Targeted next generation sequencing directly from sputum for comprehensive genetic information on drug resistant Mycobacterium tuberculosis.
Tuberculosis (Edinb)
; 127: 102051, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33450448
ABSTRACT
BACKGROUND:
Timely drug resistance detection is essential to global tuberculosis management. Unfortunately, rapid molecular tests assess resistance to only a few drugs, with culture required for comprehensive susceptibility test results.METHODS:
We evaluated targeted next generation sequencing (tNGS) for tuberculosis on 40 uncultured sputum samples. Resistance profiles from tNGS were compared with profiles from Xpert MTB/RIF, line probe assay (LPA), pyrosequencing (PSQ), and phenotypic testing. Concordance, sensitivity, specificity, and overall test agreement were compared across assays.RESULTS:
tNGS provided results for 39 of 40 samples (97.5%) with faster turnaround than phenotypic testing (median 3 vs. 21 days, p = 0.0068). Most samples were isoniazid and rifampin resistant (N = 31, 79.5%), 21 (53.8%) were fluoroquinolone resistant, and 3 (7.7%) were also resistant to Kanamycin. Half were of the Beijing lineage (N = 20, 51.3%). tNGS from uncultured sputum identified all resistance to isoniazid, rifampin, fluoroquinolones, and second-line injectable drugs that was identified by other methods. Agreement between tNGS and existing assays was excellent for isoniazid, rifampin, and SLDs, very good for levofloxacin, and good for moxifloxacin.CONCLUSION:
tNGS can rapidly identify tuberculosis, lineage, and drug resistance with faster turnaround than phenotypic testing. tNGS is a potential alternative to phenotypic testing in high-burden settings.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
/
DNA Bacteriano
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Técnicas Bacteriológicas
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Farmacorresistência Bacteriana
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Sequenciamento de Nucleotídeos em Larga Escala
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Pulmão
/
Mycobacterium tuberculosis
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article