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

• Type of Material: Article
• Authors: Colleen Kraft, Emory University; J. Scott Parrott, Rutgers University; Nancy E. Cornish, Centers for Disease Control and Prevention; Matthew L. Rubinstein, Centers for Disease Control and Prevention; Alice S. Weissfeld, Microbiol Specialists Inc; Peggy McNult, American Society for Microbiology; Irving Nachamkin, University of Pennsylvania; Romney M. Humphries, Accelerate Diagnostics; Thomas J. Kirn, Rutgers University; Jennifer Dien Bard, Children’s Hospital Los Angeles; Joseph Daniel Lutgring, Emory University; Jonathan C. Gullett, Kaiser Permanente; Cassiana E. Bittencourt, University of California Irvine; Susan Benson, PathWest Laboratory Medicine; April M. Bobenchik, University of Western Australia; Robert L. Sautter, RL Sautter Consulting LLC; Vickie Baselski, University of Tennessee; Michel C. Atlas, University of Louisville; Elizabeth M. Marlowe, Roche Molecular Systems; Nancy S. Miller, Boston Medical Center; Monika Fischer, Indiana University; Sandra S. Richter, Cleveland Clinic; Peter Gilligan, University of North Carolina; James W. Snyder, University of Louisville
• Language: English
• Date: 2019-07-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Kraft et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1128/CMR.00032-18
• Title of Journal or Parent Work: Clinical Microbiology Reviews
• ISSN: 0893-8512
• Volume: 32
• Issue: 3
• Grant/Funding Information: This work received funding from the American Society for Microbiology (5U47OE000055).
• Keywords: laboratory diagnosis; 2-STEP ALGORITHM; 2 MOLECULAR METHODS; diagnostic accuracy; Microbiology; CYTOTOXICITY ASSAY; 3 ENZYME IMMUNOASSAYS; systematic review; BD GENEOHM CDIFF; MULTICENTER EVALUATION; GENOMERA C. DIFFICILE; RAPID DIAGNOSIS; meta-analysis; REAL-TIME PCR; C. difficile infection; Science & Technology; POLYMERASE-CHAIN-REACTION; Life Sciences & Biomedicine
• Research Categories: Biology, Microbiology

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.