Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients

Abstract

Background: Fluoroquinolones (FQs) are potential drugs that inhibit DNA synthesis and are used in the treatment of multidrug-resistant tuberculosis (TB) and short-term anti-TB regimens. In recent years, a high proportion of FQ resistance has been observed in Mycobacterium tuberculosis isolates. The development of FQ resistance in multidrug-resistant TB negatively impacts patient treatment outcome and is a serious threat to control of TB. Methods: The study included a total of 562 samples from patients with pulmonary TB that had been on antituberculosis therapy. MTBDRsl assays were performed for the molecular detection of mutations. Sequence analysis was performed for the characterization and mutational profiling of FQ-resistant isolates. Results: FQ resistance was observed in 104 samples (18.5%), most of which were previously treated and treatment failure cases. A total of 102 isolates had mutations in DNA gyrase subunit A (gyrA), while mutations in gyrB were observed in only two isolates. Mutational analysis revealed that the mutations mostly alter codons 94 (replacing aspartic acid with glycine, D94G) and 90 (replacing alanine with valine, A90V). In MDR and treatment failure cases, resistance to FQs was most commonly associated with the D94G mutation. In contract, a high proportion of A90V mutations were observed in isolates that were newly diagnosed. Conclusion: The findings suggest that genotypic assays for FQ resistance should be carried out at the time of initial diagnosis, before starting treatment, in order to rule out mutations that impact the potential use of FQs in treatment and to control drug resistance.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas

“…Here, we identified thirteen strains harboring resistant mutation D94G in the gyr A gene. This mutation is associated with a high level of resistance to fluoroquinolones, which in consequence provides resistance to levofloxacin and moxifloxacin [ 46 ]. All thirteen isolates were genetically related and likely belonged to the same transmission network (group 6A).…”

An inexpensive, efficient and safe regimen containing Pasiniazid for MDR-TB in high Tuberculosis epidemic areas – A prospective study in China

“…As the regimen limited the patients to been not previously treated by second-line drugs including FQs, it guaranteed the sensitive rate of FQs. Therefore for patients has previously treated by FQs or had failed treatment history using FQs containing regimen, it should be cautious to select FQs as one of anti-TB regimens (23,24).…”

Variations in rifampicin and isoniazid resistance associated genetic mutations among drug naïve and recurrence cases of pulmonary tuberculosis

“…The number of AFB was counted according to the national TB program guidelines adopted from International Union against Tuberculosis and Lung Disease and World Health Organization (IUATLD/WHO) (Laboratory Diagnosis of Tuberculosis by Sputum Microscopy, 2020). Smear-negative samples were processed for culturing and DNA extraction as described by Kabir et al (2020).…”