Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients
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 anti-tuberculosis 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.
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Posted 16 Apr, 2020
On 13 Apr, 2020
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On 17 Mar, 2020
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On 13 Dec, 2019
Received 13 Dec, 2019
On 13 Dec, 2019
Received 07 Nov, 2019
On 22 Oct, 2019
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On 22 Oct, 2019
On 03 Oct, 2019
On 03 Oct, 2019
On 23 Sep, 2019
Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients
Posted 16 Apr, 2020
On 13 Apr, 2020
On 12 Apr, 2020
On 12 Apr, 2020
On 17 Mar, 2020
On 03 Feb, 2020
On 02 Feb, 2020
On 02 Feb, 2020
On 16 Jan, 2020
On 10 Jan, 2020
On 09 Jan, 2020
On 09 Jan, 2020
On 13 Dec, 2019
Received 13 Dec, 2019
On 13 Dec, 2019
Received 07 Nov, 2019
On 22 Oct, 2019
Invitations sent on 22 Oct, 2019
On 22 Oct, 2019
On 03 Oct, 2019
On 03 Oct, 2019
On 23 Sep, 2019
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 anti-tuberculosis 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.
Figure 1
Figure 2