Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review

The emergence and persistence of drug-resistant tuberculosis is a major threat to global public health. Our objective was to assess the applicability of whole-genome sequencing (WGS) to detect genomic markers of drug resistance and explore their association with treatment outcomes for multidrug-resi...

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Main Authors: Druti Hazra, Connie Lam, Kiran Chawla, Vitali Sintchenko, Vijay Shree Dhyani, Bhumika T. Venkatesh
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/15/12/2782
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author Druti Hazra
Connie Lam
Kiran Chawla
Vitali Sintchenko
Vijay Shree Dhyani
Bhumika T. Venkatesh
author_facet Druti Hazra
Connie Lam
Kiran Chawla
Vitali Sintchenko
Vijay Shree Dhyani
Bhumika T. Venkatesh
author_sort Druti Hazra
collection DOAJ
description The emergence and persistence of drug-resistant tuberculosis is a major threat to global public health. Our objective was to assess the applicability of whole-genome sequencing (WGS) to detect genomic markers of drug resistance and explore their association with treatment outcomes for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). Methods: Five electronic databases were searched for studies published in English from the year 2000 onward. Two reviewers independently conducted the article screening, relevant data extraction, and quality assessment. The data of the included studies were synthesized with a narrative method and are presented in a tabular format. Results: The database search identified 949 published articles and 8 studies were included. An unfavorable treatment outcome was reported for 26.6% (488/1834) of TB cases, which ranged from 9.7 to 51.3%. Death was reported in 10.5% (194/1834) of total cases. High-level fluoroquinolone resistance (due to <i>gyrA</i> 94AAC and 94GGC mutations) was correlated as the cause of unfavorable treatment outcomes and reported in three studies. Other drug resistance mutations, like kanamycin high-level resistance mutations (<i>rrs</i> 1401G), <i>rpoB</i> Ile491Phe, and <i>ethA</i> mutations, conferring prothionamide resistance were also reported. The secondary findings from this systematic review involved laboratory aspects of WGS, including correlations with phenotypic DST, cost, and turnaround time, or the impact of WGS results on public health actions, such as determining transmission events within outbreaks. Conclusions: WGS has a significant capacity to provide accurate and comprehensive drug resistance data for MDR/XDR-TB, which can inform personalized drug therapy to optimize treatment outcomes.
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spelling doaj.art-b8bb9ff6860d421d94034c78df09b3ef2023-12-22T14:32:19ZengMDPI AGPharmaceutics1999-49232023-12-011512278210.3390/pharmaceutics15122782Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic ReviewDruti Hazra0Connie Lam1Kiran Chawla2Vitali Sintchenko3Vijay Shree Dhyani4Bhumika T. Venkatesh5Department of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaSydney Institute for Infectious Diseases, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Microbiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaSydney Institute for Infectious Diseases, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, AustraliaKasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaPublic Health Evidence South Asia, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal 576104, Karnataka, IndiaThe emergence and persistence of drug-resistant tuberculosis is a major threat to global public health. Our objective was to assess the applicability of whole-genome sequencing (WGS) to detect genomic markers of drug resistance and explore their association with treatment outcomes for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). Methods: Five electronic databases were searched for studies published in English from the year 2000 onward. Two reviewers independently conducted the article screening, relevant data extraction, and quality assessment. The data of the included studies were synthesized with a narrative method and are presented in a tabular format. Results: The database search identified 949 published articles and 8 studies were included. An unfavorable treatment outcome was reported for 26.6% (488/1834) of TB cases, which ranged from 9.7 to 51.3%. Death was reported in 10.5% (194/1834) of total cases. High-level fluoroquinolone resistance (due to <i>gyrA</i> 94AAC and 94GGC mutations) was correlated as the cause of unfavorable treatment outcomes and reported in three studies. Other drug resistance mutations, like kanamycin high-level resistance mutations (<i>rrs</i> 1401G), <i>rpoB</i> Ile491Phe, and <i>ethA</i> mutations, conferring prothionamide resistance were also reported. The secondary findings from this systematic review involved laboratory aspects of WGS, including correlations with phenotypic DST, cost, and turnaround time, or the impact of WGS results on public health actions, such as determining transmission events within outbreaks. Conclusions: WGS has a significant capacity to provide accurate and comprehensive drug resistance data for MDR/XDR-TB, which can inform personalized drug therapy to optimize treatment outcomes.https://www.mdpi.com/1999-4923/15/12/2782tuberculosisdrug resistancewhole-genome sequencingdrug therapydrug treatmentmycobacterium tuberculosis
spellingShingle Druti Hazra
Connie Lam
Kiran Chawla
Vitali Sintchenko
Vijay Shree Dhyani
Bhumika T. Venkatesh
Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
Pharmaceutics
tuberculosis
drug resistance
whole-genome sequencing
drug therapy
drug treatment
mycobacterium tuberculosis
title Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
title_full Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
title_fullStr Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
title_full_unstemmed Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
title_short Impact of Whole-Genome Sequencing of <i>Mycobacterium tuberculosis</i> on Treatment Outcomes for MDR-TB/XDR-TB: A Systematic Review
title_sort impact of whole genome sequencing of i mycobacterium tuberculosis i on treatment outcomes for mdr tb xdr tb a systematic review
topic tuberculosis
drug resistance
whole-genome sequencing
drug therapy
drug treatment
mycobacterium tuberculosis
url https://www.mdpi.com/1999-4923/15/12/2782
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