ArticleThe New England journal of medicine2018
Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing.
Article in The New England journal of medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 2 of them syntheses that pooled it.
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Who cites it
283 citing papers in PubMed, 2 syntheses or guidelines pooled it, 517 citations in OpenAlex.
- Open-access genomic drug resistance prediction tools forJournal of clinical microbiology · 2026Pooled it
- The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2023Pooled it
- Algorithmic Determinants of Performance Heterogeneity in Whole-Genome Sequencing-Based Prediction of Drug Resistance inMicroorganisms · 2026Review
- Encoded metabolic remodeling amplifies drug resistance in Mycobacterium tuberculosis.PLoS pathogens · 2026Article
- Strain diversity drives heterogeneous responses to tuberculosis combination therapy.Antimicrobial agents and chemotherapy · 2026Article
- Reducing mapping reference and lineage bias inMicrobial genomics · 2026Article
- Whole genome sequencing for Mycobacterium tuberculosis in public health responses: a review of current practice and enablers in select low-incidence jurisdictions.BMC public health · 2026Review
- A tiled amplicon protocol for culture-free whole-genome sequencing ofJournal of clinical microbiology · 2026Article
- First insight of characteristics and prediction of Mycobacterium tuberculosis drug resistance by whole genome sequencing in Fujian Province, China.Scientific reports · 2026Article
- Tuberculosis diagnosis and the complete drug resistance pattern from a single sample within a single day by use of a composite platform of MAX MDR-TB and AmPORE-TB.Journal of clinical microbiology · 2026Article
- Interpreting antimicrobial resistance from bacterial whole-genome sequencing: prediction tools, database fragmentation, analytical trade-offs, and harmonized reporting.Frontiers in microbiology · 2026Review
- Rapid Identification of Drug-Resistant Tuberculosis Using Nanopore Targeted Next-Generation Sequencing from Sputum and Culture Isolates: Accuracy and Limitations.Infection and drug resistance · 2026Article
- Drug-resistant tuberculosis and pulmonary co-infections in immunocompromised patients: from multi-omics to precision therapy.Frontiers in microbiology · 2026Review
- Machine learning-based analysis of drug resistance mutations in Mycobacterium tuberculosis.PloS one · 2026Article
- stackPredAMR-a stacked random forest approach improves AMR phenotype prediction for multiple species and antimicrobial agents.Bioinformatics advances · 2026Article
- Extensive Endemic Transmission of Multidrug-ResistantOpen forum infectious diseases · 2026Article
- From mutation detection to treatment decisions: CRISPR-enabled diagnostics for drug-resistant tuberculosis.Frontiers in bioengineering and biotechnology · 2026Review
- Research progress on the current status of respiratory pathogen infections and their detection methods.Frontiers in microbiology · 2026Review
- Diagnostic algorithms for tuberculosis in Europe: insights from the European Reference Laboratory Network for Tuberculosis (ERLTB-Net).The Lancet regional health. Europe · 2026Review
- Evaluation of Xpert MTB/XDR and Deeplex Myc-TB for the Rapid Detection of Drug Resistance inInternational journal of microbiology · 2026Article
223 more citing papers are in PubMed but not listed here.
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92 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear.
methodsWe obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance.
resultsA total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted.
conclusionsGenotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.).
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