{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:14:11Z","timestamp":1789910051793,"version":"4.0.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Conventional culture-based drug susceptibility testing (DST) for the second-line antituberculosis drugs is slow, leading to diagnostic delay with associated exacerbation of transmission, amplification of resistance, and increased mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To assess the diagnostic performance of the GenoType MTBDRsl line probe assay (LPA) for the rapid detection of mutations conferring resistance to ofloxacin (OFX), amikacin (AMK), and ethambutol and to determine the impact of implementation on the turnaround time in a high-throughput diagnostic laboratory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Six hundred and fifty-seven direct patient acid-fast bacilli smear-positive specimens resistant to isoniazid, rifampin, or both according to the GenoType MTBDRplus assay were consecutively tested, using the GenoType MTBDRsl LPA. The diagnostic performance was assessed relative to the \u201cgold standard\u201d culture-based method, and the laboratory turnaround times for both methods were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>A total of 516 of 657 patient specimens had valid results for both tests. The sensitivity for detecting OFX, AMK, and extensive drug resistance, using the GenoType MTBDRsl LPA, was 90.7% (95% confidence interval [CI], 80.1\u201396.0%), 100% (95% CI, 91.8\u2013100%), and 92.3% (95% CI, 75.9\u201397.9%), respectively, and the specificity for detection was 98.1% (95% CI, 96.3\u201399.0%), 99.4% (95% CI, 98.2\u201399.8%), and 99.6% (95% CI, 98.5\u201399.9%), respectively. Implementation of this test significantly reduced the turnaround time by 93.3% (P &amp;lt; 0.001), calculated from the date that the specimen was received at the laboratory to reporting second-line results. In addition, a significant increase in diagnostic yield of 20.1% and 19.3% (P &amp;lt; 0.001) for OFX and AMK resistance, respectively, was obtained for isolates that were either contaminated or had lost viability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The GenoType MTBDRsl LPA is a rapid and reliable DST that can be easily incorporated into the diagnostic algorithm. This assay significantly improved diagnostic yield (P &amp;lt; 0.001) while simultaneously decreasing diagnostic delay for reporting second-line DST. The rapid dissemination of second-line DST results will guide initiation of appropriate treatment, thereby reducing transmission and improving treatment outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201205-0960oc","type":"journal-article","created":{"date-parts":[[2012,12,17]],"date-time":"2012-12-17T12:29:03Z","timestamp":1355747343000},"page":"1298-1305","source":"Crossref","is-referenced-by-count":42,"title":["GenoType MTBDR\n                    <i>sl<\/i>\n                    Line Probe Assay Shortens Time to Diagnosis of Extensively Drug-Resistant Tuberculosis in a High-Throughput Diagnostic Laboratory"],"prefix":"10.1093","volume":"186","author":[{"given":"Marinus","family":"Barnard","sequence":"first","affiliation":[{"name":"National Health Laboratory Service (NHLS), Tuberculosis Reference Laboratory, Green Point, Cape Town, South Africa"},{"name":"Department of Science and Technology\/National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, University of Stellenbosch\/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Science and Technology\/National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, University of Stellenbosch\/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico Gey","family":"Van Pittius","sequence":"additional","affiliation":[{"name":"Department of Science and Technology\/National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, University of Stellenbosch\/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"van Helden","sequence":"additional","affiliation":[{"name":"Department of Science and Technology\/National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, University of Stellenbosch\/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlein","family":"Bosman","sequence":"additional","affiliation":[{"name":"National Health Laboratory Service (NHLS), Tuberculosis Reference Laboratory, Green Point, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Streicher","sequence":"additional","affiliation":[{"name":"Department of Science and Technology\/National Research Foundation Centre of Excellence in Biomedical Tuberculosis Research, University of Stellenbosch\/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Coetzee","sequence":"additional","affiliation":[{"name":"National TB Reference Laboratory, NHLS, Sandringham, Johannesburg, South Africa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Foundation for Innovative New Diagnostics, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,15]]},"reference":[{"key":"2026032101040485900_bib1","author":"World Health Organization","year":"2011"},{"key":"2026032101040485900_bib2","author":"World Health Organization","year":"2008"},{"key":"2026032101040485900_bib3","author":"World Health Organization"},{"key":"2026032101040485900_bib4","first-page":"301","article-title":"Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs worldwide, 2000\u20132004","volume":"55","author":"Centers for Disease Control and Prevention","year":"2006","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2026032101040485900_bib5","author":"World Health Organization","year":"2010"},{"key":"2026032101040485900_bib6","author":"Stop TB Department, World Health Organization"},{"key":"2026032101040485900_bib7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1586\/ers.09.45","article-title":"Drug-susceptibility testing in TB: current status and future prospects","volume":"3","author":"Richter","year":"2009","journal-title":"Expert Rev Respir Med"},{"key":"2026032101040485900_bib8","first-page":"1157","article-title":"Is second-line anti-tuberculosis drug susceptibility testing reliable?","volume":"8","author":"Kim","year":"2004","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib9","first-page":"99","article-title":"Genotypic diversity of extensively drug\u2013resistant tuberculosis (XDR-TB) in South Africa","volume":"12","author":"Mlambo","year":"2008","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/JCM.40.2.607-610.2002","article-title":"Evaluation of automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to four major antituberculous drugs: comparison with the radiometric BACTEC 460TB method and the agar plate method of proportion","volume":"40","author":"Tortoli","year":"2002","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib11","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1016\/S0140-6736(06)69573-1","article-title":"Extensively drug\u2013resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa","volume":"368","author":"Gandhi","year":"2006","journal-title":"Lancet"},{"key":"2026032101040485900_bib12","article-title":"Molecular line probe assays for rapid screening of patients at risk of multi-drug resistant tuberculosis (MDR-TB)","author":"World Health Organization","year":"2008"},{"key":"2026032101040485900_bib13","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1128\/JCM.00081-09","article-title":"Feasibility of the GenoType MTBDRsl assay for fluoroquinolone, amikacin\u2013capreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens","volume":"47","author":"Hillemann","year":"2009","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib14","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1128\/JCM.00201-10","article-title":"Evaluation of the MTBDRsl test for detection of second-line-drug resistance in Mycobacterium tuberculosis","volume":"48","author":"Kiet","year":"2010","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.5588\/ijtld.10.0600","article-title":"Evaluation of the GenoType\u00ae MTBDRsl assay for susceptibility testing of second-line anti-tuberculosis drugs","volume":"16","author":"Said","year":"2012","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib16","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1128\/JCM.00039-12","article-title":"Detection of resistance to second-line antituberculosis drugs using the GenoType\u00ae MTBDRsl assay: a multi-center evaluation and feasibility study","volume":"50","author":"Ignatyeva","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1183\/09031936.00164111","article-title":"GenoType MTBDRsl performance on clinical samples with diverse genetic background","volume":"40","author":"Miotto","year":"2012","journal-title":"Eur Respir J"},{"key":"2026032101040485900_bib18","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1128\/JCM.05274-11","article-title":"GenoType MTBDRsl for molecular detection of second-line-drug and ethambutol resistance in Mycobacterium tuberculosis strains and clinical samples","volume":"50","author":"Lacoma","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib19","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1128\/JCM.00197-11","article-title":"Performance assessment of the GenoType MTBDRsl test and DNA sequencing for detection of second-line and ethambutol drug resistance among patients infected with multidrug-resistant Mycobacterium tuberculosis","volume":"49","author":"Huang","year":"2011","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib20","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1128\/JCM.01947-09","article-title":"Detection by GenoType MTBDRsl test of complex mechanisms of resistance to second-line drugs and ethambutol in multidrug-resistant Mycobacterium tuberculosis complex isolates","volume":"48","author":"Brossier","year":"2010","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib21","author":"Kent"},{"key":"2026032101040485900_bib22","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1164\/rccm.200709-1436OC","article-title":"Rapid molecular screening for multidrug-resistant tuberculosis in a high-volume public health laboratory in South Africa","volume":"177","author":"Barnard","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101040485900_bib23","author":"International Organization for Standardization"},{"key":"2026032101040485900_bib24","author":"Heifets"},{"key":"2026032101040485900_bib25","first-page":"68","article-title":"Ethambutol resistance testing by mutation detection","volume":"10","author":"Johnson","year":"2006","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib26","article-title":"MGIT procedure manual prepared for the FIND MGIT demonstration project","author":"Siddiqi","year":"2005"},{"key":"2026032101040485900_bib27","author":"Centers for Disease Control and Prevention"},{"key":"2026032101040485900_bib28","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1128\/AAC.05905-11","article-title":"Mycobacterium tuberculosis population structure determines the outcome of genetics-based second-line drug resistance testing","volume":"56","author":"Streicher","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101040485900_bib29","first-page":"748","article-title":"Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO\/IUATLD Supranational Reference Laboratory Network: five rounds of proficiency testing, 1994\u20131998","volume":"6","author":"Laszlo","year":"2002","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib30","doi-asserted-by":"crossref","first-page":"8076","DOI":"10.2807\/ese.13.12.08076-en","article-title":"The added value of a European Union tuberculosis reference laboratory network\u2014analysis of the national reference laboratory activities","volume":"13","author":"Drobniewski","year":"2008","journal-title":"Euro Surveill"},{"key":"2026032101040485900_bib31","doi-asserted-by":"crossref","first-page":"3192","DOI":"10.1128\/AAC.49.8.3192-3197.2005","article-title":"Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis","volume":"49","author":"Maus","year":"2005","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101040485900_bib32","doi-asserted-by":"crossref","first-page":"e33275","DOI":"10.1371\/journal.pone.0033275","article-title":"Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review","volume":"7","author":"Georghiou","year":"2012","journal-title":"PLoS One"},{"key":"2026032101040485900_bib33","first-page":"S301","article-title":"Assesment of the GenoType\u00ae MTBDRsl line probe assay for the rapid diagnosis of XDR-TB in South Africa [abstract]","volume":"14","author":"Barnard","year":"2010","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib34","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1128\/AAC.01550-10","article-title":"Molecular detection of mutations associated with first- and second-line drug resistance compared with conventional drug susceptibility testing of Mycobacterium tuberculosis","volume":"55","author":"Campbell","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101040485900_bib35","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1128\/AAC.00036-08","article-title":"Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from Russia","volume":"52","author":"Mokrousov","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101040485900_bib36","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.1128\/JCM.01209-09","article-title":"Mycobacterium tuberculosis strains with highly discordant rifampin susceptibility test results","volume":"47","author":"Van Deun","year":"2009","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib37","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1128\/JCM.05793-11","article-title":"Subpopulation analysis of heteroresistance to fluoroquinolone in Mycobacterium tuberculosis isolates from Beijing, China","volume":"50","author":"Zhang","year":"2012","journal-title":"J Clin Microbiol"},{"key":"2026032101040485900_bib38","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1164\/rccm.200907-0989OC","article-title":"HIV coinfection in multidrug- and extensively drug\u2013resistant tuberculosis results in high early mortality","volume":"181","author":"Gandhi","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101040485900_bib39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.5588\/ijtld.11.0153","article-title":"Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting","volume":"16","author":"Gandhi","year":"2012","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib40","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/BF03256410","article-title":"Detecting drug-resistant tuberculosis: the importance of rapid testing","volume":"15","author":"Hoek","year":"2011","journal-title":"Mol Diagn Ther"},{"key":"2026032101040485900_bib41","doi-asserted-by":"crossref","first-page":"196","DOI":"10.5588\/ijtld.11.0116","article-title":"Rise in rifampicin-monoresistant tuberculosis in Western Cape, South Africa","volume":"16","author":"Mukinda","year":"2012","journal-title":"Int J Tuberc Lung Dis"},{"key":"2026032101040485900_bib42","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1128\/CMR.00059-10","article-title":"Laboratory diagnosis of tuberculosis in resource-poor countries: challenges and opportunities","volume":"24","author":"Parsons","year":"2011","journal-title":"Clin Microbiol Rev"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/186\/12\/1298\/67248074\/ajrccm_186_12_1298.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/186\/12\/1298\/67248074\/ajrccm_186_12_1298.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:04:13Z","timestamp":1774069453000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/186\/12\/1298\/8507818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2012,12,15]]},"published-print":{"date-parts":[[2012,12,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201205-0960oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,12]]},"published":{"date-parts":[[2012,12]]}}}