{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:06:56Z","timestamp":1789708016013,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background: Patients with first-line drug resistance (DR) to rifampicin (RIF) or isoniazid (INH) as a first-line (FL) line probe assay (LPA) were subjected to genotypic DST using second-line (SL) LPA to identify SL-DR (including pre-XDR) under the National TB Elimination Program (NTEP), India. SL-DR patients were initiated on different DR-TB treatment regimens and monitored for their outcomes. The objective of this retrospective analysis was to understand the mutation profile and treatment outcomes of SL-DR patients. Materials and Methods: A retrospective analysis of mutation profile, treatment regimen, and treatment outcome was performed for SL-DR patients who were tested at ICMR-NIRT, Supra-National Reference Laboratory, Chennai between the years 2018 and 2020. All information, including patient demographics and treatment outcomes, was extracted from the NTEP Ni-kshay database. Results: Between 2018 and 2020, 217 patients out of 2557 samples tested were identified with SL-DR by SL-LPA. Among them, 158\/217 were FQ-resistant, 34\/217 were SLID-resistant, and 25\/217 were resistant to both. D94G (Mut3C) of gyrA and a1401g of rrs were the most predominant mutations in the FQ and SLID resistance types, respectively. Favorable (cured and treatment complete) and unfavorable outcomes (died, lost to follow up, treatment failed, and treatment regimen changed) were recorded in a total of 82\/217 and 68\/217 patients in the NTEP Ni-kshay database. Conclusions: As per the testing algorithm, SL- LPA is used for genotypic DST following identification of first-line resistance, for early detection of SL-DR in India. The fluoroquinolone resistance pattern seen in this study population corelates with the global trend. Early detection of fluoroquinolone resistance and monitoring of treatment outcome can help achieve better patient management.<\/jats:p>","DOI":"10.3390\/medicina59061005","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T01:29:26Z","timestamp":1684891766000},"page":"1005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Resistance Profiles to Second-Line Anti-Tuberculosis Drugs and Their Treatment Outcomes: A Three-Year Retrospective Analysis from South India"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8688-4617","authenticated-orcid":false,"given":"Radha","family":"Gopalaswamy","sequence":"first","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandhini","family":"Palani","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Viswanathan","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bershila","family":"Preysingh","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchithra","family":"Rajendran","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavee","family":"Vijayaraghavan","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kannadasan","family":"Thangavel","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthil Devi","family":"Vadivel","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Stanley","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-1094","authenticated-orcid":false,"given":"Kannan","family":"Thiruvengadam","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"Jayabal","sequence":"additional","affiliation":[{"name":"District TB, Chennai 600056, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleeswari","family":"Murugesan","sequence":"additional","affiliation":[{"name":"District TB, Kancheepuram 631502, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Rathinam","sequence":"additional","affiliation":[{"name":"GHTM, Tambaram, Chennai 600047, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Frederick","sequence":"additional","affiliation":[{"name":"State TB, Sathumadural 600006, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gomathi","family":"Sivaramakrishnan","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-4595","authenticated-orcid":false,"given":"Chandrasekaran","family":"Padmapriyadarsini","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakumar","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,23]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, November 01). Global TB Report, Available online: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports\/global-tuberculosis-report-2022."},{"key":"ref_2","unstructured":"WHO (2022, December 01). WHO Consolidated Guidelines on Tuberculosis. Module 4: Treatment\u2014Drug-Resistant Tuberculosis Treatment, 2022 Update, Available online: https:\/\/www.who.int\/publications-detail-redirect\/9789240063129#:~:text=Download%20(1.5%20MB)-,Overview,TB%20(DR%2DTB)."},{"key":"ref_3","unstructured":"WHO (2022, November 01). Line Probe Assays (LPA) for Detection of Drug-Resistant Tuberculosis: Interpretation and Reporting Manual for Laboratory Staff and Clinicians, Available online: https:\/\/stoptb.org\/wg\/gli\/assets\/documents\/GLI%20LPA%20selection%20manual%202022.pdf."},{"key":"ref_4","unstructured":"Division, C.T. (2022, November 01). Guideline for PMDT in India 2017, Available online: https:\/\/tbcindia.gov.in\/index1.php?lang=1&level=2&sublinkid=4780&lid=3306."},{"key":"ref_5","unstructured":"Division, C.T. (2022, November 01). Guidelines for Programmatic Management of Drug Resistant Tuberculosis in India, Available online: https:\/\/tbcindia.gov.in\/index1.php?lang=1&level=1&sublinkid=4150&lid=2794."},{"key":"ref_6","unstructured":"Division, C.T. (2022, November 01). India TB Report. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241565714."},{"key":"ref_7","unstructured":"Division, C.T. (2022, November 01). India TB Report, Available online: https:\/\/tbcindia.gov.in\/showfile.php?lid=3538."},{"key":"ref_8","unstructured":"Division, C.T. (2022, November 01). India TB Report, Available online: https:\/\/tbcindia.gov.in\/showfile.php?lid=3587."},{"key":"ref_9","unstructured":"Division, C.T. (2022, November 01). India TB Report, Available online: https:\/\/tbcindia.gov.in\/index1.php?lang=1&level=1&sublinkid=4160&lid=2807."},{"key":"ref_10","unstructured":"Division, C.T. (2023, March 01). India TB Report, Available online: https:\/\/tbcindia.gov.in\/showfile.php?lid=3680."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/trstmh\/trz121","article-title":"Burden of baseline resistance of Mycobacterium tuberculosis to fluoroquinolones and second-line injectables in central India","volume":"114","author":"Desikan","year":"2020","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mujuni, D., Kasemire, D.L., Ibanda, I., Kabugo, J., Nsawotebba, A., Phelan, J.E., Majwala, R.K., Tugumisirize, D., Nyombi, A., and Orena, B. (2022). Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: A two and a half-year\u2019s review. BMC Infect. Dis., 22.","DOI":"10.1186\/s12879-022-07339-w"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1089\/mdr.2018.0268","article-title":"Robustness of the Line Probe Assay for the Rapid Diagnosis and Characterization of Mutations in Extensively Drug-Resistant Tuberculosis","volume":"25","author":"Ninan","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Oudghiri, A., Karimi, H., Chetioui, F., Zakham, F., Bourkadi, J.E., Elmessaoudi, M.D., Laglaoui, A., Chaoui, I., and El Mzibri, M. (2018). Molecular characterization of mutations associated with resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients from high prevalence tuberculosis city in Morocco. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3009-9"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2991\/jegh.k.191215.003","article-title":"Second-line Drug Resistance Characterization in Mycobacterium tuberculosis by Genotype MTBDRsl Assay","volume":"10","author":"Sethi","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12941-021-00463-6","article-title":"Direct detection of resistance to fluoroquinolones\/SLIDs in sputum specimen by GenoType MTBDRsl v.2.0 assay A study from Eastern Uttar Pradesh, India","volume":"20","author":"Singh","year":"2021","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4103\/ijmy.ijmy_70_22","article-title":"Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing","volume":"11","author":"Yadav","year":"2022","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"446","DOI":"10.5588\/ijtld.21.0455","article-title":"Trends in rifampicin and isoniazid resistance in patients with presumptive TB","volume":"26","author":"Palani","year":"2022","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_19","unstructured":"Group, T.A. (2022, November 01). 2022 Pipeline Report. Available online: https:\/\/www.treatmentactiongroup.org\/resources\/pipeline-report\/2022-pipeline-report\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1128\/JCM.01865-16","article-title":"Evaluation of the GenoType MTBDRsl Version 2.0 Assay for Second-Line Drug Resistance Detection of Mycobacterium tuberculosis Isolates in South Africa","volume":"55","author":"Gardee","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01550-17","DOI":"10.1128\/AAC.01550-17","article-title":"What Is Resistance? Impact of Phenotypic versus Molecular Drug Resistance Testing on Therapy for Multi- and Extensively Drug-Resistant Tuberculosis","volume":"62","author":"Heyckendorf","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jinf.2018.06.014","article-title":"Multi-center evaluation of GenoType MTBDRsl line probe assay for rapid detection of pre-XDR and XDR Mycobacterium tuberculosis in China","volume":"77","author":"Gao","year":"2018","journal-title":"J. Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1089\/mdr.2020.0240","article-title":"Emergence of Specific gyrA Mutations Associated High-Level Fluoroquinolone-Resistant Mycobacterium tuberculosis among Multidrug-Resistant Tuberculosis Cases in North India","volume":"27","author":"Singh","year":"2021","journal-title":"Microb. Drug Resist."},{"key":"ref_24","unstructured":"NIRT (2022, November 01). Indian Catalogue of Mycobacterium tuberculosis Mutations and Their Association with Drug Resistance. Available online: https:\/\/www.nirt.res.in\/pdf\/Indian%20Mutation%20Catalogue%202022.pdf."},{"key":"ref_25","unstructured":"WHO (2022, November 01). Catalogue of Mutations in Mycobacterium tuberculosis Complex and Their Association with Drug Resistance, Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240028173."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/jor2010001","article-title":"Risk Factors and Treatment Outcome Analysis Associated with Second-Line Drug-Resistant Tuberculosis","volume":"2","author":"Aaina","year":"2022","journal-title":"J. Respir."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jgar.2020.11.011","article-title":"Fluroquinolone drug resistance among MDR-TB patients increases the risk of unfavourable interim microbiological treatment outcome: An observational study","volume":"24","author":"Singh","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijtb.2019.02.009","article-title":"Initial experience of bedaquiline implementation under the National TB Programme at NITRD, Delhi, India","volume":"66","author":"Sarin","year":"2019","journal-title":"Indian J. Tuberc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105956","DOI":"10.1016\/j.rmed.2020.105956","article-title":"Interim treatment outcomes in multidrug-resistant tuberculosis using bedaquiline and\/or delamanid in South Korea","volume":"167","author":"Kang","year":"2020","journal-title":"Respir. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1164\/rccm.202001-0135OC","article-title":"Culture Conversion in Patients Treated with Bedaquiline and\/or Delamanid. A Prospective Multicountry Study","volume":"203","author":"Franke","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.pulmoe.2021.02.006","article-title":"Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort","volume":"27","author":"Koirala","year":"2021","journal-title":"Pulmonology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"ofab615","DOI":"10.1093\/ofid\/ofab615","article-title":"Increased Moxifloxacin Dosing Among Patients with Multidrug-Resistant Tuberculosis with Low-Level Resistance to Moxifloxacin Did Not Improve Treatment Outcomes in a Tertiary Care Center in Mumbai, India","volume":"9","author":"Tornheim","year":"2022","journal-title":"Open Forum Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2165\/00003495-200059010-00010","article-title":"Moxifloxacin: A review of its clinical potential in the management of community-acquired respiratory tract infections","volume":"59","author":"Balfour","year":"2000","journal-title":"Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"363","DOI":"10.2165\/00003495-199957030-00007","article-title":"Moxifloxacin","volume":"57","author":"Balfour","year":"1999","journal-title":"Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1517\/14656566.9.10.1755","article-title":"Moxifloxacin: A respiratory fluoroquinolone","volume":"9","author":"Miravitlles","year":"2008","journal-title":"Expert Opin. Pharmacother."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1005\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:40:34Z","timestamp":1760125234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/6\/1005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,23]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["medicina59061005"],"URL":"https:\/\/doi.org\/10.3390\/medicina59061005","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,23]]}}}