{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:49:14Z","timestamp":1782910154742,"version":"3.54.5"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multidrug-resistant\/rifampicin-resistant tuberculosis (MDR\/RR-TB) poses a significant threat to global tuberculosis control. Understanding drug resistance profiles, immune signatures, and their associations with treatment outcomes is critical.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 395 MDR\/RR-TB patients were enrolled. Baseline characteristics, minimum inhibitory concentrations (MICs) for multiple anti-TB drugs, plasma inflammatory cytokine levels, and treatment outcomes were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The cohort was predominantly male (69.6%), with a median age of 40\u202fyears. Pre-extensively drug-resistant (Pre-XDR-TB) accounted for 48.4%, and treatment success rate was 66.8%. Retreated patients showed significantly higher MICs for ethambutol, isoniazid, rifampicin, moxifloxacin, ofloxacin, and streptomycin (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Strong cross-resistance was observed between moxifloxacin and ofloxacin (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      =\u202f0.93,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt;\u202f0.0001). Retreated patients had lower IL-2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.035) and higher IL-12 levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.002). Unadjusted analyses identified significant associations between elevated MICs of isoniazid, moxifloxacin, ofloxacin, and streptomycin and treatment failure. After multivariable adjustment for age, sex, treatment history, and diabetes, ethambutol (aOR\u202f=\u202f1.620,\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.007) and isoniazid (aOR\u202f=\u202f1.315,\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.018) showed positive associations with treatment failure, though these did not remain significant after false discovery rate correction for multiple comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In MDR\/RR-TB patients, elevated ethambutol and isoniazid MICs were associated with treatment failure after multivariable adjustment; however, these associations were not significant after multiple comparisons correction. The potential prognostic value of quantitative MIC testing for these drugs remains to be established in future adequately powered studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1871422","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:16:35Z","timestamp":1782908195000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical characteristics, drug resistance profiles, and inflammatory cytokine signatures in newly treated versus retreated MDR\/RR-TB patients: associations with treatment outcomes"],"prefix":"10.3389","volume":"17","author":[{"given":"Yiyan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafeng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth People\u2019s Hospital of Suzhou, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1186\/s12879-025-11547-5","article-title":"Treatment outcomes for drug-resistant tuberculosis: a retrospective longitudinal study","volume":"25","author":"Akhmedullin","year":"2025","journal-title":"BMC Infect. Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1007\/s11274-023-03636-x","article-title":"Clinical manifestations and immune response to tuberculosis","volume":"39","author":"Carabal\u00ed-Isajar","year":"2023","journal-title":"World. J. Microbiol. Biotechnol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jgar.2020.12.001","article-title":"Impact of different tuberculosis history at the onset of future multidrug-resistant tuberculosis: a large, retrospective, population-based cohort study","volume":"24","author":"Cheng","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1186\/1471-2334-14-360","article-title":"Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005\u20132012","volume":"14","author":"Choi","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1093\/cid\/cix556","article-title":"Fluoroquinolone resistance mutation detection is equivalent to culture-based drug sensitivity testing for predicting multidrug-resistant tuberculosis treatment outcome: a retrospective cohort study","volume":"65","author":"Farhat","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1093\/cid\/ciy1068","article-title":"Minimum inhibitory concentrations of fluoroquinolones and pyrazinamide susceptibility correlate to clinical improvement in multidrug-resistant tuberculosis patients: a nationwide Swedish cohort study over 2 decades","volume":"69","author":"Forsman","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1186\/s12866-025-04446-x","article-title":"Key resistance-associated mutations in multidrug-resistant tuberculosis: a genomic study from Shanghai, China, with a focus on aminoglycosides","volume":"25","author":"Guo","year":"2025","journal-title":"BMC Microbiol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3346\/jkms.2011.26.1.33","article-title":"Treatment outcome and mortality among patients with multidrug-resistant tuberculosis in tuberculosis hospitals of the public sector","volume":"26","author":"Jeon","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3390\/tropicalmed8030150","article-title":"Systemic levels of pro-inflammatory cytokines and post-treatment modulation in tuberculous lymphadenitis","volume":"8","author":"Kathamuthu","year":"2023","journal-title":"Trop. Med. Infect. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1186\/s12879-020-05350-7","article-title":"Prediction of treatment failure and compliance in patients with tuberculosis","volume":"20","author":"Koo","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"E3511","DOI":"10.1093\/cid\/ciaa1509","article-title":"Genotypic resistance of pyrazinamide but not minimum inhibitory concentration is associated with longer time to sputum culture conversion in patients with multidrug-resistant tuberculosis","volume":"73","author":"Kuhlin","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3385","DOI":"10.2147\/idr.s470963","article-title":"Specific cytokines analysis incorporating latency-associated antigens differentiates Mycobacterium tuberculosis infection status: an exploratory study","volume":"17","author":"Li","year":"2024","journal-title":"Infect. Drug Resist."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0157320","DOI":"10.1128\/aac.01573-20","article-title":"Disputed rpoB mutations in mycobacterium tuberculosis and tuberculosis treatment outcomes","volume":"65","author":"Lin","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"616","DOI":"10.3967\/bes2021.085","article-title":"Evaluation of multidrug resistant loop-mediated isothermal amplification assay for detecting the drug resistance of Mycobacterium tuberculosis","volume":"34","author":"Liu","year":"2021","journal-title":"Biomed. Environ. Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1017\/s0950268820003131","article-title":"Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China","volume":"149","author":"Liu","year":"2021","journal-title":"Epidemiol. Infect."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.ijid.2020.10.081","article-title":"Acquisition of clofazimine resistance following bedaquiline treatment for multidrug-resistant tuberculosis","volume":"102","author":"Liu","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"721013","DOI":"10.3389\/fimmu.2021.721013","article-title":"Activation phenotype of Mycobacterium tuberculosis-specific CD4+ T cells promoting the discrimination between active tuberculosis and latent tuberculosis infection","volume":"12","author":"Luo","year":"2021","journal-title":"Front. Immunol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1111\/resp.13393","article-title":"Drug resistance mechanisms and drug susceptibility testing for tuberculosis","volume":"23","author":"Miotto","year":"2018","journal-title":"Respirology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/imm.12762","article-title":"Influence of diabetes mellitus on immunity to human tuberculosis","volume":"152","author":"Nathella","year":"2017","journal-title":"Immunology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"102220","DOI":"10.1016\/j.tube.2022.102220","article-title":"Pyrazinamide enhances persistence of T-cell memory induced by tuberculosis subunit vaccine LT70","volume":"135","author":"Niu","year":"2022","journal-title":"Tuberculosis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2150449","DOI":"10.1080\/21505594.2022.2150449","article-title":"Pathogenicity and virulence of Mycobacterium tuberculosis","volume":"14","author":"Rahlwes","year":"2023","journal-title":"Virulence"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/s41577-024-01124-3","article-title":"How macrophage heterogeneity affects tuberculosis disease and therapy","volume":"25","author":"Russell","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e1013992","DOI":"10.1371\/journal.ppat.1013992","article-title":"Improved immune responses and tuberculosis protection by aerosol vaccination with recombinant BCG expressing ESX-1 from Mycobacterium marinum","volume":"22","author":"Sayes","year":"2026","journal-title":"PLoS Pathog."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1093\/jac\/dkt150","article-title":"Rifampicin-resistant and rifabutin-susceptible Mycobacterium tuberculosis strains: a breakpoint artefact?","volume":"68","author":"Sch\u00f6n","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1080\/22221751.2022.2095930","article-title":"Adjunctive zoledronate + IL-2 administrations enhance anti-tuberculosis V\u03b32V\u03b42 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosis","volume":"11","author":"Shen","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"598","DOI":"10.3390\/antibiotics12030598","article-title":"Characteristics of previous tuberculosis treatment history in patients with treatment failure and the impact on acquired drug-resistant tuberculosis","volume":"12","author":"Soedarsono","year":"2023","journal-title":"Antibiotics-Basel"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1099\/jmm.0.001825","article-title":"New generation fluoroquinolone sitafloxacin could potentially overcome the majority levofloxacin and moxifloxacin resistance in multidrug-resistant Mycobacterium tuberculosis","volume":"73","author":"Sun","year":"2024","journal-title":"J. Med. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"268","DOI":"10.3855\/jidc.11974","article-title":"Characterization of katG, inhA, rpoB and pncA in Mycobacterium tuberculosis isolates from MDR-TB risk patients in Thailand","volume":"14","author":"Suthum","year":"2020","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"5275","DOI":"10.2147\/IDR.S374687","article-title":"The correlations of minimal inhibitory concentration values of anti-TB drugs with treatment outcomes and clinical profiles in patients with multidrug-resistant tuberculosis (MDR-TB) in China","volume":"15","author":"Tang","year":"2022","journal-title":"Infect Drug Resist"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"590","DOI":"10.3390\/antibiotics12030590","article-title":"Perchlozone resistance in clinical isolates of Mycobacterium tuberculosis","volume":"12","author":"Ushtanit","year":"2023","journal-title":"Antibiotics-Basel"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"102567","DOI":"10.1016\/j.tube.2024.102567","article-title":"Tuberculosis and T cells: impact of T cell diversity in tuberculosis infection","volume":"149","author":"Vats","year":"2024","journal-title":"Tuberculosis"},{"key":"ref21","volume-title":"Global Tuberculosis Report 2024","year":"2024"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1118424","DOI":"10.3389\/fcimb.2023.1118424","article-title":"The survival analysis of rifampicin\/multidrug-resistant tuberculosis patients based on the levels of inflammatory biomarkers: a retrospective cohort study","volume":"13","author":"Yu","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1871422\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:16:58Z","timestamp":1782908218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1871422\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":33,"alternative-id":["10.3389\/fmicb.2026.1871422"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1871422","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1871422"}}