{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:30:15Z","timestamp":1788993015025,"version":"build-2803163510"},"reference-count":20,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2021,5]]},"abstract":"\n Aim:<\/jats:title>\n \n This study aims to determine the frequency and pattern of\n gyr<\/jats:italic>\n A\/B mutations in multidrug-resistant (MDR)\n Mycobacterium tuberculosis<\/jats:italic>\n (MTB) strains and also to assess the association between different\n gyr<\/jats:italic>\n A\/B mutations with phenotypic resistance to moxifloxacin (MOX) at clinical breakpoint (CB) drug concentration.\n <\/jats:p>\n <\/jats:sec>\n \n Method:<\/jats:title>\n \n A total of 106 clinical MTB isolates carrying\n gyr<\/jats:italic>\n A\/B mutations were included consecutively. Culture-based MOX susceptibility was tested at CB (1.0\u2009\u03bcg\/mL) followed by its correlation with\n gyr<\/jats:italic>\n A\/B mutations using Genotype MTBDR\n sl<\/jats:italic>\n assay. The mutations associated with phenotypic resistance were further analyzed on a large dataset of 1,825 MDR tuberculosis (TB) patients.\n <\/jats:p>\n <\/jats:sec>\n \n Result:<\/jats:title>\n \n D94G and A90V mutations within\n gyr<\/jats:italic>\n A were significantly associated with resistance and susceptible phenotype (\n p<\/jats:italic>\n \u2009<\u20090.001), respectively. Of 1,825 MDR patients,\n gyr<\/jats:italic>\n A\/B mutations were found in 58.8% cases, of which fluoroquinolone (FQ) resistance was concluded among 97.9%, 0.8%, and 1.3% patients due to mutation in\n gyr<\/jats:italic>\n A,\n gyr<\/jats:italic>\n B, and in both the genes, respectively. D94G alone (45.9%) followed by A90V (21.2%) mutations in\n gyr<\/jats:italic>\n A gene was most frequent.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Our study showed that MDR-TB has emerged in northern India with additional FQ resistance. Different selection pressure and transmission may result in prevailing accumulation of specific\n gyr<\/jats:italic>\n A mutations causing high-level FQ resistance, therefore, current control measures need to be strengthened.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/mdr.2020.0240","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T14:42:51Z","timestamp":1601390571000},"page":"647-651","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Emergence of Specific\n gyr<\/i>\n A Mutations Associated High-Level Fluoroquinolone-Resistant\n Mycobacterium tuberculosis<\/i>\n among Multidrug-Resistant Tuberculosis Cases in North India"],"prefix":"10.1177","volume":"27","author":[{"given":"Pravin Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Microbiology, King George's Medical University, Lucknow, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urmila","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, King George's Medical University, Lucknow, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Microbiology, King George's Medical University, Lucknow, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"Switzerland","article-title":"Global tuberculosis report 2019","author":"World Health Organization","year":"2019","unstructured":"World Health Organization. 2019. Global tuberculosis report 2019. WHO,, Geneva, Switzerland.","journal-title":"WHO,"},{"key":"e_1_3_4_3_2","first-page":"Switzerland","article-title":"WHO consolidated guidelines on drug-resistant tuberculosis treatment","author":"World Health Organization","year":"2019","unstructured":"World Health Organization. 2019. WHO consolidated guidelines on drug-resistant tuberculosis treatment. WHO,, Geneva, Switzerland.","journal-title":"WHO,"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr566"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/jac\/dkv360","article-title":"Specific gyrA gene mutations predict poor treatment outcome in MDR-TB","volume":"71","author":"Rigouts L.","year":"2016","unstructured":"Rigouts L., , Coeck N., , Gumusboga M., , de Rijk W.B, , Aung K.J.M, , Hossain M.A, , Fissette K., , Rieder H.L, , Meehan C.J, , de Jong B.C, , and Van Deun A.. 2016. Specific gyrA gene mutations predict poor treatment outcome in MDR-TB. J. Antimicrob Chemother. 71:314\u2013323.","journal-title":"J. Antimicrob Chemother"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1128\/JCM.02775-15","article-title":"Gyrase mutations are associated with variable levels of fluoroquinolone resistance in Mycobacterium tuberculosis","volume":"54","author":"Farhat M.R.","year":"2016","unstructured":"Farhat M.R., , Jacobson K.R, , Franke M.F, , Kaur D., , Sloutsky A., , Mitnick C.D, , and Murray M.. 2016. Gyrase mutations are associated with variable levels of fluoroquinolone resistance in Mycobacterium tuberculosis. J. Clin. Microbiol. 54:727\u2013733.","journal-title":"J. Clin. Microbiol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.5588\/ijtld.14.0100","article-title":"Successful \u201c9-month Bangladesh regimen\u201d for multidrug-resistant tuberculosis among over 500 consecutive patients","volume":"18","author":"Aung K.J.M.","year":"2014","unstructured":"Aung K.J.M., , Van Deun A., , Declercq E., , Sarker M.R, , Das P.K, , Hossain M.A, , and Rieder H.L.. 2014. Successful \u201c9-month Bangladesh regimen\u201d for multidrug-resistant tuberculosis among over 500 consecutive patients. Int. J Tuberc Lung Dis. 18:1180\u20131187.","journal-title":"Int. J Tuberc Lung Dis"},{"key":"e_1_3_4_8_2","first-page":"Switzerland","article-title":"Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis","author":"World Health Organization","year":"2018","unstructured":"World Health Organization. 2018. Technical Report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. WHO,, Geneva, Switzerland.","journal-title":"WHO,"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01354-2017"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"419","DOI":"10.5588\/ijtld.17.0663","volume":"22","author":"Yadav R.","year":"2018","unstructured":"Yadav R., , Saini A., , Kaur P., , Behera D., , and Sethi S.. 2018. Diagnostic accuracy of GenoType\u00ae MTBDRsl VER 2.0 in detecting second-line drug resistance to M. tuberculosis. Int. J. Tuberc. Lung Dis. 22:419\u2013424.","journal-title":"J. Tuberc. Lung Dis"},{"key":"e_1_3_4_11_2","first-page":"Switzerland","article-title":"The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs: policy guidance","author":"World Health Organization","year":"2016","unstructured":"World Health Organization. 2016. The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs: policy guidance. WHO,, Geneva, Switzerland.","journal-title":"WHO,"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.3201\/eid2509.190105","article-title":"Limited scope of shorter drug regimen for MDR TB caused by high resistance to fluoroquinolone","volume":"25","author":"Singh P.K.","year":"2019","unstructured":"Singh P.K., , and Jain A.. 2019. Limited scope of shorter drug regimen for MDR TB caused by high resistance to fluoroquinolone. Emerg. Infect. Dis. 25:1760.","journal-title":"Emerg. Infect. 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PLoS One, 10:e0120470.","journal-title":"PLoS One"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/emi.2014.21","article-title":"Association of gyrA\/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis","volume":"3","author":"Li J.","year":"2014","unstructured":"Li J., , Gao X., , Luo T., , Wu J., , Sun G., , Liu Q., , Jiang Y., , Zhang Y., , Mei J., , and Gao Q.. 2014. Association of gyrA\/B mutations and resistance levels to fluoroquinolones in clinical isolates of Mycobacterium tuberculosis. Emerg. Microb. Infect. 3:1\u20135.","journal-title":"Emerg. Microb. 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Tuberculosis, 95:137\u2013141.","journal-title":"Tuberculosis"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/emph\/eot003","article-title":"Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis","volume":"2013","author":"Borrell S.","year":"2013","unstructured":"Borrell S., , Teo Y., , Giardina F., , Streicher E.M, , Klopper M., , Feldmann J., , M\u00fcller B., , Victor T.C, , and Gagneux S.. 2013. Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis. Evol. Med. Public Health. 2013:65\u201374.","journal-title":"Evol. Med. 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Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: enhancing drug activity against wild-type and resistant gyrase. Pros. Natl. Acad. Sci. USA. 113:E839\u2013E846.","journal-title":"Pros. Natl. Acad. Sci. 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