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Fluoroquinolone resistance is a major challenge in treating Multidrug-Resistant Tuberculosis globally. The GenoType MTBDRsl Ver 2.0, endorsed by the WHO, was used to characterize fluoroquinolone resistance. The fluoroquinolone resistance rates in the MDR-TB, Rifampicin-Resistant TB, and non-MDR-TB were 33%, 16.5%, and 5.4%, respectively. The most common mutation found in fluoroquinolone-resistant isolates was D94G (49.5%) in the gyrA gene. Of the 150 MDR-TB isolates, the prevalence of Extensively Drug-Resistant Tuberculosis and pre-XDR-TB was 1.33% and 30%, respectively. Among the 139 RR-TB isolates, pre-XDR-TB prevalence was 15.8%. The fluoroquinolone resistance rates were 5.12% among the 1230 isoniazid-monoresistant isolates. The study found that MDR-TB and RR-TB have higher risk of fluoroquinolone resistance than non-MDR tuberculosis. Rifampicin-resistant isolates with a mutation at codon S450L have a higher risk (RR = 12.96; 95%CI: 8.34–20.13) of developing fluoroquinolone resistance than isolates with mutations at other codons in the rpoB gene. Isoniazid-resistant isolates with a mutation at codon S315T have a higher risk (RR = 2.09; 95%CI: 1.25–3.50) of developing fluoroquinolone resistance. The study concludes that rapid diagnosis of fluoroquinolone resistance before starting treatment is urgently needed to prevent the spread and increase of resistance and to achieve better treatment outcomes in areas where it is higher. [ABSTRACT FROM AUTHOR]

India accounts for about one-fourth of the global burden of MDR-TB. This study aims to assess the prevalence and factors associated with tuberculosis drug resistance among patients from South India. MTBDRplus assay and MGIT liquid culture performed on 20,245 sputum specimens obtained from presumptive MDR-TB cases during a six-year period from 2013 to 2018 were analyzed retrospectively. Univariate and multivariate logistic regression analysis was carried out to evaluate factors associated with MDR, Rifampicin mono-resistance, and Isoniazid mono-resistance. MDR, Rifampicin mono- resistant and Isoniazid mono-resistant TB were found in 5.4%, 2.5%, and 11.4% cases of presumptive MDR-TB, respectively. Based on the rpoB gene, true resistance, hetero-resistance, and inferred resistance to Rifampicin was found in 38%, 29.3%, and 32.7% of the 1582 MDR cases, respectively. S450L (MUT3) was the most common rpoB mutation present in 59.4% of the Rifampicin resistant cases. Of the 3390 Isoniazid resistant cases, 72.5% had mutations in the katG gene, and 27.5% had mutations in the inhA gene. True resistance, heteroresistance, and inferred resistance accounted for 42.9%, 22.2%, and 17.3% of the 2459 katG resistant cases, respectively. True resistance, heteroresistance, and inferred resistance for the inhA gene were found in 54.5%, 40.7%, and 4.7% cases, respectively. MDR-contact (AOR 3.171 95% CI: 1.747–5.754, p-0.000) treatment failure (AOR 2.17595% CI: 1.703–2.777, p-0.000) and female gender (AOR 1.315 95% CI: 1.117–1.548, p-0.001), were positively associated with MDR-TB. Previous TB treatment did not show a significant positive association with MDR (AOR 1.113 95% CI: 0.801–1.546, p-0.523). Old age (AOR 0.994 95% CI: 0.990–0.999, p-0.023) and HIV seropositivity (AOR 0.580 95% CI: 0.369–0.911, p-0.018) were negatively associated with MDR-TB. Although Rifampicin mono-resistance had a positive association with treatment failure (AOR 2.509 95% CI: 1.804–3.490, p <.001), it did not show any association with previous TB treatment (AOR 1.286 95% CI: 0.765–2.164, p-0.342) or with history of contact with MDR-TB (AOR 1.813 95% CI: 0.591–5.560, p-0.298). However, INH mono-resistance showed a small positive association with the previous history of treatment for TB (AOR 1.303 95% CI: 1.021–1.662, p-0.033). It was also positively associated (AOR 2.094 95% CI: 1.236–3.548, p-0.006) with MDR-TB contacts. Thus INH resistance may develop during treatment if compliance has not adhered too and may be easily passed on to the contacts while Rifampicin resistance is probably due to factors other than treatment compliance. MDR-TB, i.e. resistance to both Rifampicin and Isoniazid, is strongly correlated with treatment failure, spread through contact, and not to treatment compliance. The temporal trend in this region shows a decrease in MDR prevalence from 8.4% in 2015 to 1.3% in 2018. A similar trend is observed for Rifampicin mono-resistance and Isoniazid mono-resistance, pointing to the effectiveness of the TB control program. The higher proportion of inferred resistance observed for Rifampicin compared with INH may indicate a surfeit of mechanisms that enable rifampicin resistance. Association of MDR-TB with age, gender, and HIV status suggest the role of the immune system in the emergence of the MDR phenotype. [ABSTRACT FROM AUTHOR]

Rapid and sensitive detection of Mycobacterium tuberculosis from patient samples is vital for clinical diagnosis and treatment. The emergence of M. tuberculosis strains with either no copies or only a single copy of IS 6110 in Asian countries makes the standard PCR based diagnosis of M. tuberculosis using IS 6110 not reliable. We studied the diagnostic efficacy of the in-house PCR amplification of the candidate gene mtp40 as an alternative to IS 6110 element based diagnosis. Clinical samples included pulmonary and extra-pulmonary specimens from TB suspected patients residing in Puducherry, South India and were analyzed using in-house PCR procedures targeting IS 6110 element and mtp40 genes. Out of 317 clinical specimens analyzed, 132 (41.6 %) and 114 (36 %) were found positive for mtp40 PCR and IS 6110 PCR, respectively. However, 18 specimens that were found to negative for IS 6110 PCR were found positive for mtp40 PCR, which was further confirmed by DNA sequencing method. PCR amplification of mtp40 gene for the diagnosis of M. tuberculosis in clinical samples is fast, sensitive, and further identified clinical strains that lack IS 6110 element in this region. It is clearly demonstrated that there is a significant difference between the two PCR procedures and the sensitivity and specificity levels of mtp40 PCR were found to be higher when compared with DNA sequencing method. Thus, mtp40 based PCR technique will be beneficial in diagnosis of TB where M. tuberculosis strains lack of IS 6110 element is predominant. [ABSTRACT FROM AUTHOR]