Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study
The Lancet Microbe·
- DOI
- 10.1016/s2666-5247(23)00172-6
- PMID
- 37931638
- PMCID
- PMC10842724
- OpenAlex
- W4388278661
- Study type
- Cohort study
- Publisher
- Elsevier BV
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The findings demonstrate substantial bedaquiline-resistance gain in programmatically treated patients and provide evidence of bedaquiline-resistant strain transmission. The authors emphasize that routine drug susceptibility testing should urgently accompany scale-up of novel tuberculosis drugs, though rapid testing remains challenging due to genetic variant diversity.
Structured evidence summary
Research question
The study aimed to characterize bedaquiline resistance among adults with drug-resistant pulmonary tuberculosis who remained culture-positive after at least four months of bedaquiline-containing treatment.
Study design
This was a retrospective longitudinal cohort study conducted at 12 drug-resistant tuberculosis facilities in Cape Town, South Africa, from January 2016 to November 2017. Baseline and follow-up sputum isolates underwent phenotypic drug susceptibility testing, targeted deep sequencing, and whole-genome sequencing.
Population and setting
The study enrolled 40 adults aged 18 years or older with culture-positive pulmonary tuberculosis who received bedaquiline-containing regimens for at least four months in programmatic treatment settings in Cape Town, South Africa.
Main findings
Among 38 patients with assessable isolates, three had primary bedaquiline resistance, 18 gained resistance during treatment, and 17 remained susceptible throughout. Multiple genetic variants in Rv0678 and pepQ were associated with resistance. Risk factors for resistance gain included baseline fluoroquinolone resistance, clofazimine exposure, and regimens with four or fewer effective drugs. Most resistance gain resulted from acquisition, though some reinfection with resistant strains occurred.
Public-health relevance
The findings demonstrate substantial bedaquiline-resistance gain in programmatically treated patients and provide evidence of bedaquiline-resistant strain transmission. The authors emphasize that routine drug susceptibility testing should urgently accompany scale-up of novel tuberculosis drugs, though rapid testing remains challenging due to genetic variant diversity.
Important limitations
The study population represented only 40 patients from 12 facilities, which may limit generalizability. This summary is limited to the supplied single-article abstract and metadata; the original paper is required for decision-grade interpretation of methods, statistical power, and selection criteria.
GIDS interpretation
This article is discoverable through antimicrobial resistance, tuberculosis treatment, and transmission dynamics classifiers. The South African setting and genetic characterization of bedaquiline resistance variants provide context for understanding programmatic treatment challenges and the emergence of resistance to newer tuberculosis drugs.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 9 auditable classifier relationships to diseases, places, topics, and study design.