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Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility
Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtite...
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Published in: | Journal of clinical microbiology 2019-04, Vol.57 (4) |
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description | Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories. The SensiTitre Vizion digital MIC viewing system (Vizion) offers a more streamlined approach using semiautomated reading. Here, we conducted a blinded trial comparing the outcome of AST between manual readout and Vizion readout for 132 NTM isolates, amounting to 727 individual tests for antibiotic susceptibility ranging across 13 individual antibiotics with established CLSI breakpoints. From this, we calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the F1 value, as well as assessing major error (ME) and very major error (VME) rates. We find that Vizion-assisted AST produces significantly lower MICs (paired Wilcox signed rank test;
< 0.0001). The Vizion had an accuracy of 89,40%, producing 61 MEs (8.39%) and 16 VMEs (2.20%). The calculated specificity was 0.8370, the sensitivity was 0.9550, the PPV was 0.8460, the NPV was 0.9520, and the F1 score was 0.8970. We show that discrepant readings mostly stem from CLSI guideline breakpoints being close to, or overlapping, the MIC
values, leading to small discrepancies crossing the breakpoint, contributing to VMEs and MEs. Using the Vizion in standard clinical diagnostics for NTM might lead to an overestimation of antibiotic susceptibility. |
doi_str_mv | 10.1128/JCM.01756-18 |
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< 0.0001). The Vizion had an accuracy of 89,40%, producing 61 MEs (8.39%) and 16 VMEs (2.20%). The calculated specificity was 0.8370, the sensitivity was 0.9550, the PPV was 0.8460, the NPV was 0.9520, and the F1 score was 0.8970. We show that discrepant readings mostly stem from CLSI guideline breakpoints being close to, or overlapping, the MIC
values, leading to small discrepancies crossing the breakpoint, contributing to VMEs and MEs. Using the Vizion in standard clinical diagnostics for NTM might lead to an overestimation of antibiotic susceptibility.</description><identifier>ISSN: 0095-1137</identifier><identifier>EISSN: 1098-660X</identifier><identifier>DOI: 10.1128/JCM.01756-18</identifier><identifier>PMID: 30760530</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Anti-Bacterial Agents - pharmacology ; Humans ; Microbial Sensitivity Tests - instrumentation ; Microbial Sensitivity Tests - standards ; Mycobacteriology and Aerobic Actinomycetes ; Mycobacterium Infections, Nontuberculous - diagnosis ; Mycobacterium Infections, Nontuberculous - microbiology ; Nontuberculous Mycobacteria - drug effects ; Nontuberculous Mycobacteria - isolation & purification ; Sensitivity and Specificity</subject><ispartof>Journal of clinical microbiology, 2019-04, Vol.57 (4)</ispartof><rights>Copyright © 2019 American Society for Microbiology.</rights><rights>Copyright © 2019 American Society for Microbiology. 2019 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-9d6b4c34777cda39c756cc0c58633a2d0388ad6a166ec354f4b794cf8b0d43d63</citedby><cites>FETCH-LOGICAL-c384t-9d6b4c34777cda39c756cc0c58633a2d0388ad6a166ec354f4b794cf8b0d43d63</cites><orcidid>0000-0002-0581-2003 ; 0000-0003-3343-6823 ; 0000-0003-0281-4895</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440788/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440788/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3188,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30760530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Land, Geoffrey A.</contributor><creatorcontrib>Rockland, Mariëlle</creatorcontrib><creatorcontrib>Ruth, Mike Marvin</creatorcontrib><creatorcontrib>Aalders, Nicole</creatorcontrib><creatorcontrib>Pennings, Lian</creatorcontrib><creatorcontrib>Hoefsloot, Wouter</creatorcontrib><creatorcontrib>Wattenberg, Melanie</creatorcontrib><creatorcontrib>van Ingen, Jakko</creatorcontrib><title>Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility</title><title>Journal of clinical microbiology</title><addtitle>J Clin Microbiol</addtitle><description>Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories. The SensiTitre Vizion digital MIC viewing system (Vizion) offers a more streamlined approach using semiautomated reading. Here, we conducted a blinded trial comparing the outcome of AST between manual readout and Vizion readout for 132 NTM isolates, amounting to 727 individual tests for antibiotic susceptibility ranging across 13 individual antibiotics with established CLSI breakpoints. From this, we calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the F1 value, as well as assessing major error (ME) and very major error (VME) rates. We find that Vizion-assisted AST produces significantly lower MICs (paired Wilcox signed rank test;
< 0.0001). The Vizion had an accuracy of 89,40%, producing 61 MEs (8.39%) and 16 VMEs (2.20%). The calculated specificity was 0.8370, the sensitivity was 0.9550, the PPV was 0.8460, the NPV was 0.9520, and the F1 score was 0.8970. We show that discrepant readings mostly stem from CLSI guideline breakpoints being close to, or overlapping, the MIC
values, leading to small discrepancies crossing the breakpoint, contributing to VMEs and MEs. Using the Vizion in standard clinical diagnostics for NTM might lead to an overestimation of antibiotic susceptibility.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Humans</subject><subject>Microbial Sensitivity Tests - instrumentation</subject><subject>Microbial Sensitivity Tests - standards</subject><subject>Mycobacteriology and Aerobic Actinomycetes</subject><subject>Mycobacterium Infections, Nontuberculous - diagnosis</subject><subject>Mycobacterium Infections, Nontuberculous - microbiology</subject><subject>Nontuberculous Mycobacteria - drug effects</subject><subject>Nontuberculous Mycobacteria - isolation & purification</subject><subject>Sensitivity and Specificity</subject><issn>0095-1137</issn><issn>1098-660X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdkUFv1DAQhS0Eokvhxhn5yIGU8dqxnQtStSp0UZceChI3a2I7YJTEwXGK9n_wg_HSpQJOPvibN_PeI-Q5gzPG1vr1-83uDJiqZcX0A7Ji0OhKSvj8kKwAmrpijKsT8mSevwEwIer6MTnhoCTUHFbk53aYej_4MWMOcaSxozd-CLjkOGD2jp6POQzBptgG7OnNMls_5dCGPuQ93Y7Zpyn54_AlJvcDk6ddTPRDHPPS-mSXPi4z3e1tbNEWPiDd4Z5e3_rk5yJe1vyn-5Q86rCf_bPje0o-vb34uLmsrq7fbTfnV5XlWuSqcbIVlgullHXIG1tCsBZsrSXnuHbAtUYnkUnpLa9FJ1rVCNvpFpzgTvJT8uZOd1rawTtbUkjYmymVo9LeRAzm358xfDVf4q2RQoDSugi8PAqk-H0pbswQipG-x9EX02a9BlCKc3VAX92hJcp5Tr67X8PAHIo0pUjzu0jDDviLv0-7h_80x38BO7mfWQ</recordid><startdate>20190401</startdate><enddate>20190401</enddate><creator>Rockland, Mariëlle</creator><creator>Ruth, Mike Marvin</creator><creator>Aalders, Nicole</creator><creator>Pennings, Lian</creator><creator>Hoefsloot, Wouter</creator><creator>Wattenberg, Melanie</creator><creator>van Ingen, Jakko</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0581-2003</orcidid><orcidid>https://orcid.org/0000-0003-3343-6823</orcidid><orcidid>https://orcid.org/0000-0003-0281-4895</orcidid></search><sort><creationdate>20190401</creationdate><title>Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility</title><author>Rockland, Mariëlle ; Ruth, Mike Marvin ; Aalders, Nicole ; Pennings, Lian ; Hoefsloot, Wouter ; Wattenberg, Melanie ; van Ingen, Jakko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-9d6b4c34777cda39c756cc0c58633a2d0388ad6a166ec354f4b794cf8b0d43d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Humans</topic><topic>Microbial Sensitivity Tests - instrumentation</topic><topic>Microbial Sensitivity Tests - standards</topic><topic>Mycobacteriology and Aerobic Actinomycetes</topic><topic>Mycobacterium Infections, Nontuberculous - diagnosis</topic><topic>Mycobacterium Infections, Nontuberculous - microbiology</topic><topic>Nontuberculous Mycobacteria - drug effects</topic><topic>Nontuberculous Mycobacteria - isolation & purification</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rockland, Mariëlle</creatorcontrib><creatorcontrib>Ruth, Mike Marvin</creatorcontrib><creatorcontrib>Aalders, Nicole</creatorcontrib><creatorcontrib>Pennings, Lian</creatorcontrib><creatorcontrib>Hoefsloot, Wouter</creatorcontrib><creatorcontrib>Wattenberg, Melanie</creatorcontrib><creatorcontrib>van Ingen, Jakko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical microbiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rockland, Mariëlle</au><au>Ruth, Mike Marvin</au><au>Aalders, Nicole</au><au>Pennings, Lian</au><au>Hoefsloot, Wouter</au><au>Wattenberg, Melanie</au><au>van Ingen, Jakko</au><au>Land, Geoffrey A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility</atitle><jtitle>Journal of clinical microbiology</jtitle><addtitle>J Clin Microbiol</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>57</volume><issue>4</issue><issn>0095-1137</issn><eissn>1098-660X</eissn><abstract>Nontuberculous mycobacteria (NTM) cause severe opportunistic infections and have a rising incidence in most settings. Rising diagnostic need must be met by national reference laboratories, which rely on Clinical and Laboratory Standards Institute (CLSI) guideline-approved manual readout of microtiter plates for antimicrobial susceptibility testing (AST) to determine antibiotic minimum inhibitory concentrations (MICs). Interpretation of these plates leads to different outcomes between laboratories. The SensiTitre Vizion digital MIC viewing system (Vizion) offers a more streamlined approach using semiautomated reading. Here, we conducted a blinded trial comparing the outcome of AST between manual readout and Vizion readout for 132 NTM isolates, amounting to 727 individual tests for antibiotic susceptibility ranging across 13 individual antibiotics with established CLSI breakpoints. From this, we calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and the F1 value, as well as assessing major error (ME) and very major error (VME) rates. We find that Vizion-assisted AST produces significantly lower MICs (paired Wilcox signed rank test;
< 0.0001). The Vizion had an accuracy of 89,40%, producing 61 MEs (8.39%) and 16 VMEs (2.20%). The calculated specificity was 0.8370, the sensitivity was 0.9550, the PPV was 0.8460, the NPV was 0.9520, and the F1 score was 0.8970. We show that discrepant readings mostly stem from CLSI guideline breakpoints being close to, or overlapping, the MIC
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subjects | Anti-Bacterial Agents - pharmacology Humans Microbial Sensitivity Tests - instrumentation Microbial Sensitivity Tests - standards Mycobacteriology and Aerobic Actinomycetes Mycobacterium Infections, Nontuberculous - diagnosis Mycobacterium Infections, Nontuberculous - microbiology Nontuberculous Mycobacteria - drug effects Nontuberculous Mycobacteria - isolation & purification Sensitivity and Specificity |
title | Implementation of Semiautomated Antimicrobial Susceptibility Interpretation Hardware for Nontuberculous Mycobacteria May Overestimate Susceptibility |
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