Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis
Read article: Submitted by: Dr Benjamin Dickson & Dr Clare NourseQueensland Children’s Hospital, QueenslandBackground: Historically, treatment regimens for rifampicin-resistant tuberculosis were composed of 5-7 older, second-line tuberculosis drugs, including injectables that were given for 18–24 months. Since 2022, WHO recommends shorter all-oral options including 6-month BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) in adults. For children <14 years, a 9-month, seven-drug regimen has been advised, extending up to 18 months for severe disease based on observational data. This phase 3, multinational, open-label, randomised non-inferiority trial compared the traditional 18–24 month treatment with five 9-month, all-oral regimens in individuals ≥15 years with pulmonary TB, regardless of HIV status or disease severity. Experimental regimens included combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C) and pyrazinamide (Z): BLMZ, BCLLfxZ, BDLLfxZ, DCLLfxZ, DCMZ. The primary outcome was a favourable status at 73 weeks (clinical-radiologic or microbiological), with a non-inferiority margin of −12%. Main Findings: Among 754 participants, 699 were induced in the modified intention-to-treat and 562 in the per-protocol analyses. Favourable outcomes occurred in 80.7% receiving standard therapy. Three regimens (9BCLLfxZ, 9BLMZ, 9BDLLfxZ) met non-inferiority criteria in both analyses with risk differences from +4.6% to +9.8% (mITT) and −1.8% to 0.0% (PP). Grade ≥3 adverse occurred in 55–63% with one-third therapy-related. Take-home message: Three 9-month regimes (9BLMZ, 9BCLLfxZ, and 9BDLLfxZ) were non-inferior to standard therapy. Although the study excluded children < 15 years, all drugs in non-inferior regimens have paediatric formulations and are recommended regardless of age, and include pregnant women. Multiple simplified regimens are now available that can be selected based on individual characteristics, drug intolerances, interactions, resistance, and stock-outs.
