ArticleResearch square2026
Bedaquiline and linezolid resistance in people with rifampicin-resistant tuberculosis in the Western Cape Province of South Africa.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: South Africa was an early implementer of bedaquiline and linezolid for drug-resistant tuberculosis (TB), however, programmatic capacity for drug susceptibility testing (DST) was not initially available. Methods: We analysed people with rifampicin-resistant (RR)-TB (n=3138) programmatically tested with Xpert MTB/XDR and bedaquiline and linezolid phenotypic (p)DST in the same episode for diagnosis or treatment monitoring. Data from respiratory specimens collected 01/01/2023-31/12/2024 across six districts in Western Cape, South Africa, were included. Findings: 89% (2799/3138) of people were successfully tested with Xpert MTB/XDR, with 12% (332/2799) fluoroquinolone-resistant. 77% (2423/3138) successfully underwent bedaquiline pDST, with 12% (278/2423) resistant. 84% (232/278) of bedaquiline resistance was in the diagnostic (first) isolate. Of these, 51% (118/232) had no prior DR-TB (45 prior drug-susceptible TB, 73 no prior TB). We did not identify associations with bedaquiline-resistance, other than residence in Cape Town (OR 1.61, 1.19-2.20) and resistance to other drugs (fluoroquinolone resistance the strongest; OR 4.38, 3.20-5.96). In people initially bedaquiline-susceptible with a later isolate tested, 22% (45/201) gained resistance. Bedaquiline-resistance was most frequent in the Overberg region [14% (8, 23) of RR/MDR-TB]. 86% (2411/2799) of people had a successful linezolid pDST, with <1% (2/2411) resistant. All 128 people with repeat linezolid pDST remained susceptible. Conclusion: About one in ten people with RR/MDR-TB had bedaquiline-resistance, with half due to primary transmission. One in five people with RR/MDR-TB did not have bedaquiline DST done, highlighting care cascade gaps. Despite long treatment and sustained culture positivity, minimal linezolid resistance occurred.
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