Emergence of Specific <i>gyr</i>A Mutations Associated High-Level Fluoroquinolone-Resistant <i>Mycobacterium tuberculosis</i> among Multidrug-Resistant Tuberculosis Cases in North India

Aim: This study aims to determine the frequency and pattern of gyr A/B mutations in multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains and also to assess the association between different gyr A/B mutations with phenotypic resistance to moxifloxacin (MOX) at clinical breakpoint (CB) drug concentration. Method: A total of 106 clinical MTB isolates carrying gyr A/B mutations were included consecutively. Culture-based MOX susceptibility was tested at CB (1.0 μg/mL) followed by its correlation with gyr A/B mutations using Genotype MTBDR sl assay. The mutations associated with phenotypic resistance were further analyzed on a large dataset of 1,825 MDR tuberculosis (TB) patients. Result: D94G and A90V mutations within gyr A were significantly associated with resistance and susceptible phenotype ( p gyr 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 gyr A, gyr B, and in both the genes, respectively. D94G alone (45.9%) followed by A90V (21.2%) mutations in gyr A gene was most frequent. Conclusion: 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 gyr A mutations causing high-level FQ resistance, therefore, current control measures need to be strengthened.