Emergence of Specific gyrA Mutations Associated High-Level Fluoroquinolone-Resistant Mycobacterium tuberculosis among Multidrug-Resistant Tuberculosis Cases in North India.

Aim: This study aims to determine the frequency and pattern of gyrA/B mutations in multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains and also to assess the association between different gyrA/B mutations with phenotypic resistance to moxifloxacin (MOX) at clinical breakpoint (CB) drug concentration. Method: A total of 106 clinical MTB isolates carrying gyrA/B mutations were included consecutively. Culture-based MOX susceptibility was tested at CB (1.0 μg/mL) followed by its correlation with gyrA/B mutations using Genotype MTBDRsl 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 gyrA were significantly associated with resistance and susceptible phenotype (p < 0.001), respectively. Of 1,825 MDR patients, gyrA/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 gyrA, gyrB, and in both the genes, respectively. D94G alone (45.9%) followed by A90V (21.2%) mutations in gyrA 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 gyrA mutations causing high-level FQ resistance, therefore, current control measures need to be strengthened.