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

Colleen S. Kraft, J. Scott Parrott, Nancy E. Cornish, Matthew L. Rubinstein, Alice S. Weissfeld, Peggy McNult, Irving Nachamkin, Romney M. Humphries, Thomas J. Kirn, Jennifer Dien Bard, Joseph D. Lutgring, Jonathan C. Gullett, Cassiana E. Bittencourt, Susan Benson, April M. Bobenchik, Robert L. Sautter, Vickie Baselski, Michel C. Atlas, Elizabeth M. Marlowe, Nancy S. Miller & 4 others Monika Fischer, Sandra S. Richter, Peter Gilligan, James W. Snyder

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalClinical Microbiology Reviews
Volume32
Issue number3
DOIs
Publication statusPublished - 19 Jun 2019

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Nucleic Acid Amplification Techniques
Clostridium difficile
Glutamate Dehydrogenase
Practice Guidelines
Meta-Analysis
Immunoenzyme Techniques
Medicine
Clinical Laboratory Techniques
Microbiology
Length of Stay
Polymerase Chain Reaction

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Kraft, Colleen S. ; Parrott, J. Scott ; Cornish, Nancy E. ; Rubinstein, Matthew L. ; Weissfeld, Alice S. ; McNult, Peggy ; Nachamkin, Irving ; Humphries, Romney M. ; Kirn, Thomas J. ; Dien Bard, Jennifer ; Lutgring, Joseph D. ; Gullett, Jonathan C. ; Bittencourt, Cassiana E. ; Benson, Susan ; Bobenchik, April M. ; Sautter, Robert L. ; Baselski, Vickie ; Atlas, Michel C. ; Marlowe, Elizabeth M. ; Miller, Nancy S. ; Fischer, Monika ; Richter, Sandra S. ; Gilligan, Peter ; Snyder, James W. / 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. In: Clinical Microbiology Reviews. 2019 ; Vol. 32, No. 3.
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abstract = "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.",
keywords = "C. difficile infection, diagnostic accuracy, laboratory diagnosis, meta-analysis, systematic review",
author = "Kraft, {Colleen S.} and Parrott, {J. Scott} and Cornish, {Nancy E.} and Rubinstein, {Matthew L.} and Weissfeld, {Alice S.} and Peggy McNult and Irving Nachamkin and Humphries, {Romney M.} and Kirn, {Thomas J.} and {Dien Bard}, Jennifer and Lutgring, {Joseph D.} and Gullett, {Jonathan C.} and Bittencourt, {Cassiana E.} and Susan Benson and Bobenchik, {April M.} and Sautter, {Robert L.} and Vickie Baselski and Atlas, {Michel C.} and Marlowe, {Elizabeth M.} and Miller, {Nancy S.} and Monika Fischer and Richter, {Sandra S.} and Peter Gilligan and Snyder, {James W.}",
year = "2019",
month = "6",
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language = "English",
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journal = "Clinical Microbiology Reviews",
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Kraft, CS, Parrott, JS, Cornish, NE, Rubinstein, ML, Weissfeld, AS, McNult, P, Nachamkin, I, Humphries, RM, Kirn, TJ, Dien Bard, J, Lutgring, JD, Gullett, JC, Bittencourt, CE, Benson, S, Bobenchik, AM, Sautter, RL, Baselski, V, Atlas, MC, Marlowe, EM, Miller, NS, Fischer, M, Richter, SS, Gilligan, P & Snyder, JW 2019, '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' Clinical Microbiology Reviews, vol. 32, no. 3. https://doi.org/10.1128/CMR.00032-18

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. / Kraft, Colleen S.; Parrott, J. Scott; Cornish, Nancy E.; Rubinstein, Matthew L.; Weissfeld, Alice S.; McNult, Peggy; Nachamkin, Irving; Humphries, Romney M.; Kirn, Thomas J.; Dien Bard, Jennifer; Lutgring, Joseph D.; Gullett, Jonathan C.; Bittencourt, Cassiana E.; Benson, Susan; Bobenchik, April M.; Sautter, Robert L.; Baselski, Vickie; Atlas, Michel C.; Marlowe, Elizabeth M.; Miller, Nancy S.; Fischer, Monika; Richter, Sandra S.; Gilligan, Peter; Snyder, James W.

In: Clinical Microbiology Reviews, Vol. 32, No. 3, 19.06.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Kraft, Colleen S.

AU - Parrott, J. Scott

AU - Cornish, Nancy E.

AU - Rubinstein, Matthew L.

AU - Weissfeld, Alice S.

AU - McNult, Peggy

AU - Nachamkin, Irving

AU - Humphries, Romney M.

AU - Kirn, Thomas J.

AU - Dien Bard, Jennifer

AU - Lutgring, Joseph D.

AU - Gullett, Jonathan C.

AU - Bittencourt, Cassiana E.

AU - Benson, Susan

AU - Bobenchik, April M.

AU - Sautter, Robert L.

AU - Baselski, Vickie

AU - Atlas, Michel C.

AU - Marlowe, Elizabeth M.

AU - Miller, Nancy S.

AU - Fischer, Monika

AU - Richter, Sandra S.

AU - Gilligan, Peter

AU - Snyder, James W.

PY - 2019/6/19

Y1 - 2019/6/19

N2 - 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.

AB - 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.

KW - C. difficile infection

KW - diagnostic accuracy

KW - laboratory diagnosis

KW - meta-analysis

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