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Clin Microbiol Rev. 2019 May 29;32(3). pii: e00032-18. doi: 10.1128/CMR.00032-18. Print 2019 Jun 19.

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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Emory University School of Medicine, Atlanta, Georgia, USA
Department of Interdisciplinary Studies, School of Health Professions, Rutgers University, Newark, New Jersey, USA.
Department of Epidemiology, School of Public Health, Rutgers University, Piscataway, New Jersey, USA.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Microbiology Specialists Incorporated, Houston, Texas, USA.
American Society for Microbiology, Washington, DC, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Accelerate Diagnostics, Tucson, Arizona, USA.
Children's Hospital Los Angeles, Los Angeles, California, USA.
Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Emory University School of Medicine, Atlanta, Georgia, USA.
Kaiser Permanente (Southern California Permanente Medical Group) Regional Reference Laboratories, Greater Los Angeles, Los Angeles, California, USA.
University of California-Irvine, Orange, California, USA.
PathWest Laboratory Medicine, Perth, Western Australia, Australia.
University of Western Australia, Perth, Western Australia, Australia.
Rhode Island Hospital/Lifespan Academic Medical Center, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
RL Sautter Consulting LLC, Lancaster, South Carolina, USA.
University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Kornhauser Health Sciences Library, University of Louisville, Louisville, Kentucky, USA.
Roche Molecular Systems, Pleasanton, California, USA.
Boston Medical Center, Boston, Massachusetts, USA.
Boston University School of Medicine, Boston, Massachusetts, USA.
Indiana University, Indianapolis, Indiana, USA.
Cleveland Clinic, Cleveland, Ohio, USA.
University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Kornhauser Health Sciences Library, University of Louisville, Louisville, Kentucky, USA


SUMMARYThe 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.


C. difficile infection; diagnostic accuracy; laboratory diagnosis; meta-analysis; systematic review

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