دورية أكاديمية
Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing
| العنوان: | Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing |
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| المؤلفون: | Allix-Beguec, C, Arandjelovic, I, Bi, L, Beckert, P, Bonnet, M, Bradley, P, Cabibbe, AM, Cancino-Munoz, I, Caulfield, MJ, Chaiprasert, A, Cirillo, DM, Clifton, D, Comas, I, Crook, DW, De Filippo, MR, De Neeling, H, Diel, R, Drobniewski, FA, Faksri, K, Farhat, MR, Fleming, J, Fowler, P, Fowler, TA, Gao, Q, Gardy, J, Gascoyne-Binzi, D, Gibertoni-Cruz, A-L, Gil-Brusola, A, Golubchik, T, Gonzalo, X, Grandjean, L, He, G, Guthrie, JL, Hoosdally, S, Hunt, M, Iqbal, Z, Ismail, N, Johnston, J, Khanzada, FM, Khor, CC, Kohl, TA, Kong, C, Lipworth, S, Liu, Q, Maphalala, G, Martinez, E, Mathys, V, Merker, M, Miotto, P, Mistry, N, Moore, DAJ, Murray, M, Niemann, S, Ong, RT-H, Peto, TEA, Posey, JE, Prammananan, T, Pym, A, Rodrigues, C, Rodrigues, M, Rodwell, T, Rossolini, GM, Padilla, ES, Schito, M, Shen, X, Shendure, J, Sintchenko, V, Sloutsky, A, Smith, EG, Snyder, M, Soetaert, K, Starks, AM, Supply, P, Suriyapol, P, Tahseen, S, Tang, P, Teo, Y-Y, Thuong, TNT, Thwaites, G, Tortoli, E, Omar, S, Van Soolingen, D, Walker, AS, Walker, TM, Wilcox, M, Wilson, DJ, Wyllie, D, Yang, Y, Zhang, H, Zhao, Y, Zhu, B |
| المصدر: | 1415 ; 1403 |
| بيانات النشر: | Massachusetts Medical Society |
| سنة النشر: | 2018 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, RESISTANT TUBERCULOSIS, MULTIDRUG-RESISTANCE, XPERT MTB/RIF, TRANSMISSION, MUTATIONS, DIAGNOSIS, Antitubercular Agents, Drug Resistance, Bacterial, Ethambutol, Genome, Genotype, Humans, Isoniazid, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Phenotype, Pyrazinamide, Rifampin, Tuberculosis, Whole Genome Sequencing, CRyPTIC Consortium and the 100,000 Genomes Project, 11 Medical And Health Sciences |
| الوصف: | Background The 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. Methods We 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. Results A 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 0028-4793 |
| العلاقة: | New England Journal of Medicine; http://hdl.handle.net/10044/1/64939Test; https://x.doi.org/10.1056/NEJMoa1800474Test |
| DOI: | 10.1056/NEJMoa1800474 |
| الإتاحة: | https://doi.org/10.1056/NEJMoa1800474Test http://hdl.handle.net/10044/1/64939Test |
| حقوق: | © 2018 Massachusetts Medical Society. All rights reserved. |
| رقم الانضمام: | edsbas.4492F469 |
| قاعدة البيانات: | BASE |
| تدمد: | 00284793 |
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| DOI: | 10.1056/NEJMoa1800474 |