (5U47OE000055).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • C. difficile infection
  • diagnostic accuracy
  • laboratory diagnosis
  • meta-analysis
  • systematic review
  • REAL-TIME PCR
  • POLYMERASE-CHAIN-REACTION
  • GENOMERA C. DIFFICILE
  • 3 ENZYME IMMUNOASSAYS
  • 2 MOLECULAR METHODS
  • BD GENEOHM CDIFF
  • MULTICENTER EVALUATION
  • 2-STEP ALGORITHM
  • RAPID DIAGNOSIS
  • CYTOTOXICITY ASSAY

A Laboratory Medicine Best Practices Systematic Review and Meta-analysis of Nucleic Acid Amplification Tests (NAATs) and Algorithms Including NAATs for the Diagnosis of Clostridioides (Clostridium) difficile in Adults

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Journal Title:

Clinical Microbiology Reviews

Volume:

Volume 32, Number 3

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Type of Work:

Article | Final Publisher PDF

Abstract:

SUMMARY: The evidence base for the optimal laboratory diagnosis of Clostridioides (Clostridium) difficile in adults is currently unresolved due to the uncertain performance characteristics and various combinations of tests. This systematic review evaluates the diagnostic accuracy of laboratory testing algorithms that include nucleic acid amplification tests (NAATs) to detect the presence of C. difficile The systematic review and meta-analysis included eligible studies (those that had PICO [population, intervention, comparison, outcome] elements) that assessed the diagnostic accuracy of NAAT alone or following glutamate dehydrogenase (GDH) enzyme immunoassays (EIAs) or GDH EIAs plus C. difficile toxin EIAs (toxin). The diagnostic yield of NAAT for repeat testing after an initial negative result was also assessed. Two hundred thirty-eight studies met inclusion criteria. Seventy-two of these studies had sufficient data for meta-analysis. The strength of evidence ranged from high to insufficient. The uses of NAAT only, GDH-positive EIA followed by NAAT, and GDH-positive/toxin-negative EIA followed by NAAT are all recommended as American Society for Microbiology (ASM) best practices for the detection of the C. difficile toxin gene or organism. Meta-analysis of published evidence supports the use of testing algorithms that use NAAT alone or in combination with GDH or GDH plus toxin EIA to detect the presence of C. difficile in adults. There is insufficient evidence to recommend against repeat testing of the sample using NAAT after an initial negative result due to a lack of evidence of harm (i.e., financial, length of stay, or delay of treatment) as specified by the Laboratory Medicine Best Practices (LMBP) systematic review method in making such an assessment. Findings from this systematic review provide clarity to diagnostic testing strategies and highlight gaps, such as low numbers of GDH/toxin/PCR studies, in existing evidence on diagnostic performance, which can be used to guide future clinical research studies.

Copyright information:

© 2019 Kraft et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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