ArticleBMC infectious diseases2022
Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance.
Article in BMC infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Evaluation of Xpert MTB/XDR and Deeplex Myc-TB for the Rapid Detection of Drug Resistance inInternational journal of microbiology · 2026Article
- Diagnostic algorithms for tuberculosis in Europe: insights from the European Reference Laboratory Network for Tuberculosis (ERLTB-Net).The Lancet regional health. Europe · 2026Review
- The public health utility of whole genome sequencing: Insights from a tuberculosis outbreak in Australia and perspectives of public health professionals.PLOS global public health · 2026Article
- A comprehensive evaluation of a novel targeted-sequencing workflow forFrontiers in cellular and infection microbiology · 2025Article
- Impact of isoniazid monoresistance on overall and vulnerable patient populations in Taiwan.Emerging microbes & infections · 2024Article
- Implementation of Whole Genome Sequencing of Tuberculosis Isolates in a Referral Center in Rome: Six Years' Experience in Characterizing Drug-Resistant TB and Disease Transmission.Antibiotics (Basel, Switzerland) · 2024Article
- Article
- Implementation of national whole-genome sequencing ofMicrobial genomics · 2023Article
- The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions.The Journal of clinical investigation · 2023Review
- Pyrazinamide-resistant Tuberculosis Obscured From Common Targeted Molecular Diagnostics.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Article
- Advancing tuberculosis management: the role of predictive, preventive, and personalized medicine.Frontiers in microbiology · 2023Review
- Direct detection of drug-resistantFrontiers in public health · 2023Article
- Whole genome sequencing and prediction of antimicrobial susceptibilities in non-tuberculous mycobacteria.Frontiers in microbiology · 2022Review
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Authors and funding
4 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. The WHO recommends addition of a fluoroquinolone for isoniazid mono-resistance, so early detection may be of use. The aim of this study was to describe the clinical utility and impact of WGS on treatment decisions for TB in a low incidence high resource clinical setting. The clinical turnaround time (TAT) for WGS was analysed in comparison to TB PCR using Xpert MTB/RIF (Cepheid, Sunnyvale, CA) results where available and subsequent phenotypic drug susceptibility testing (DST) when required.
methodsThis was a retrospective analysis of TB cases from January 2018 to March 2019 in London. Susceptibility and TAT by WGS, phenotypic DST, TB PCR using Xpert MTB/RIF were correlated to drug changes in order to describe the utility of WGS on treatment decisions on isoniazid mono-resistance in a low incidence high resource setting.
results189 TB cases were identified; median age 44 years (IQR 28-60), m:f ratio 112:77, 7 with HIV and 6 with previous TB. 80/189 cases had a positive culture and WGS result. 50/80 were fully sensitive to 1st line treatment on WGS, and the rest required additional DST. 20/80 cases required drug changes; 12 were defined by WGS: 8 cases had isoniazid mono-resistance, 2 had MDR-TB, 1 had isoniazid and pyrazinamide resistance and 1 had ethambutol resistance. The median TAT for positive culture was 16 days (IQR 12.5-20.5); for WGS was 35 days (IQR 29.5-38.75) and for subsequent DST was 86 days (IQR 69.5-96.75), resulting in non-WHO regimens for a median of 50.5 days (IQR 28.0-65.0). 9/12 has TB PCRs (Xpert MTB/RIF), with a median TAT of 1 day.
conclusionWGS clearly has a substantial role in our routine UK clinical settings with faster turnaround times in comparison to phenotypic DST. However, the majority of treatment changes defined by WGS were related to isoniazid resistance and given the 1 month TAT for WGS, it would be preferable to identify isoniazid resistance more quickly. Therefore if resources allow, diagnostic pathways should be optimised by parallel use of WGS and new molecular tests to rapidly identify isoniazid resistance in addition to rifampicin resistance and to minimise delays in starting WHO isoniazid resistance treatment.
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