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

SUMMARY BACKGROUND WHO recommends the bedaquiline–pretomanid–linezolid regimen with/without moxifloxacin (M) (BPaL/M) for the treatment of multidrug- or rifampicin-resistant TB. However, Mycobacterium tuberculosis (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.