{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:51:08Z","timestamp":1786117868698,"version":"build-2736575974"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100020206","name":"Health Commission of Shandong Province","doi-asserted-by":"publisher","award":["202511000739"],"award-info":[{"award-number":["202511000739"]}],"id":[{"id":"10.13039\/501100020206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010040","name":"Taishan Scholar Project of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202211358"],"award-info":[{"award-number":["tsqn202211358"]}],"id":[{"id":"10.13039\/501100010040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2025ZD01908504"],"award-info":[{"award-number":["2025ZD01908504"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Phenotypic drug susceptibility testing (pDST) for rifampicin (RIF) resistance in\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (MTB) can yield discordant results between solid and liquid culture methods, complicating accurate detection of drug-resistant tuberculosis (DR-TB). We evaluated RIF pDST concordance in 265 clinical isolates (July 2016 through June 2023) tested on Lowenstein-Jensen (L-J) medium and the Mycobacteria Growth Indicator Tube (MGIT) 960 system. Discordant isolates underwent repeat testing and whole-genome sequencing (WGS). Genotypic data were interpreted with validated pipelines. A structured literature review synthesized published data on discordant RIF phenotypes and associated\n                      <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                      variants. Overall, 11.7% (31\/265) of the isolates were discordant, with 17 L-J resistant\/MGIT-susceptible, and 14 the reverse. Discrepancies persisted on retesting in 59% (16\/27). WGS of 10 sequenced discordant isolates showed that all harbored\n                      <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                      mutations associated with rifampicin resistance, largely within the rifampicin resistance-determining region (RRDR), including Leu452Pro (5\/10) and Asp435Tyr (1\/10), plus compound patterns (Asp435Tyr + Asn437 Asp; Leu430Pro + Asn437 Asp; Met434Val + Asp435 Gly). All isolates belonged to the East Asian\/Beijing lineage and shared a synonymous\n                      <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                      Ala1075Ala; one had a synonymous\n                      <jats:italic toggle=\"yes\">rpoA<\/jats:italic>\n                      Tyr341Tyr. Putative compensatory\n                      <jats:italic toggle=\"yes\">rpoC<\/jats:italic>\n                      mutations (Lys71Asn, Glu49Gly) were detected. The literature review corroborated frequent association of Leu452Pro, Asp435Tyr, Leu430Pro, and His445 variants with inter-method discordance and previously reported low-level RIF resistance near critical concentrations. RIF pDST discordance exceeding 10% reflects inherent methodological limits and the variable phenotypic expression of specific\n                      <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                      mutations, notably Leu452Pro, which may fall below MGIT detection thresholds. In high-suspicion or phenotypically discordant cases, WGS may improve resistance classification and help inform treatment decisions and transmission control.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Accurate detection of RIF resistance underpins rapid initiation of effective TB therapy and containment of transmission. However, more than 1\/10 MTB isolates in our cohort produced reproducible, method-dependent discordance between solid (L-J) and liquid (MGIT) pDST tests. Such discordance risks misclassifying genuinely resistant strains as susceptible, especially when low-level resistance mutations (notably\n                        <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                        Leu452Pro and certain Asp435 and Leu430 variants) sit near critical concentration thresholds used in automated liquid systems. Reliance on a single phenotypic platform may therefore delay appropriate multidrug-resistant TB regimens and foster ongoing spread. Among the sequenced discordant isolates, WGS identified resistance-associated\n                        <jats:italic toggle=\"yes\">rpoB<\/jats:italic>\n                        mutations in all cases, with putative compensatory\n                        <jats:italic toggle=\"yes\">rpoC<\/jats:italic>\n                        mutations detected in some isolates, supporting its potential value as an adjudication tool. Integrating rapid genotypic methods when phenotypic results conflict, or when clinical suspicion remains high, may improve regimen selection and laboratory quality assurance.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03261-25","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:16:46Z","timestamp":1783343806000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic discordance in rifampicin resistance detection among\n                    <i>Mycobacterium tuberculosis<\/i>\n                    isolates from China: insights from whole-genome sequencing and a structured literature review"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7829-8002","authenticated-orcid":true,"given":"Ya-Li","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Lab Medicine, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]},{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Katharine Hsu International Research Center of Human Infectious Diseases, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Ping","family":"Guan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Lab Medicine, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5352-4428","authenticated-orcid":false,"given":"Yun-Feng","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Katharine Hsu International Research Center of Human Infectious Diseases, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6046-3953","authenticated-orcid":true,"given":"Mao-Shui","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Lab Medicine, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0805-8470","authenticated-orcid":true,"given":"Zhong-Fa","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207yh398","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Respiratory Medicine, Public Health Clinical Center Affiliated to Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"World Health Organization. 2025. Global tuberculosis report 2025. 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Association of Public Health Laboratories. Available from: https:\/\/www.aphl.org\/aboutAPHL\/publications\/Documents\/ID-2022-MTBC-DST-Rifampin.pdf"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.11.021"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01599-17"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.14.0651"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02422-21"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.4.1289-1294.2004"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpha.2015.11.005"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(09)70330-5"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01444"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00659-11"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.14.0297"},{"key":"e_1_3_5_33_2","unstructured":"World Health Organization. 2021. Technical report on critical concentrations for drug susceptibility testing of isoniazid and the rifamycins (rifampicin rifabutin and rifapentine). Geneva World Health Organization"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02087-21"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01086-22"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01701-23"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofv133.445"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01573-20"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01541-12"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02358-15"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03261-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.03261-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T14:39:38Z","timestamp":1786027178000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.03261-25"}},"subtitle":[],"editor":[{"given":"Michael Gordon","family":"Whitfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,4]]}},"alternative-id":["10.1128\/spectrum.03261-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.03261-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2025-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03261-25"}}