High efficacy of BPaL among patients infected with Mycobacterium tuberculosis lineage 1 in the Philippines

BACKGROUND: (MTB) lineage 1 (L1) is less susceptible to pretomanid than other lineages, and there are limited BPaL/M efficacy data from regions where L1 is prevalent. METHODS: We performed whole genome sequencing (WGS) on baseline MTB isolates from a subgroup (34/103) of patients from the highly successful Philippine BPaL Operational Research Study to characterise their lineage and genotypic drug susceptibility testing (DST) profile. Phenotypic DST for BPaL drugs was also conducted. RESULTS: WGS analysis showed that L1 (68%) predominated, followed by L4 (26%) and L2 (6%). Out of the 22 L1 isolates tested, 20 exhibited higher pretomanid minimum inhibitory concentrations than isolates from other lineages, including one with borderline resistance. Two patients had confirmed bedaquiline resistance; no linezolid resistance was detected. All 34 patients with characterised isolates had culture converted by end of treatment. At month 12 follow-up, 30/31 patients who provided sputum remained culture negative; the single culture-positive participant harboured MTB L4. CONCLUSION: In this study, patients infected with MTB L1 responded to BPaL as well as those infected with other lineages. Baseline bedaquiline resistance was linked to the unique recurrence in the study.