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dc.contributor.authorMiotto, Paoloes_ES
dc.contributor.authorComas, Iñakies_ES
dc.contributor.authorRodwell, Timothy C.es_ES
dc.identifier.citationEuropean Respiratory Journal 50(6): 1701354 (2017)es_ES
dc.descriptionMiotto, Paolo. et al. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis. Eur Respir J 2017; 50: 1701354. [https://doi.org/10.1183/13993003.01354-2017]. 13 páginas, 2 figuras, 4 tablas.es_ES
dc.description.abstractA clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype-phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6-90.9%), while for isoniazid it was 78.2% (77.4-79.0%) and their specificities were 96.3% (95.7-96.8%) and 94.4% (93.1-95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1-70.6%) for capreomycin to 88.2% (85.1-90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1-92.5%) for moxifloxacin to 99.5% (99.0-99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors of M. tuberculosis drug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.es_ES
dc.description.sponsorshipThis study was supported by tEhe Bill and Melinda Gates Foundation under grant agreement FIND OPP1115209 to address how to score mutations in the ReSeqTB data sharing platform initiative. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. K. Dheda is supported by the South African MRC and the EDCTP. I. Comas is supported by the Ministerio de Economía y Competitividad (Spanish Government) research grant SAF2016–77346-R and the European Research Council (ERC) (638553-TB-ACCELERATE). L. Chindelevitch is supported by a Sloan Fellowship. S. Niemann is supported by grants of the German Center for Infection Research. Funding information for this article has been deposited with the Crossref Funder Registry.es_ES
dc.publisherEuropean Respiratory Societyes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.titleA standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosises_ES
dc.description.peerreviewedPeer reviewedes_ES
dc.rights.licenseCreative Commons Attribution Licence 4.0.es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderEuropean Research Counciles_ES
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