{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:13:29Z","timestamp":1790453609838,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T00:00:00Z","timestamp":1733961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research"},{"name":"EDCTP2 programme","award":["RIA2018D-2509"],"award-info":[{"award-number":["RIA2018D-2509"]}]},{"name":"EDCTP2 programme","award":["RIA2018D-2493"],"award-info":[{"award-number":["RIA2018D-2493"]}]},{"name":"EDCTP2 programme","award":["RIA2020I-3305"],"award-info":[{"award-number":["RIA2020I-3305"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["D43TW010350"],"award-info":[{"award-number":["D43TW010350"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI152087"],"award-info":[{"award-number":["U01AI152087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54EB027049"],"award-info":[{"award-number":["U54EB027049"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI136894"],"award-info":[{"award-number":["R01AI136894"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Drug susceptibility testing (DST) is essential for starting people on effective tuberculosis (TB) regimens. No published data exist for the high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects Mycobacterium tuberculosis complex (MTBC) and fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility (the latter 2 have no rapid DSTs available).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enrolled people (N = 720) with presumptive TB who provided 2 sputum samples for an Xpert MTB\/RIF Ultra assay and a culture (MTBC reference standard). Phenotypic DST and Sanger sequencing were the composite reference standards. LA-XDR on the manual FluoroLyse and automated GenoXtract fleXT (fleXT) DNA extraction methods were compared.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For MTBC, LA-XDR had similar sensitivities (85%\u201387%) and specificities (99%) using each extraction method. Drug susceptibility sensitivities (95% confidence interval) varied: 94% (86%\u201398%) for fluoroquinolones, 64% (45%\u201380%) for amikacin, and 88% (79%\u201393%) for ethambutol (specificities of 97%\u2013100%). Six of 7 (86%) resistant linezolid isolates were detected. LA-XDR with fleXT had indeterminate proportions of 21\/251 (8%), 2\/251 (1%), 63\/251 (25%), and 93\/251 (37%) for fluoroquinolones, ethambutol, amikacin, and linezolid, respectively (amikacin and linezolid indeterminates were higher with FluoroLyse-extracted DNA). In a hypothetical population of 100 smear-negative people with fluoroquinolone-resistant TB undergoing fleXT DNA extraction, 25 (25%) would be missed (1 extraction error, 2 invalid results, 15 MTBC-negative, 6 fluoroquinolone-indeterminate, and 1 false-susceptible).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>LA-XDR met the minimum World Health Organization target product profile for a next-generation, sputum-based, moderate-complexity DST with high fluoroquinolone and ethambutol resistance sensitivity, moderate amikacin resistance sensitivity, and promise for linezolid resistance, for which more data are needed. Improved LA-XDR MTBC detection would reduce missed resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciae614","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T03:04:01Z","timestamp":1733972641000},"page":"159-166","source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic Accuracy of LiquidArray MTB-XDR VER 1.0 for the Detection of <i>Mycobacterium tuberculosis<\/i> Complex, Fluoroquinolone, Amikacin, Ethambutol, and Linezolid Susceptibility"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-4944","authenticated-orcid":false,"given":"Erick","family":"Auma","sequence":"first","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2251-5534","authenticated-orcid":false,"given":"Rencia","family":"Alberts","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-2154","authenticated-orcid":false,"given":"Brigitta","family":"Derendinger","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8710-8166","authenticated-orcid":false,"given":"Rouxjeane","family":"Venter","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-1981","authenticated-orcid":false,"given":"Elizabeth M","family":"Streicher","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-4364","authenticated-orcid":false,"given":"Samantha","family":"Pillay","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2002-5240","authenticated-orcid":false,"given":"Yonas T","family":"Ghebrekristos","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]},{"name":"National Health Laboratory Service, Greenpoint Tuberculosis Laboratory , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7281-583X","authenticated-orcid":false,"given":"Moses","family":"Mburu","sequence":"additional","affiliation":[{"name":"Tuberculosis Programme, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-441X","authenticated-orcid":false,"given":"Morten","family":"Ruhwald","sequence":"additional","affiliation":[{"name":"Tuberculosis Programme, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-7358","authenticated-orcid":false,"given":"Robin","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1883-0059","authenticated-orcid":false,"given":"Adam","family":"Penn-Nicholson","sequence":"additional","affiliation":[{"name":"Tuberculosis Programme, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-2415","authenticated-orcid":false,"given":"Grant","family":"Theron","sequence":"additional","affiliation":[{"name":"Department of Science, Technology and Innovation - National Research Foundation, Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, Western Cape ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-2986","authenticated-orcid":false,"given":"Margaretha","family":"de Vos","sequence":"additional","affiliation":[{"name":"Tuberculosis Programme, FIND , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"key":"2025080104321609200_ciae614-B1","volume-title":"Global tuberculosis report 2023","author":"World Health Organization","year":"2023"},{"key":"2025080104321609200_ciae614-B2","volume-title":"WHO operational handbook on tuberculosis. Module 4: treatment: drug-resistant tuberculosis treatment, 2022 update","author":"World Health Organization","year":"2022"},{"key":"2025080104321609200_ciae614-B3","volume-title":"WHO operational handbook on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection, 3rd ed","author":"World Health Organization","year":"2024"},{"key":"2025080104321609200_ciae614-B4","doi-asserted-by":"crossref","first-page":"2178243","DOI":"10.1080\/22221751.2023.2178243","article-title":"Designing molecular diagnostics for current tuberculosis drug regimens","volume":"12","author":"Georghiou","year":"2023","journal-title":"Emerg Microbes Infect"},{"key":"2025080104321609200_ciae614-B5","first-page":"CD010705","article-title":"The diagnostic accuracy of the GenoType MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs","volume":"10","author":"Theron","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"2025080104321609200_ciae614-B6","first-page":"CD010705","article-title":"GenoType MTBDRsl assay for resistance to second-line anti-tuberculosis drugs","volume":"9","author":"Theron","year":"2016","journal-title":"Cochrane Database Syst 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accuracy and utility of FluoroType MTBDR, a new molecular assay for multidrug-resistant tuberculosis","volume":"56","author":"Vos","year":"2018","journal-title":"J Clin Microbiol"},{"key":"2025080104321609200_ciae614-B10","doi-asserted-by":"crossref","first-page":"1351.e1","DOI":"10.1016\/j.cmi.2021.04.022","article-title":"Diagnostic accuracy of the FluoroType MTB and MTBDR VER 2.0 assays for the centralized high-throughput detection of Mycobacterium tuberculosis complex DNA and isoniazid and rifampicin resistance","volume":"27","author":"Dippenaar","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"2025080104321609200_ciae614-B11","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1093\/infdis\/jiz097","article-title":"Guidance for the evaluation of tuberculosis diagnostics that meet the World Health Organization (WHO) target product profiles: an Introduction to WHO process and study design 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resistance genes of Mycobacterium tuberculosis by a dot-blot hybridization strategy","volume":"79","author":"Victor","year":"1999","journal-title":"Tuber Lung Dis"},{"key":"2025080104321609200_ciae614-B20","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/jac\/dkx094","article-title":"Examination of bedaquiline- and linezolid-resistant Mycobacterium tuberculosis isolates from the Moscow region","volume":"72","author":"Zimenkov","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2025080104321609200_ciae614-B21","volume-title":"Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance, 2nd ed","author":"World Health Organization","year":"2023"},{"key":"2025080104321609200_ciae614-B22","volume-title":"Update on the use of nucleic acid amplification tests to detect TB and drug-resistant TB: rapid communication","author":"World Health 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