{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:20Z","timestamp":1792685960294,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Rifampicin-resistant tuberculosis (RR-TB) remains a major global health challenge, with delayed sputum culture conversion (SCC) predicting poor treatment outcomes. This study integrated whole-genome sequencing (WGS) and machine learning to identify clinical and genomic determinants of SCC failure in 150 RR-TB patients (2019\u20132023). Phenotypic and genotypic analysis revealed high rates of isoniazid resistance (74.0%) and\n                    <jats:italic>rpoB<\/jats:italic>\n                    mutations (97.3%, predominantly Ser450Leu), with 90% of strains belonging to Lineage 2 (Beijing family). While 64.7% achieved 2-month SCC, 18.0% remained culture-positive at 6 months. Univariate analysis linked 2-month SCC failure to smear positivity, resistance to isoniazid, amikacin, capreomycin, and levofloxacin, and pre-XDR-TB status, though only smear positivity (aOR=2.41, P=0.008) and levofloxacin resistance (aOR=2.83, P=0.003) persisted as independent predictors in multivariable analysis. A Random Forest model achieved robust prediction of SCC failure (AUC: 0.86 \u00b1 0.06 at 2 months; 0.76 \u00b1 0.10 at 6 months), identifying levofloxacin resistance (feature importance: 6.37),\n                    <jats:italic>embB<\/jats:italic>\n                    _p.Met306Ile (5.94), and smear positivity (5.12) as top 2-month predictors, while\n                    <jats:italic>katG<\/jats:italic>\n                    _p.Ser315Thr (4.85) and\n                    <jats:italic>gyrA<\/jats:italic>\n                    _p.Asp94Gly (3.43) dominated 6-month predictions. These findings underscore smear positivity, levofloxacin resistance, and specific resistance mutations as critical drivers of SCC failure, guiding targeted RR-TB treatment strategies.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2025.1641385","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T06:19:49Z","timestamp":1754547589000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Whole-genome sequencing and machine learning reveal key drivers of delayed sputum conversion in rifampicin-resistant tuberculosis"],"prefix":"10.3389","volume":"15","author":[{"given":"Qing","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junshun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1021\/bi5000564","article-title":"Mechanism of quinolone action and resistance","volume":"53","author":"Aldred","year":"2014","journal-title":"Biochemistry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1128\/AAC.01691-09","article-title":"Identification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis","volume":"54","author":"Ando","year":"2010","journal-title":"Antimicrob. 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