<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">The CRyPTIC Consortium and the 100000 Genomes Project</style></author><author><style face="normal" font="default" size="100%">Allix-Béguec, Caroline</style></author><author><style face="normal" font="default" size="100%">Irena Arandjelovic</style></author><author><style face="normal" font="default" size="100%">Lijun Bi</style></author><author><style face="normal" font="default" size="100%">Patrick Beckert</style></author><author><style face="normal" font="default" size="100%">Maryline Bonnet</style></author><author><style face="normal" font="default" size="100%">Phelim Bradley</style></author><author><style face="normal" font="default" size="100%">Andrea Cabibbe</style></author><author><style face="normal" font="default" size="100%">Irving Cancino-Muñoz</style></author><author><style face="normal" font="default" size="100%">Mark J. Caulfield</style></author><author><style face="normal" font="default" size="100%">Angkana Chaiprasert</style></author><author><style face="normal" font="default" size="100%">Daniela Cirillo</style></author><author><style face="normal" font="default" size="100%">David Clifton</style></author><author><style face="normal" font="default" size="100%">Iñaki Comas</style></author><author><style face="normal" font="default" size="100%">Derrick W Crook</style></author><author><style face="normal" font="default" size="100%">Maria R De Filippo</style></author><author><style face="normal" font="default" size="100%">Han De Neeling</style></author><author><style face="normal" font="default" size="100%">Roland Diel</style></author><author><style face="normal" font="default" size="100%">Francis A. Drobniewski</style></author><author><style face="normal" font="default" size="100%">Kiatichai Faksri</style></author><author><style face="normal" font="default" size="100%">Maha R. Farhat</style></author><author><style face="normal" font="default" size="100%">Joy Fleming</style></author><author><style face="normal" font="default" size="100%">Philip Fowler</style></author><author><style face="normal" font="default" size="100%">Tom A. Fowler</style></author><author><style face="normal" font="default" size="100%">Gao, Qian</style></author><author><style face="normal" font="default" size="100%">Jennifer Gardy</style></author><author><style face="normal" font="default" size="100%">Deborah Gascoyne-Binzi</style></author><author><style face="normal" font="default" size="100%">Ana-Luiza Gibertoni-Cruz</style></author><author><style face="normal" font="default" size="100%">Ana Gil-Brusola</style></author><author><style face="normal" font="default" size="100%">Tanya Golubchik</style></author><author><style face="normal" font="default" size="100%">Ximena Gonzalo</style></author><author><style face="normal" font="default" size="100%">Louis Grandjean</style></author><author><style face="normal" font="default" size="100%">Guangxue, He</style></author><author><style face="normal" font="default" size="100%">Jennifer L. Guthrie</style></author><author><style face="normal" font="default" size="100%">Sarah Hoosdally</style></author><author><style face="normal" font="default" size="100%">Martin Hunt</style></author><author><style face="normal" font="default" size="100%">Zamin Iqbal</style></author><author><style face="normal" font="default" size="100%">Nazir Ismail</style></author><author><style face="normal" font="default" size="100%">James Johnston</style></author><author><style face="normal" font="default" size="100%">Faisal Khanzada</style></author><author><style face="normal" font="default" size="100%">Chiea Khor</style></author><author><style face="normal" font="default" size="100%">Thomas A. Kohl</style></author><author><style face="normal" font="default" size="100%">Clare Kong</style></author><author><style face="normal" font="default" size="100%">Sam Lipworth</style></author><author><style face="normal" font="default" size="100%">Liu, Qingyun</style></author><author><style face="normal" font="default" size="100%">Gugu Maphalala</style></author><author><style face="normal" font="default" size="100%">Elena Martinez</style></author><author><style face="normal" font="default" size="100%">Vanessa Mathys</style></author><author><style face="normal" font="default" size="100%">Matthias Merker</style></author><author><style face="normal" font="default" size="100%">Paolo Miotto</style></author><author><style face="normal" font="default" size="100%">Mistry, Nerges</style></author><author><style face="normal" font="default" size="100%">David A.J. Moore</style></author><author><style face="normal" font="default" size="100%">Megan Murray</style></author><author><style face="normal" font="default" size="100%">Stefan Niemann</style></author><author><style face="normal" font="default" size="100%">Rick T.-H. Ong</style></author><author><style face="normal" font="default" size="100%">Tim E.A. Peto</style></author><author><style face="normal" font="default" size="100%">James E. Posey</style></author><author><style face="normal" font="default" size="100%">Prammananan, Therdsak</style></author><author><style face="normal" font="default" size="100%">Alexander Pym</style></author><author><style face="normal" font="default" size="100%">Camilla Rodrigues</style></author><author><style face="normal" font="default" size="100%">Mabel Rodrigues</style></author><author><style face="normal" font="default" size="100%">Timothy Rodwell</style></author><author><style face="normal" font="default" size="100%">Gian M. Rossolini</style></author><author><style face="normal" font="default" size="100%">Elisabeth Sánchez Padilla</style></author><author><style face="normal" font="default" size="100%">Marco Schito</style></author><author><style face="normal" font="default" size="100%">Xin Shen</style></author><author><style face="normal" font="default" size="100%">Jay Shendure</style></author><author><style face="normal" font="default" size="100%">Vitali Sintchenko</style></author><author><style face="normal" font="default" size="100%">Alex Sloutsky</style></author><author><style face="normal" font="default" size="100%">Grace E. Smith</style></author><author><style face="normal" font="default" size="100%">Matthew Snyder</style></author><author><style face="normal" font="default" size="100%">Karine Soetaert</style></author><author><style face="normal" font="default" size="100%">Angela M. Starks</style></author><author><style face="normal" font="default" size="100%">Supply, Philip</style></author><author><style face="normal" font="default" size="100%">Prapat Suriyapol</style></author><author><style face="normal" font="default" size="100%">Sabira Tahseen</style></author><author><style face="normal" font="default" size="100%">Patrick Tang</style></author><author><style face="normal" font="default" size="100%">Teo, Yik-Ying</style></author><author><style face="normal" font="default" size="100%">Thuong N.T. Thuong</style></author><author><style face="normal" font="default" size="100%">Guy Thwaites</style></author><author><style face="normal" font="default" size="100%">Tortoli, Enrico</style></author><author><style face="normal" font="default" size="100%">Shaheed V. Omar</style></author><author><style face="normal" font="default" size="100%">Dick van Soolingen</style></author><author><style face="normal" font="default" size="100%">Sarah A. Walker</style></author><author><style face="normal" font="default" size="100%">Timothy M. Walker</style></author><author><style face="normal" font="default" size="100%">Mark Wilcox</style></author><author><style face="normal" font="default" size="100%">Daniel J. Wilson</style></author><author><style face="normal" font="default" size="100%">David Wyllie</style></author><author><style face="normal" font="default" size="100%">Yang, Yang</style></author><author><style face="normal" font="default" size="100%">Hongtai Zhang</style></author><author><style face="normal" font="default" size="100%">Zhao, Yanlin</style></author><author><style face="normal" font="default" size="100%">Zhu, Baoli</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing</style></title><secondary-title><style face="normal" font="default" size="100%">New England Journal of MedicineNew England Journal of MedicineN Engl J Med</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018/09/26</style></date></pub-dates></dates><isbn><style face="normal" font="default" size="100%">0028-4793</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;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 pansusceptible, 3952 (97.9%) were correctly predicted.CONCLUSIONS: Genotypic 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.).&lt;/p&gt;
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