Evidence map›Paper›PMID 41724179›Full record

ArticleThe Lancet. Microbe2026

Bedaquiline resistance in patients with Xpert MTB/RIF Ultra-tested rifampicin-resistant tuberculosis in the Western Cape, South Africa: a prospective study.

Janré Steyn, Jennifer Williams, Fahd Naufal, Jason Limberis, Melanie Grobbelaar, Nabila Ismail, Yonas Ghebrekristos, Christoffel J Opperman, Alina Nalyvayko, Sarishna Singh and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Microbe, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Janré SteynSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Jennifer WilliamsSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Fahd NaufalDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California San Francisco, San Francisco, CA, USA.
Jason LimberisDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California San Francisco, San Francisco, CA, USA.
Melanie GrobbelaarSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Nabila IsmailSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Yonas GhebrekristosSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Greenpoint TB-Laboratory, Cape Town, South Africa.
Christoffel J OppermanSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Greenpoint TB-Laboratory, Cape Town, South Africa; Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Alina NalyvaykoDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California San Francisco, San Francisco, CA, USA.
Sarishna SinghSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Greenpoint TB-Laboratory, Cape Town, South Africa.
Rebecca E ColmanDivision of Pulmonary, Critical Care, Sleep Medicine, and Physiology, University of California San Diego, San Diego, CA, USA.
Timothy C RodwellDivision of Pulmonary, Critical Care, Sleep Medicine, and Physiology, University of California San Diego, San Diego, CA, USA.
Grant TheronSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; National Health Laboratory Service, Greenpoint TB-Laboratory, Cape Town, South Africa.
Robin M WarrenSAMRC Centre for Tuberculosis Research, DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
John Z MetcalfeDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California San Francisco, San Francisco, CA, USA. Electronic address: john.metcalfe@ucsf.edu.

Funding

Handheld and population-based sequencing for rapid detection of new and repurposed drug resistance in M. tuberculosisR01AI153213 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI David M Engelthaler, John Zapata Metcalfe · 2021 to 2026
$3.7M
NIAID NIH HHS R01 AI153213
6 · The paper itself

Abstract

backgroundBedaquiline-containing regimens have been widely used to treat patients with drug-resistant tuberculosis in South Africa since 2019. We aimed to estimate the prevalence of bedaquiline resistance among patients in the Western Cape with rifampicin-resistant tuberculosis tested by Xpert MTB/RIF Ultra (Xpert).

methodsThis prospective study analysed consecutive Mycobacterium tuberculosis diagnostic isolates collected from patients with Xpert-tested rifampicin-resistant tuberculosis in the Western Cape, South Africa, between March 30, 2023, and Jan 3, 2024. We used the Deeplex Myc-TB assay within routine clinical workflows to test genotypic resistance to bedaquiline and other antituberculosis drugs; mmpR5 variants were classified according to Deeplex version 3.0.1 extended catalogue. Phenotypic drug susceptibility information was derived from the National Health Laboratory System and Stellenbosch University for isolates with a Deeplex-identified mmpR5 variant. We estimated the prevalence of bedaquiline resistance and the diagnostic accuracy of Deeplex for bedaquiline susceptibility using a composite genotypic-phenotypic reference standard.

findingsOf 701 sputum sediments, 131 (19%) were culture-negative. Of the 570 isolates accumulated during the study period, Deeplex was not performed for 139 during intervals trialling workflow optimisation procedures. Of 431 isolates, we successfully sequenced 401 (93%), of which 15 (4%) were found to be rifampicin-susceptible; 364 (91%) analysed isolates were baseline and 37 (9%) were longitudinal (median estimated time since previous diagnosis of 5·4 months [IQR 3·7-8·0]). Bedaquiline resistance was detected in 45 (12% [95% CI 9-16]) of 364 baseline and 15 (41% [25-58]) of 37 longitudinal isolates. Deeplex-tested resistance-associated and uncharacterised mmpR5 variants had a similar likelihood of being phenotypic drug susceptibility testing-resistant (37 [97%] of 38 and 16 [94%] of 17, respectively; p=0·53). Combining both types of variants, Deeplex had a sensitivity of 93% (95% CI 83-98) and specificity of 99% (97-100).

interpretationIn a prospective, representative sample of patients with Xpert-tested rifampicin-resistant tuberculosis, we found an elevated prevalence of bedaquiline resistance, particularly in patients with recent tuberculosis treatment. Efficient and accurate surveillance for bedaquiline resistance should be a high programmatic priority.

fundingThe National Institute of Allergy and Infectious Diseases (at the National Institutes of Health) and Unitaid.

Indexed as

Antitubercular AgentsDiarylquinolinesMycobacterium tuberculosisRifampinTuberculosis, Multidrug-ResistantDrug Resistance, BacterialFemaleGenotypeHumansMaleMicrobial Sensitivity TestsPrevalenceProspective StudiesSouth AfricaAntitubercular AgentsbedaquilineDiarylquinolinesRifampin

Identifiers

PMID41724179
PMCPMC13100955

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.