{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:51:31Z","timestamp":1786117891262,"version":"build-2736575974"},"reference-count":28,"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\/100016834","name":"Chongqing Municipal Health Commission","doi-asserted-by":"publisher","award":["2025WSJK096"],"award-info":[{"award-number":["2025WSJK096"]}],"id":[{"id":"10.13039\/100016834","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017501","name":"Science-Health Joint Medical Scientific Research Project of Chongqing","doi-asserted-by":"publisher","award":["Grants 2023MSXM107"],"award-info":[{"award-number":["Grants 2023MSXM107"]}],"id":[{"id":"10.13039\/100017501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017501","name":"Science-Health Joint Medical Scientific Research Project of Chongqing","doi-asserted-by":"publisher","award":["2024MSXM043"],"award-info":[{"award-number":["2024MSXM043"]}],"id":[{"id":"10.13039\/100017501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017501","name":"Science-Health Joint Medical Scientific Research Project of Chongqing","doi-asserted-by":"publisher","award":["2025MSXM045"],"award-info":[{"award-number":["2025MSXM045"]}],"id":[{"id":"10.13039\/100017501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017501","name":"Science-Health Joint Medical Scientific Research Project of Chongqing","doi-asserted-by":"publisher","award":["2025MSXM136"],"award-info":[{"award-number":["2025MSXM136"]}],"id":[{"id":"10.13039\/100017501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ-MSX0703"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0703"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chongqing Public Health Key Specialty (Discipline) Construction Project"},{"name":"Senior Medical Talents Programme of Chongqing for Young and Middle Aged"}],"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                      Clofazimine (CFZ) is a key drug used to treat drug-resistant tuberculosis (DR-TB), while pyrifazimine (TBI-166) is an improved riminophenazine derivative with better pharmacokinetics. However, there is a lack of data on its susceptibility and resistance in regions with a high disease burden, such as southwestern China. We compared the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      antimicrobial activities of CFZ and TBI-166 against 249 DR-TB clinical isolates (99 multidrug-resistant TB [MDR-TB] and 150 pre-extensively drug-resistant TB [pre-XDR-TB] isolates) from southwestern China. TBI-166 exhibited a concentration-dependent biphasic antimicrobial pattern compared to CFZ. TBI-166 showed significantly greater potency at low concentrations (MIC\u2085\u2080 = 0.031 \u00b5g\/mL TBI-166 vs 0.25 \u00b5g\/mL for CFZ;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), but attenuated inhibition at high concentrations (MIC\u2089\u2080 &gt; 4 \u00b5g\/mL vs 1 \u00b5g\/mL for CFZ;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). However, at high concentrations, the antibacterial effect of TBI-166 is weaker than that of CFZ (40% of TBI-166-resistant isolates have MIC &gt; 4 \u00b5g\/mL, compared to 6.67% of CFZ-resistant isolates,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Epidemiological cutoff values (ECOFFs) were 1.0 \u00b5g\/mL for CFZ and 0.25 \u00b5g\/mL for TBI-166. Based on these\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      ECOFFs, the resistance rate to TBI-166 (20.1%, 50\/249) was significantly higher than that to CFZ (6.0%, 15\/249,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.0001). Whole-genome sequencing revealed that mutations in\n                      <jats:italic toggle=\"yes\">Rv0678<\/jats:italic>\n                      were prevalent in dual-resistant isolates (10\/14) and TBI-166 monoresistant isolates (5\/40), while\n                      <jats:italic toggle=\"yes\">Rv1979c<\/jats:italic>\n                      mutations were less frequent, and no\n                      <jats:italic toggle=\"yes\">pepQ<\/jats:italic>\n                      mutations were detected. These mutations differed from known hotspots, suggesting potential novel resistance mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Drug-resistant tuberculosis (DR-TB) remains a major global health challenge, and optimizing treatments for high-burden regions like southwest China is crucial. This study is the first to detail the differential\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      activities of clofazimine (CFZ) and the novel TBI-166 against clinical DR-TB isolates from southwest China, alongside their resistance-associated genetic profiles. Findings show TBI-166 has enhanced low-concentration potency but higher resistance rates, plus novel mutations in\n                      <jats:italic toggle=\"yes\">Rv0678<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Rv1979c<\/jats:italic>\n                      linked to resistance. These insights will help refine clinical regimens for DR-TB and strengthen regional resistance surveillance, both of which are essential for controlling the spread of DR-TB in southwest China and informing treatment and surveillance strategies in other similar high-burden areas globally.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02664-25","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:04:19Z","timestamp":1783343059000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Comparative\n                    <i>in vitro<\/i>\n                    antimicrobial susceptibility profiles of clofazimine and pyrifazimine against clinical isolates of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    in southwest China"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3483-1131","authenticated-orcid":true,"given":"Ming","family":"Luo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Laboratory, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Laboratory, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Fan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Laboratory, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Dai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunusijiang","family":"Wubulikasimu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Shufu County People\u2019s Hospital","place":["Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanning","family":"Tang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/004eeze55","id-type":"ROR","asserted-by":"publisher"}],"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Laboratory, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengsen","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Laboratory, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Administration Office of the Hospital, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8177-571X","authenticated-orcid":false,"given":"Qian","family":"Cheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Clinical Research Center, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0604-6901","authenticated-orcid":false,"given":"Peibo","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04dcmpg83","id-type":"ROR","asserted-by":"publisher"}],"name":"Tuberculosis Department, Chongqing Public Health Medical Center","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","volume-title":"Global tuberculosis report 2024","author":"WHO","year":"2024","unstructured":"WHO. 2024. 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WHO consolidated guidelines on drug-resistant tuberculosis treatment. World Health Organisation, Geneva."},{"key":"e_1_3_5_10_2","first-page":"1025","article-title":"Guidelines for chemotherapy of drug-resistant tuberculosis (2019 short version)","volume":"41","author":"China Anti-Tuberculosis Association","year":"2019","unstructured":"China Anti-Tuberculosis Association. 2019. Guidelines for chemotherapy of drug-resistant tuberculosis (2019 short version). 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Preliminary study on the mechanism of action of phenazine compounds [In Chinese] Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing China"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00504-2"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-6621.2021.06.010"},{"key":"e_1_3_5_24_2","volume-title":"Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance","author":"WHO","year":"2023","unstructured":"WHO. 2023. Catalogue of mutations in Mycobacterium tuberculosis complex and their association with drug resistance. 2nd ed. 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