Bedaquiline-Resistant TB Treatment Shows Limited Success

TOPLINE:

Patients with bedaquiline-resistant tuberculosis had a significantly longer time to sustained sputum culture conversion than those with bedaquiline-susceptible tuberculosis. Only half of the patients achieved tuberculosis-free survival at 18 months, whereas nearly one fourth died.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to assess treatment outcomes in patients with bedaquiline-resistant tuberculosis at a high HIV-burden setting in South Africa between January 2018 and June 2023.
• They analyzed 82 patients (median age, 38 years; 51% women; 70% HIV positive) with rifampicin and bedaquiline-resistant tuberculosis confirmed with a sputum culture-positive Mycobacterium tuberculosis isolate on phenotypic drug susceptibility testing.
• They also enrolled an equal number of control patients with rifampicin resistant, bedaquiline-susceptible tuberculosis — matched by age, HIV status, and baseline culture status — from another study at the same facility.
• The main outcome measures were time to sputum culture conversion, a modified World Health Organization (WHO)-defined unfavorable outcome, and tuberculosis-free survival.
• Sputum culture conversion was defined as the date of the first of two sputum samples with negative M tuberculosis cultures, regardless of whether they were consecutive, and with no intervening positive culture.

TAKEAWAY:

• The median time to sustained sputum culture conversion was significantly longer in the bedaquiline-resistant group than in the bedaquiline-susceptible group (175 days vs 32 days; log-rank P < .0001).
• Overall, 67% of patients with bedaquiline-resistant tuberculosis had a WHO-defined unfavorable outcome, of which 43% accounted for treatment failure defined as absence of culture conversion by 6 months.
• Tuberculosis-free survival rates among patients with bedaquiline-resistant tuberculosis were 50% at 6 months and 52% at 18 months. Deaths were reported in 10% and 23% of patients at 6 and 18 months, respectively.
• Extended bedaquiline use in patients with bedaquiline-resistant tuberculosis was linked to reduced 18-month mortality (adjusted hazard ratio, 0.74; 95% CI, 0.62-0.88).

IN PRACTICE:

“The findings also serve as a call to action on several fronts. Chief among these is the need to access novel tuberculosis drugs that are both effective and acceptable for this population,” the authors of a linked commentary wrote.

“Compassionate use of new drugs to replace these injectable agents would be a logical place to start,” they added.

SOURCE:

The study was led by Lindokuhle Mdlenyani from the Department of Health, Eastern Cape Province, East London, South Africa, and Zahraa Mohamed from the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa. It was published online on June 18, 2025, in The Lancet Infectious Diseases.

LIMITATIONS:

The study’s generalizability was limited by its single-center design. The matched analysis was hindered by population differences in fluoroquinolone resistance and prior treatment episodes between groups. Documentation of treatment timing for bedaquiline-resistant tuberculosis was inconsistent in medical records.

DISCLOSURES:

This study received support from the South African Medical Research Council. One author was employed by the Council. Another author disclosed serving as an independent member of the drug safety monitoring board for the Bill & Melinda Gates Medical Research Institute and Otsuka Pharmaceutical trials, and another reported receiving grants from the Bill & Melinda Gates Foundation and the National Institutes of Health. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.