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September 17, 2020European Respiratory JournalOpen Access

Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs

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Authors

AJAgathe JouetCGCyril GaudinNBNelly Badalato

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Overview

Diagnostic study demonstrates high accuracy of targeted deep sequencing for detecting resistance to 13 anti-tuberculosis drugs in sputum samples, indicating potential for rapid tailored treatment.

Key Points

  • To evaluate the performance of a targeted deep-sequencing assay for culture-free prediction of Mycobacterium tuberculosis resistance to 13 anti-tuberculosis drugs directly from sputum samples.
  • Determined the analytical limit of detection on DNA and evaluated in silico concordance using 3,651 Mycobacterium tuberculosis complex genomes against whole-genome sequencing.
  • Tested clinical diagnostic accuracy on 429 culture isolates and validated direct culture-free application on clinical sputum specimens from Djibouti (N=109) and the Democratic Republic of the Congo (N=1,494).
  • Across 429 clinical isolates (2,369 phenotypes), the assay achieved an overall sensitivity of 95.3% and a specificity of 95.0% (95.4% and 97.1%, respectively, when excluding ethionamide).
  • Direct testing on 109 sputum samples matched culture-based whole-genome sequencing predictions with sensitivities of 93.1% to 98.5% and specificities of 95.3% to 98.5% across standard bioinformatics pipelines.
  • Direct application on 1,494 challenging sputum specimens successfully predicted 76.7% (14,902 of 19,422) of possible drug susceptibility and resistance phenotypes without bacterial culture.

Cite This Study

Jouet et al. (2020) studied this question.

synapsesocial.com/papers/6a73a14599c817e23aa73374https://doi.org/10.1183/13993003.02338-2020
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