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Fluoroquinolone (FQ) compounds—moxifloxacin (MOX), levofloxacin (LEV), and ofloxacin (OFL)—are used to treat multidrug-resistant tuberculosis (MDR-TB) globally. In this study, we investigated the correlation of  gyr  mutations among  Mtb  isolates with the MICs of MOX, LEV, and OFL in Bangladesh. A total of 50 MDR-TB isolates with  gyr  mutations, detected by the GenoType MTBDR sl  assay, were subjected to drug susceptibility testing to determine the MICs of the FQs. Spoligotyping was performed to correlate the genetic diversity of the gyr mutant isolates with different MIC distributions. Among the 50 isolates, 44 (88%) had mutations in the  gyrA  gene, one (2%) had a mutation in the  gyrB  gene, and five (10%) isolates had unidentified mutations. The substitutions in the  gyrA  region were at A90V ( n  = 19, 38%), D94G ( n  = 16, 32%), D94A ( n  = 4, 8%), D94N/D94Y ( n  = 4, 8%), and S91P ( n  = 1, 2%), compared to the  gyrB  gene at N538D ( n  = 1.2%). D94G mutations showed the highest MICs for MOX, LEV, and OFL, ranging between 4.0 and 8.0 μg/mL, 4.0 and 16.0 μg/mL, and 16.0 and 32.0 μg/mL, respectively; while the most common substitution of A90V showed the lowest ranges of MICs (1.0–4.0 μg/mL, 2.0–8.0 μg/mL, and 4.0–32.0 μg/mL, respectively). Spoligotyping lineages demonstrated no significant differences regarding the prevalence of different  gyr  mutations. In conclusion, the substitutions of codon A90V and D94G in the  gyr  genes were mostly responsible for the FQs’ resistance among  Mtb  isolates in Bangladesh. Low levels of resistance were associated with the substitutions of A90V, while the D94G substitutions were associated with a high level of resistance to all FQs.

pathogens

Correlation of gyr Mutations with the Minimum Inhibitory Concentrations of Fluoroquinolones among Multidrug-Resistant Mycobacterium tuberculosis Isolates in Bangladesh