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Research article
Abdul Rehman
University of the Punjab
Corresponding Author
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Background Flouroquinolones (FQs) are the potential drugs that inhibit DNA synthesis and used in the treatment of MDR-TB and anti-TB short term regimens. In recent year’s high proportion of flouroquinolone (FQs) resistance in Mycobacterium tuberculosis isolates has been observed. The development of FQs resistance among multidrug resistant TB (Pre-XDR TB) negatively impact patient treatment outcome and is a serious threat to control TB.
Methods A total of 562 samples were included in the study from patients with pulmonary TB which had been on anti-tuberculosis therapy. MTBDRsl assay was performed for molecular detection of mutations. Sequence analysis was performed for characterization and mutational profiling of FQ resistant isolates.
Results FQs resistance was observed in 104 (18.5%) samples and most of them were previously treated and treatment failure cases. A total of 102 isolates had mutations in gyrA gene. While gyrB gene mutations were observed in only two isolates. Mutational analysis showed that the mutations mostly alter protein at codon 94 (D94G) (represents the replacement of aspartic acid with glycine) and 90 (A90V) (substitution of alanine with valine). In MDR and treatment failure cases, the FQs-R was most commonly associated with D94G mutation. Whereas, a high proportion of A90V mutation was observed in MTB isolates which were newly diagnosed.
Conclusion The findings suggest that the genotypic studies for FQs resistance should be carried out at time of initial diagnosis, before starting treatment, to rule out all type of mutations and its potential use in the treatment and to control resistance.
Keywords
XDR-Tuberculosis, Mycobacterium tuberculosis, flouroquinolone resistance, MTBDRsl assay
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View the published article at BMC Pulmonary Medicine.
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On 13 Apr, 2020
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On 12 Apr, 2020
Editor invited
On 12 Apr, 2020
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Editorial decision: Major revision
On 17 Mar, 2020
Editor assigned
On 03 Feb, 2020
Submission checks complete
On 02 Feb, 2020
Editor invited
On 02 Feb, 2020
Version 2
Posted 15 Jan, 2020
No comments provided
Editorial decision: Minor revision
On 16 Jan, 2020
Editor assigned
On 10 Jan, 2020
Submission checks complete
On 09 Jan, 2020
Editor invited
On 09 Jan, 2020
No comments provided
Reviewer #2 agreed
On 13 Dec, 2019
Review #2 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #1 received
Received 07 Nov, 2019
Editor assigned
On 22 Oct, 2019
Reviewers invited
Invitations sent on 22 Oct, 2019
Reviewer #1 agreed
On 22 Oct, 2019
Submission checks complete
On 03 Oct, 2019
Editor invited
On 03 Oct, 2019
First submitted
On 23 Sep, 2019
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Subject Areas
Pulmonology
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A new preprint design is coming!
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See the published version of this preprint at BMC Pulmonary Medicine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Abdul Rehman
University of the Punjab
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Pulmonary Medicine.
No community comments so far
Editor assigned
On 13 Apr, 2020
Submission checks complete
On 12 Apr, 2020
Editor invited
On 12 Apr, 2020
No comments provided
Editorial decision: Major revision
On 17 Mar, 2020
Editor assigned
On 03 Feb, 2020
Submission checks complete
On 02 Feb, 2020
Editor invited
On 02 Feb, 2020
Version 2
Posted 15 Jan, 2020
No comments provided
Editorial decision: Minor revision
On 16 Jan, 2020
Editor assigned
On 10 Jan, 2020
Submission checks complete
On 09 Jan, 2020
Editor invited
On 09 Jan, 2020
No comments provided
Reviewer #2 agreed
On 13 Dec, 2019
Review #2 received
Received 13 Dec, 2019
Editorial decision: Major revision
On 13 Dec, 2019
Review #1 received
Received 07 Nov, 2019
Editor assigned
On 22 Oct, 2019
Reviewers invited
Invitations sent on 22 Oct, 2019
Reviewer #1 agreed
On 22 Oct, 2019
Submission checks complete
On 03 Oct, 2019
Editor invited
On 03 Oct, 2019
First submitted
On 23 Sep, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Pulmonary Medicine.
Background Flouroquinolones (FQs) are the potential drugs that inhibit DNA synthesis and used in the treatment of MDR-TB and anti-TB short term regimens. In recent year’s high proportion of flouroquinolone (FQs) resistance in Mycobacterium tuberculosis isolates has been observed. The development of FQs resistance among multidrug resistant TB (Pre-XDR TB) negatively impact patient treatment outcome and is a serious threat to control TB.
Methods A total of 562 samples were included in the study from patients with pulmonary TB which had been on anti-tuberculosis therapy. MTBDRsl assay was performed for molecular detection of mutations. Sequence analysis was performed for characterization and mutational profiling of FQ resistant isolates.
Results FQs resistance was observed in 104 (18.5%) samples and most of them were previously treated and treatment failure cases. A total of 102 isolates had mutations in gyrA gene. While gyrB gene mutations were observed in only two isolates. Mutational analysis showed that the mutations mostly alter protein at codon 94 (D94G) (represents the replacement of aspartic acid with glycine) and 90 (A90V) (substitution of alanine with valine). In MDR and treatment failure cases, the FQs-R was most commonly associated with D94G mutation. Whereas, a high proportion of A90V mutation was observed in MTB isolates which were newly diagnosed.
Conclusion The findings suggest that the genotypic studies for FQs resistance should be carried out at time of initial diagnosis, before starting treatment, to rule out all type of mutations and its potential use in the treatment and to control resistance.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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