ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021
Design of Multidrug-Resistant Tuberculosis Treatment Regimens Based on DNA Sequencing.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Treatment of MDR, Pre-XDR, XDR, and Rifampicin-Resistant Tuberculosis or in Case of Intolerance to at Least Rifampicin in Austria, Germany, and Switzerland.Respiration; international review of thoracic diseases · 2024Guideline
- Targeted next-generation sequencing implementation in Eswatini identifies rifampicin and bedaquiline resistance undetected by routine diagnostic testing.Nature communications · 2026Article
- Individualized Therapy Guided by Drug Susceptibility Testing for Multidrug-Resistant Tuberculosis.Open forum infectious diseases · 2026Article
- A tiled amplicon protocol for culture-free whole-genome sequencing ofJournal of clinical microbiology · 2026Article
- Genomic determinants of antibiotic resistance for Helicobacter pylori treatment: a retrospective phenotypic and genotypic observational study.The Lancet. Microbe · 2026Observational
- Performance of a broth microdilution assay for routine minimum inhibitory concentration determination of 14 anti-tuberculous drugs against theAntimicrobial agents and chemotherapy · 2025Article
- Whispers in the Wind: Face Mask Sampling for Mycobacterium tuberculosis Detection in Children With Pulmonary Tuberculosis.The Journal of infectious diseases · 2024Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Molecular determinants of multidrug-resistant tuberculosis in Sierra Leone.Microbiology spectrum · 2024Article
- Prison as a driver of recent transmissions of multidrug-resistant tuberculosis in Callao, Peru: a cross-sectional study.Lancet regional health. Americas · 2024Article
- Emerging bedaquiline-resistant tuberculosis.The Lancet. Microbe · 2023Article
- Use of High-Resolution Geospatial and Genomic Data to Characterize Recent Tuberculosis Transmission, Botswana.Emerging infectious diseases · 2023Article
- Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.The Lancet. Infectious diseases · 2023Review
- Optimizing DNA Extraction from Pediatric Stool for Diagnosis of Tuberculosis and Use in Next-Generation Sequencing Applications.Microbiology spectrum · 2023Article
- Whole-Genome Sequencing for Resistance Prediction and Transmission Analysis of Mycobacterium tuberculosis Complex Strains from Namibia.Microbiology spectrum · 2022Article
- Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study.The Lancet. Microbe · 2022Observational
- Next Generation and Other Sequencing Technologies in Diagnostic Microbiology and Infectious Diseases.Genes · 2022Review
- Clinical standards for drug-susceptible pulmonary TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2022Article
- Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance.BMC infectious diseases · 2022Article
- Whole genome sequencing-based drug resistance predictions of multidrug-resistantJAC-antimicrobial resistance · 2022Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundComprehensive and reliable drug susceptibility testing (DST) is urgently needed to provide adequate treatment regimens for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We determined whether next-generation sequencing (NGS) analysis of Mycobacterium tuberculosis complex isolates and genes implicated in drug resistance can guide the design of effective MDR/RR-TB treatment regimens.
methodsNGS-based genomic DST predictions of M. tuberculosis complex isolates from MDR/RR-TB patients admitted to a TB reference center in Germany between 1 January 2015 and 30 April 2019 were compared with phenotypic DST results of mycobacteria growth indicator tubes (MGIT). Standardized treatment algorithms were applied to design individualized therapies based on either genomic or phenotypic DST results, and discrepancies were further evaluated by determination of minimal inhibitory drug concentrations (MICs) using Sensititre MYCOTBI and UKMYC microtiter plates.
resultsIn 70 patients with MDR/RR-TB, agreement among 1048 pairwise comparisons of genomic and phenotypic DST was 86.3%; 76 (7.2%) results were discordant, and 68 (6.5%) could not be evaluated due to the presence of polymorphisms with yet unknown implications for drug resistance. Importantly, 549 of 561 (97.9%) predictions of drug susceptibility were phenotypically confirmed in MGIT, and 27 of 64 (42.2%) false-positive results were linked to previously described mutations mediating a low or moderate MIC increase. Virtually all drugs (99.0%) used in combination therapies that were inferred from genomic DST were confirmed to be susceptible by phenotypic DST.
conclusionsNGS-based genomic DST can reliably guide the design of effective MDR/RR-TB treatment regimens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.