Portal de investigación
Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing
Fecha de publicación:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Allix-Beguec, C
- Arandjelovic, I
- Bi, LJ
- 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, AL
- Golubchik, T
- Gonzalo, X
- Grandjean, L
- He, GX
- Guthrie, JL
- Hoosdally, S
- Hunt, M
- Iqbal, Z
- Ismail, N
- Johnston, J
- Khanzada, FM
- Khor, CC
- Kohl, TA
- Kong, C
- Lipworth, S
- Liu, QY
- Maphalala, G
- Mathys, V
- Merker, M
- Miotto, P
- Mistry, N
- Moore, DAJ
- Murray, M
- Niemann, S
- Ong, RTH
- 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, YY
- Thuong, TNT
- Thwaites, G
- Tortoli, E
- Omar, SV
- van Soolingen, D
- Walker, AS
- Walker, TM
- Wilcox, M
- Wilson, DJ
- Wyllie, D
- Yang, Y
- Zhang, HT
- Zhao, YL
- Zhu, BL
- CRyPTIC Consortium
- 100000 Genomes Project
Grupos
Abstract
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.)
Datos de la publicación
- ISSN/ISSNe:
- 0028-4793, 1533-4406
- Tipo:
- Article
- Páginas:
- 1403-1415
- Factor de Impacto:
- 19,524 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
NEW ENGLAND JOURNAL OF MEDICINE MASSACHUSETTS MEDICAL SOC
Citas Recibidas en Web of Science: 270
Documentos
- No hay documentos
Filiaciones
Keywords
- RESISTANT TUBERCULOSIS; MULTIDRUG-RESISTANCE; XPERT MTB/RIF; TRANSMISSION; MUTATIONS; DIAGNOSIS
Proyectos asociados
BIOMARCADORES INFLAMATORIOS Y CARDÍACOS COMO PREDICTORES DE EVENTOS CARDIOVASCULARES Y MORTALIDAD TRAS EL ALTA EN LA NEUMONÍA ADQUIRIDA EN LA COMUNIDAD.
Investigador Principal: ROSARIO MENÉNDEZ VILLANUEVA
PI13/00583 . INSTITUTO DE SALUD CARLOS III . 2014
ESTUDIO EPIDEMIOLÓGICO PROSPECTIVO DE VIGILANCIA HOSPITALARIA DE LA ENFERMEDAD NEUMOCÓCICA INVASORA EN ADULTOS MAYORES DE 18 AÑOS EN ESPAÑA.
Investigador Principal: MIGUEL SALAVERT LLETÍ
PFI-PRE-2010-01 . 2012
Cita
Allix C,Arandjelovic I,Bi LJ,Beckert P,Bonnet M,Bradley P,Cabibbe AM,Cancino 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 D,Gibertoni AL,Gil A,Golubchik T,Gonzalo X,Grandjean L,He GX,Guthrie JL,Hoosdally S,Hunt M,Iqbal Z,Ismail N,Johnston J,Khanzada FM,Khor CC,Kohl TA,Kong C,Lipworth S,Liu QY,Maphalala G,Martinez E,Mathys V,Merker M,Miotto P,Mistry N,Moore D,Murray M,Niemann S,Ong RTH,Peto T,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 YY,Thuong TNT,Thwaites G,Tortoli E,Omar SV,van D,Walker AS,Walker TM,Wilcox M,Wilson DJ,Wyllie D,Yang Y,Zhang HT,Zhao YL,Zhu BL,CRyPTIC C,Genomes 100000. Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. N Engl J Med. 2018. 379. (15):p. 1403-1415. IF:70,670. (1).