P076

1:Instituto Nacional de Saúde, Mozambique; 2:Research Center Borstel, Germany; 3:German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Germany; 4:4National Tuberculosis Control Program, Ministry of Health, Mozambique

Bedaquiline is currently a key drug for treating MDR/RR-TB. The WHO recently endorsed the use of new regimens based on Bedaquiline (B), Linezolid (L), Moxifloxacin (M), Levofloxacin (Lfx), Pyrazinamide (Z), Clofazimine (C), and Delamanid (D) with the 6-month BPaLM regimen as preferred option for most patients with MDR/RR-TB. In Mozambique, BDQ resistance (BDQr) rose from 03-14% from 2016-2021. Emerging evidence suggests that rising BDQr threatens overall effectiveness of rifampicin resistance (RR) treatment. Targeted next-generation-sequencing (tNGS) was performed with Deeplex®-Myc-TB assay from GenoLyse® DNA extracted from sputum submitted to National Tuberculosis Reference Laboratory in Maputo between January 2021 to April 2025. Inclusion criteria was at least isoniazid resistant (INHr) and/or RR. Drug-resistant TB (DR-TB) predictions were successfully made for 279 samples of those 240/279 (86.0%) at least RR-TB. According to tNGS 20.1% of the RR strains were fluoroquinolone resistant (FQr). 11% had an additional BDQr and were classified XDR-TB. Overall, 27% of the RR-TB samples had additional BDQr. Interestingly, 13/240 (5.4%) had the I491F rpoB mutation not detected by commercial DR-TB, out of which nine were BDQr. High rates of BDQr identified are alarming and pose a serious threat to DR-TB control efforts in Mozambique, given BDQ’s central role MDR/RR-TB treatment regimens. Notably, over 10% of RR strains were classified as XDR, further complicating the rollout of shorter BPaL-based regimens. These findings underscore the urgent need to implement tNGS, to guide the design of individualized, effective treatment regimens and prevent treatment failure and transmission of highly resistant Mycobacterium tuberculosis strains.