Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing

Background: Recently, moxifloxacin (MFX)-resistant results of Mycobacterium tuberculosis (Mtb) obtained by GenoType MTBDRsl (second-line line probe assay [SL-LPA]) have been stratified to determine their resistance level; however, its accuracy has not been well studied. Therefore, the study aimed to...

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Main Authors: Raj Narayan Yadav, Manpreet Bhalla, Gavish Kumar, Grish C Sah, Ravindra Kumar Dewan, Ritu Singhal
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2022-01-01
Series:International Journal of Mycobacteriology
Subjects:
Online Access:http://www.ijmyco.org/article.asp?issn=2212-5531;year=2022;volume=11;issue=2;spage=183;epage=189;aulast=Yadav
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author Raj Narayan Yadav
Manpreet Bhalla
Gavish Kumar
Grish C Sah
Ravindra Kumar Dewan
Ritu Singhal
author_facet Raj Narayan Yadav
Manpreet Bhalla
Gavish Kumar
Grish C Sah
Ravindra Kumar Dewan
Ritu Singhal
author_sort Raj Narayan Yadav
collection DOAJ
description Background: Recently, moxifloxacin (MFX)-resistant results of Mycobacterium tuberculosis (Mtb) obtained by GenoType MTBDRsl (second-line line probe assay [SL-LPA]) have been stratified to determine their resistance level; however, its accuracy has not been well studied. Therefore, the study aimed to evaluate the diagnostic accuracy of SL-LPA, with phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS) for the detection of MFX-resistant Mtb and their resistance level. Methods: A total of 111 sputum samples were subjected to SL-LPA according to the diagnostic algorithm of the National Tuberculosis Elimination Program. Results were compared with pDST of MFX (at critical concentration [CC, 0.25 μg/ml] and clinical breakpoint [CB, 1.0 μg/ml] using BACTEC mycobacterial growth indicator tube-960), and WGS. Results: At CC, SL-LPA and pDST yielded concordant results of MFX for 104 of 111 (94%). However, at CB, 23 of 30 (77%) isolates carrying gyrA mutation known to confer low-level resistance to MFX were scored as susceptible by pDST. Among 46 Mtb isolates carrying gyrA mutations known to confer high-level resistance to MFX, 36 (78%) isolates yielded concordant results, while 10 (22%) isolates were scored as susceptible at CB by pDST. WGS identified gyrA mutations in all isolates suggested by SL-LPA. Conclusion: It is concluded that the stratification of MFX-resistant results by SL-LPA/genotypic method is not very well correlated with pDST (at CB), and hence, pDST may not be completely replaced by SL-LPA. gyrA D94G and gyrAA90V are the most prevalent mutations in MFX-resistant Mtb.
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spelling doaj.art-919515a8b75f4c2da33e4f4b70daad212022-12-22T03:00:08ZengWolters Kluwer Medknow PublicationsInternational Journal of Mycobacteriology2212-55312212-554X2022-01-0111218318910.4103/ijmy.ijmy_70_22Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencingRaj Narayan YadavManpreet BhallaGavish KumarGrish C SahRavindra Kumar DewanRitu SinghalBackground: Recently, moxifloxacin (MFX)-resistant results of Mycobacterium tuberculosis (Mtb) obtained by GenoType MTBDRsl (second-line line probe assay [SL-LPA]) have been stratified to determine their resistance level; however, its accuracy has not been well studied. Therefore, the study aimed to evaluate the diagnostic accuracy of SL-LPA, with phenotypic drug susceptibility testing (pDST) and whole-genome sequencing (WGS) for the detection of MFX-resistant Mtb and their resistance level. Methods: A total of 111 sputum samples were subjected to SL-LPA according to the diagnostic algorithm of the National Tuberculosis Elimination Program. Results were compared with pDST of MFX (at critical concentration [CC, 0.25 μg/ml] and clinical breakpoint [CB, 1.0 μg/ml] using BACTEC mycobacterial growth indicator tube-960), and WGS. Results: At CC, SL-LPA and pDST yielded concordant results of MFX for 104 of 111 (94%). However, at CB, 23 of 30 (77%) isolates carrying gyrA mutation known to confer low-level resistance to MFX were scored as susceptible by pDST. Among 46 Mtb isolates carrying gyrA mutations known to confer high-level resistance to MFX, 36 (78%) isolates yielded concordant results, while 10 (22%) isolates were scored as susceptible at CB by pDST. WGS identified gyrA mutations in all isolates suggested by SL-LPA. Conclusion: It is concluded that the stratification of MFX-resistant results by SL-LPA/genotypic method is not very well correlated with pDST (at CB), and hence, pDST may not be completely replaced by SL-LPA. gyrA D94G and gyrAA90V are the most prevalent mutations in MFX-resistant Mtb.http://www.ijmyco.org/article.asp?issn=2212-5531;year=2022;volume=11;issue=2;spage=183;epage=189;aulast=Yadavclinical breakpointcritical concentrationdrug-resistant tuberculosismoxifloxacinwhole-genome sequencing
spellingShingle Raj Narayan Yadav
Manpreet Bhalla
Gavish Kumar
Grish C Sah
Ravindra Kumar Dewan
Ritu Singhal
Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
International Journal of Mycobacteriology
clinical breakpoint
critical concentration
drug-resistant tuberculosis
moxifloxacin
whole-genome sequencing
title Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
title_full Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
title_fullStr Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
title_full_unstemmed Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
title_short Diagnostic utility of GenoType MTBDRsl assay for the detection of moxifloxacin-resistant mycobacterium tuberculosis, as compared to phenotypic method and whole-genome sequencing
title_sort diagnostic utility of genotype mtbdrsl assay for the detection of moxifloxacin resistant mycobacterium tuberculosis as compared to phenotypic method and whole genome sequencing
topic clinical breakpoint
critical concentration
drug-resistant tuberculosis
moxifloxacin
whole-genome sequencing
url http://www.ijmyco.org/article.asp?issn=2212-5531;year=2022;volume=11;issue=2;spage=183;epage=189;aulast=Yadav
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