{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:47:19Z","timestamp":1789660039312,"version":"4.0.1"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T00:00:00Z","timestamp":1516838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Health Innovation Challenge Fund"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rapid and accurate drug susceptibility testing (DST) is essential for the treatment of multi- and extensively drug-resistant tuberculosis (M\/XDR-TB). We compared the utility of genotypic DST assays with phenotypic DST (pDST) using Bactec 960 MGIT or L\u00f6wenstein-Jensen to construct M\/XDR-TB treatment regimens for a cohort of 25 consecutive M\/XDR-TB patients and 15 possible anti-TB drugs. Genotypic DST results from Cepheid GeneXpert MTB\/RIF (Xpert) and line probe assays (LPAs; Hain GenoType MTBDR\n            <jats:italic>plus<\/jats:italic>\n            2.0 and MTBDR\n            <jats:italic>sl<\/jats:italic>\n            2.0) and whole-genome sequencing (WGS) were translated into individual algorithm-derived treatment regimens for each patient. We further analyzed if discrepancies between the various methods were due to flaws in the genotypic or phenotypic test using MIC results. Compared with pDST, the average agreement in the number of drugs prescribed in genotypic regimens ranged from just 49% (95% confidence interval [CI], 39 to 59%) for Xpert and 63% (95% CI, 56 to 70%) for LPAs to 93% (95% CI, 88 to 98%) for WGS. Only the WGS regimens did not contain any drugs to which pDST showed resistance. Importantly, MIC testing revealed that pDST likely underestimated the true rate of resistance for key drugs (rifampin, levofloxacin, moxifloxacin, and kanamycin) because critical concentrations (CCs) were too high. WGS can be used to rule in resistance even in M\/XDR strains with complex resistance patterns, but pDST for some drugs is still needed to confirm susceptibility and construct the final regimens. Some CCs for pDST need to be reexamined to avoid systematic false-susceptible results in low-level resistant isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.01550-17","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T16:58:53Z","timestamp":1510592333000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":101,"title":["What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis"],"prefix":"10.1128","volume":"62","author":[{"given":"Jan","family":"Heyckendorf","sequence":"first","affiliation":[{"name":"Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany"},{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"International Health\/Infectious Diseases, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6nke","family":"Andres","sequence":"additional","affiliation":[{"name":"Division of Mycobacteriology (National Tuberculosis Reference Laboratory), Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-846X","authenticated-orcid":false,"given":"Claudio U.","family":"K\u00f6ser","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3392-9257","authenticated-orcid":false,"given":"Ioana D.","family":"Olaru","sequence":"additional","affiliation":[{"name":"Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany"},{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden"},{"name":"Department of Clinical and Experimental Medicine, Division of Medical Microbiology, Link\u00f6ping University, Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stureg\u00e5rd","sequence":"additional","affiliation":[{"name":"Clinical Microbiology, Department of Translational Medicine, Lund University, Malm\u00f6, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Beckert","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Schleusener","sequence":"additional","affiliation":[{"name":"Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Kohl","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Hillemann","sequence":"additional","affiliation":[{"name":"Division of Mycobacteriology (National Tuberculosis Reference Laboratory), Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danesh","family":"Moradigaravand","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-5958","authenticated-orcid":false,"given":"Julian","family":"Parkhill","sequence":"additional","affiliation":[{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Cambridge, Cambridge, United Kingdom"},{"name":"Wellcome Trust Sanger Institute, Hinxton, United Kingdom"},{"name":"London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Niemann","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9691-4741","authenticated-orcid":false,"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany"},{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"International Health\/Infectious Diseases, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"Department of Medicine, Karolinska Institute, Stockholm, Sweden"},{"name":"Department of Medicine, University of Namibia School of Medicine, Windhoek, Namibia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Merker","sequence":"additional","affiliation":[{"name":"German Center for Infection Research (DZIF), Partner site Hamburg-L\u00fcbeck-Borstel, Borstel, Germany"},{"name":"Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. 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