Off-label evaluation of the BD MAX MDR-TB assay for rapid diagnosis of rifampicin and isoniazid resistance of Mycobacterium tuberculosis clinical isolates in a high-volume reference laboratory.

Drug-resistant tuberculosis (TB) remains a primary global health concern. Multidrug-resistant TB is defined by resistance to at least rifampicin (RIF) and isoniazid (INH), the two key drugs used in TB treatment. The BD MAX Multi-Drug Resistant Tuberculosis (BD MAX) assay is a fully automated real-time PCR platform recommended by the World Health Organization for the initial diagnosis of TB and RIF and INH resistance (RIF-R and INH-R) directly from pulmonary clinical samples. This study aimed to assess the off-label performance of BD MAX in clinical M. tuberculosis complex (MTBC) isolates under routine laboratory conditions. The assay was first validated using non-tuberculous mycobacteria (NTM) and MTBC isolates with known mutations. For real-world validation, it was compared to the GenoType MTBDRplus by testing 1,440 clinical isolates prospectively. The BD MAX assay correctly excluded MTBC from all NTM cultures. Among MTBC isolates with known mutations, it identified 19 of 20 RIF-R isolates and 14 of 15 INH-R isolates. In prospective testing, BD MAX achieved 99.6% sensitivity (1,403/1,409), 96.8% specificity (30/31), and 99.5% overall accuracy (1,433/1,440) for MTBC detection. For drug resistance detection, it showed 95.2% (40/42) concordance for RIF, 96.8% (30/31) for INH, and 81.3% (13/16) for MDR when compared to MTBDRplus. Discrepancies between MTBDRplus and BD MAX included heteroresistant cases and unreportable resistance results by BD MAX due to infrequent mutations or low bacterial load. Overall, this study confirms BD MAX as an accurate and reliable tool for MTBC detection and drug resistance profiling in clinical isolates in high-volume TB laboratories.IMPORTANCEThis study highlights the importance of the BD MAX Multi-Drug Resistant Tuberculosis assay (BD MAX) applied in clinical isolates for the detection of multidrug-resistant tuberculosis (MDR-TB), i.e., Mycobacterium tuberculosis resistance to rifampicin and isoniazid. TB is a global health issue, and drug-resistant TB makes treatment more difficult, favoring transmission and disease amplification. The BD MAX platform offers a faster and more automated way to detect TB and drug resistance. The study showed that BD MAX, applied off-label in clinical isolates, accurately identified TB and resistance to rifampicin and isoniazid, with results comparable to those of the widely used line probe assay. This is significant in a high-volume laboratory because it is more straightforward and more rapid than the line probe assay. BD MAX showed some limitations, especially in detecting rare mutations and in cases of low bacterial levels. Overall, this tool could improve TB care, especially in high-volume laboratories.