Outcomes and Treatment-limiting Adverse Events of Patients Receiving BPaL and BPaL-FQ in California.

BACKGROUND: The regimen bedaquiline, pretomanid, and linezolid (BPaL), with or without moxifloxacin, is recommended for treating multidrug-resistant tuberculosis (MDR TB). We describe real-world outcomes and tolerability of BPaL, with or without fluroquinolone (BPaL-FQ) in the U.S.

METHODS: Using data collected by the California MDR TB Service for patients receiving BPaL and BPaL-FQ during 2020-2024, we analyzed favorable outcomes (cure or treatment completion), relapse, and adverse event frequency and severity.

RESULTS: Ninety-seven patients were started on any pretomanid-containing regimen during 2020-2024; 76 (78%) of these had pulmonary TB, 21 (22%) had concurrent or exclusive extrapulmonary disease. Sixty-nine patients received at least 4 weeks of BPaL or BPaL-FQ and had final outcome documented. Favorable treatment outcomes were reported in 64 (93%) patients overall and in more than 80% of patients in almost all subgroups, regardless of underlying resistance pattern, site of disease, or comorbidities. There were no microbiologically confirmed TB relapses. Two deaths occurred in patients receiving BPaL-FQ. Adverse events that led to a drug change occurred in 40% of patients and included peripheral neuropathy, cytopenias, gastrointestinal upset, and headache or dizziness. The majority were attributed to linezolid 600 mg daily and associated with linezolid trough above 2 µg/mL; fluroquinolones were also frequently implicated.

DISCUSSION: In a cohort of patients receiving BPaL or BPaL-FQ in California during 2020-2024, a majority had a favorable outcome. More than one third of patients required drug dosage change or discontinuation to complete therapy. Linezolid was the main driver of poor tolerability and regimen changes.