{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:05:11Z","timestamp":1790867111173,"version":"4.1.0"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"EC | H2020 | ERA-LEARN | European and Developing Countries Clinical Trials Partnership","award":["RIA2020I-3305 CAGE-TB"],"award-info":[{"award-number":["RIA2020I-3305 CAGE-TB"]}]},{"name":"HHS | National Institutes of Health","award":["D43TW010350 U01AI152087 U54EB027049 R01AI136894"],"award-info":[{"award-number":["D43TW010350 U01AI152087 U54EB027049 R01AI136894"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,3,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Xpert MTB\/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDR\n              <jats:italic>plus<\/jats:italic>\n              . There are limited data on discordant results, including when re-tested using newer methods, like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing. MTBDR\n              <jats:italic>plus<\/jats:italic>\n              rifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads (SMOR;\n              <jats:italic>rpoB<\/jats:italic>\n              ,\n              <jats:italic>inhA<\/jats:italic>\n              ,\n              <jats:italic>katG<\/jats:italic>\n              ) on isolate DNA were done (SMOR was used as a reference standard). Between 1 April 2021 and 30 September 2022, 8% (109\/1347) of Ultra rifampicin-resistant specimens were MTBDR\n              <jats:italic>plus<\/jats:italic>\n              -susceptible. Of 89% (97\/109) isolates with a sequenceable\n              <jats:italic>rpoB<\/jats:italic>\n              , SMOR resolved most in favor of Ultra (79% [77\/97]). Sputum with lower mycobacterial load was associated with Ultra false-positive resistance (46% [11\/24] of \u201cvery low\u201d Ultra had false resistance vs 12% [9\/73;\n              <jats:italic>P<\/jats:italic>\n              = 0.0004] of \u2265\u201clow\u201d), as were Ultra heteroresistance calls (all wild-type probes, \u22651 mutant probe) (62% [23\/37 vs 25% 15\/60] for Ultra without heteroresistance calls;\n              <jats:italic>P<\/jats:italic>\n              = 0.0003). Of the 91% (88\/97) of isolates successfully tested by FT-MTBDR, 55% (48\/88) were FT-MTBDR rifampicin-resistant and 45% (40\/88) susceptible, translating to 69% (47\/68) sensitivity and 95% (19\/20) specificity. In the 91% (99\/109) of isolates with\n              <jats:italic>inhA<\/jats:italic>\n              and\n              <jats:italic>katG<\/jats:italic>\n              sequenced, 62% (61\/99) were SMOR isoniazid-susceptible. When Ultra and MTBDR\n              <jats:italic>plus<\/jats:italic>\n              rifampicin results are discordant, Ultra is more likely to be correct, and FT-MTBDR agrees more with Ultra than MTBDR\n              <jats:italic>plus<\/jats:italic>\n              ; however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra\u2013MTBDR\n              <jats:italic>plus<\/jats:italic>\n              discordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01671-24","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T14:00:45Z","timestamp":1738936845000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Xpert MTB\/RIF Ultra-resistant and MTBDR\n            <i>plus-<\/i>\n            susceptible rifampicin results in people with tuberculosis: utility of FluoroType MTBDR and deep sequencing"],"prefix":"10.1128","volume":"69","author":[{"given":"Yonas","family":"Ghebrekristos","sequence":"first","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]},{"name":"National Health Laboratory Service, Greenpoint Tuberculosis Laboratory","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysha","family":"Ahmed","sequence":"additional","affiliation":[{"name":"National Health Laboratory Service, Greenpoint Tuberculosis Laboratory","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Beylis","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Department of Pathology, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarishna","family":"Singh","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]},{"name":"National Health Laboratory Service, Greenpoint Tuberculosis Laboratory","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6676-5431","authenticated-orcid":true,"given":"Christoffel","family":"Opperman","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]},{"name":"National Health Laboratory Service, Greenpoint Tuberculosis Laboratory","place":["Cape Town, South Africa"]},{"name":"Division of Medical Microbiology, Department of Pathology, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Naufal","sequence":"additional","affiliation":[{"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Folkerts","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute","place":["Phoenix, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-059X","authenticated-orcid":true,"given":"David","family":"Engelthaler","sequence":"additional","affiliation":[{"name":"Translational Genomics Research Institute","place":["Phoenix, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Auma","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rouxjeane","family":"Venter","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghowa","family":"Booley","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, Department of Pathology, University of Cape Town","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Warren","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-2415","authenticated-orcid":false,"given":"Grant","family":"Theron","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, and SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University","place":["Cape Town, South 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Characterization of Mycobacterium tuberculosis isolates with discordant rifampicin susceptibility test results. University of Cape Town."},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(20)30123-3"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(20)30007-0"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201703-0556OC"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00888-17"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2019-0178LE"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00812-17"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126626"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00535-16"},{"key":"e_1_3_5_14_2","unstructured":"Xpert MTB\/RIF Ultra (Package Insert). 2019. 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Retrieved 25 Jul 2024."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.31.6.1435-1438.1993"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00172-6"},{"key":"e_1_3_5_20_2","volume-title":"Management of rifampicin resistant tuberculosis: a clinical reference guide","author":"Department of Health (DOH) RoSA","year":"2020","unstructured":"Department of Health (DOH) RoSA. 2020. Management of rifampicin resistant tuberculosis: a clinical reference guide. South Africa."},{"key":"e_1_3_5_21_2","volume-title":"Clinical guidelines & standard operating procedure for the implementation of the short & long DR-TB regimens for adults, adolescents and children","author":"Western Cape Department of Health","year":"2018","unstructured":"Western Cape Department of Health. 2018. Clinical guidelines & standard operating procedure for the implementation of the short & long DR-TB regimens for adults, adolescents and children. South Africa."},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa873"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac556"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01671-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01671-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T05:11:15Z","timestamp":1743743475000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01671-24"}},"subtitle":[],"editor":[{"given":"Jared A.","family":"Silverman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,5]]}},"alternative-id":["10.1128\/aac.01671-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01671-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]},"assertion":[{"value":"2024-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01671-24"}}