Abstract
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 MTBDRsl 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.
Highlights
10 million people were infected with tuberculosis (TB) in 2019 [1]
A total of 62 archived multidrug-resistant tuberculosis (MDR-TB) isolates were included in this study
As the study aimed to investigate the frequency of the mutational patterns of gyr genes and their association with the different levels of FQ resistance among the MDR-TB patients, we randomly included a total of 62 MDR-TB isolates
Summary
10 million people were infected with tuberculosis (TB) in 2019 [1]. The main factor that limits TB control is the global spread of drug-resistant Mycobacterium tuberculosis (Mtb) isolates [2]. The high pathogenicity of drug-resistant TB (DR-TB) leads to treatment failure and increases the transmission of the disease. 3.3% of new TB cases and 18.0% of previously treated TB cases globally are multidrug-resistant (MDR). MDR-TB is defined as Mtb strains having resistance to at least rifampicin and isoniazid. MDR-TB with additional resistance to any fluoroquinolone (FQ) and at least one additional group A drug (levofloxacin, moxifloxacin, bedaquiline, and linezolid) is referred to as extensively drug-resistant TB (XDR-TB). According to the Global TB Report of 2019, the proportion of MDR-TB that developed XDR-TB was 6.2%.
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