Deeplex® Myc-TB: Targeted sequencing improves clinical detection of tuberculosis drug resistance
A recent study published in Nature Communications highlights the value of targeted next-generation sequencing (tNGS), using Deeplex® Myc-TB, in improving the clinical diagnosis of drug-resistant tuberculosis. Conducted within the national tuberculosis control programme in Eswatini, the study demonstrates that Deeplex® Myc-TB identified drug resistance mutations that are missed by conventional diagnostic methods. As a consequence, the study shows that sequencing-informed results can support treatment optimization, enabling more individualized therapeutic decisions and contributing to favorable clinical outcomes in patients with drug-resistant tuberculosis.
Comprehensive characterization of drug resistance
Unlike standard molecular tests, which interrogate a limited number of predefined mutations, Deeplex® Myc-TB simultaneously analyses 18 main gene targets involved in resistance to both first- and second-line anti-tuberculosis drugs, directly from clinical specimens. This broader approach makes it possible to detect a wider spectrum of resistance mutations to key drugs such as rifampicin and isoniazid, whose combined resistance defines multidrug-resistant tuberculosis (MDR-TB), and to core second-line drugs including bedaquiline, linezolid and fluoroquinolones, which underlie the definition of (pre-)extensively drug-resistant tuberculosis.
Hidden and emerging resistance patterns
One of the key findings of the study is the ability of tNGS to uncover resistance that escapes routine diagnostics. For rifampicin, mutations were detected in the rpoB gene, especially the I491F variant that was found in 60% of the patient specimens. This mutation is not captured by conventional diagnostic assays yet is associated with clinical resistance.
For bedaquiline, known resistance-associated mutations were also identified in Rv0678 – a key gene whose loss of function reduces susceptibility to this drug – in more than half of TB patient samples, including in 85% of rpoB I491F samples. Importantly, these mutations went also undetected by routine phenotypic testing.
Impact on clinical decisions
Beyond improved resistance detection, tNGS provided actionable information to guide treatment selection based on genotypic resistance profiles obtained directly from patients’ sputum. In the subset of 59 patients with available clinical follow-up, tNGS-informed results led to treatment modifications in 53% of cases, demonstrating its clinical utility in guiding therapy.
This diagnostic refinement was associated with favorable outcomes, with 88% of these patients achieving treatment success, highlighting the potential of sequencing-guided management to improve clinical outcomes even in complex resistance scenarios.
From molecular data to public health insight
In addition to its impact on individual patient management, the results generated by Deeplex® Myc-TB in this study highlight the potential threat posed by highly drug-resistant Mycobacterium tuberculosis strains that escape detection by conventional diagnostic tests. Sequencing-based testing can help public health programmes monitor the emergence and spread of such strains more effectively and adapt treatment and control strategies accordingly.
A confirmed clinical utility
The results of this study confirm that tNGS represents a major advance in the diagnosis of drug-resistant tuberculosis and in guiding rapid treatment decisions. Deeplex® Myc-TB is recommended by the World Health Organization (WHO). It is the only tNGS assay that meets performance criteria for ten anti-tuberculosis drugs and that is recommended by the WHO for detecting drug resistance in both drug-susceptible and multidrug-resistant/rifampicin-resistant tuberculosis.
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