Publication date: Jan 21, 2025
Background: Rising prevalence of bedaquiline resistance undermines benefits from this life-saving drug for rifampicin-resistant tuberculosis (RR-TB). Despite increasing awareness, patient-level outcomes for bedaquiline-resistant TB have not been well-characterised and case management poorly defined. Methods: We conducted a retrospective cohort study with matched controls at a TB referral hospital in South Africa. Cases included patients [≥]13 years with a phenotypic bedaquiline-resistant Mycobacterium tuberculosis isolate identified between January 2018 and June 2023. Matched controls (1:1) with bedaquiline-susceptible RR-TB were selected from a prospective observational study conducted at the same facility. Primary outcomes included time to sputum culture conversion (SCC), a modified WHO-defined unfavourable outcome, and TB-free survival (alive, with SCC, and in care or treatment completed) through 18 months. Adjusted analyses used Cox proportional hazards models. Findings: Eighty-two patients with bedaquiline-resistant TB were included; 57 (70%) were HIV-positive and 17 (21%) had no prior exposure to bedaquiline or clofazimine. Bedaquiline was prescribed for 72 (88%) and meropenem (plus amoxicillin-clavulanate) for 32 (39%) after submission of the sputum sample with the first bedaquiline-resistant Mycobacterium tuberculosis isolate. At 18 months, 43 (52%) patients achieved TB-free survival; 17 (20%) failed to achieve sustained SCC, there were 19 (23%) deaths, and 50 (80%) survivors (n=63) were still on treatment. WHO treatment outcomes following treatment initiation were unfavourable in 54 (67%) patients, driven by treatment failure in 35 (43%). Median time to SCC after treatment initiation was 175 (IQR 100–254) days in the bedaquiline resistant cohort and 32 days (IQR 30–42 days) in the matched bedaquiline susceptible cohort. Baseline smear microscopy grade (HR 0{middle dot}41, 95% CI 0{middle dot}23–0{middle dot}73, p=0{middle dot}003) and bedaquiline resistance (HR 0{middle dot}06, 95% CI 0{middle dot}02–0{middle dot}23, p
Concepts | Keywords |
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Billie | Africa |
Buffalo | Bedaquiline |
Stellenbosch | Cohort |
Tuberculosis | Days |
Dot | |
Included | |
London | |
Matched | |
Middle | |
Outcomes | |
Resistant | |
Scc | |
South | |
Treatment | |
Tuberculosis |
Semantics
Type | Source | Name |
---|---|---|
drug | DRUGBANK | Bedaquiline |
disease | MESH | tuberculosis |
pathway | KEGG | Tuberculosis |
drug | DRUGBANK | Rifampicin |
disease | IDO | facility |
drug | DRUGBANK | Clofazimine |
drug | DRUGBANK | Meropenem |
drug | DRUGBANK | Amoxicillin |
drug | DRUGBANK | Clavulanic acid |
disease | MESH | treatment failure |
disease | MESH | Infectious Diseases |
disease | MESH | Infection |