Evidence map›Paper›PMID 40543523›Full record

Observational studyThe Lancet. Infectious diseases2025

Treatment outcomes of bedaquiline-resistant tuberculosis: a retrospective and matched cohort study.

Lindokuhle Mdlenyani, Zahraa Mohamed, Jacob A M Stadler, Nomfuneko Mtwa, Graeme Meintjes, Robin Warren, Matthew J Saunders, Johanna Kuhlin, Sean Wasserman

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. When are Uncontrolled Trials in TB Scientifically and Ethically Justified: Borrowing Wisdom From Early AIDS Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  3. Article
  4. We Are Underprepared for Bedaquiline Resistance: A Call for Clinical and Programmatic Readiness.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Menaquinone depletion resensitises bedaquiline-resistant tuberculosis.bioRxiv : the preprint server for biology · 2026
    Article
  12. Review
  13. Article
  14. Article
  15. New drugs for the management of tuberculosis.Current opinion in infectious diseases · 2025
    Review
  16. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Lindokuhle MdlenyaniDepartment of Health, Eastern Cape Province, East London, South Africa.
Zahraa MohamedWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jacob A M StadlerWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
Nomfuneko MtwaDepartment of Health, Eastern Cape Province, East London, South Africa.
Graeme MeintjesWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa; Blizard Institute, Queen Mary University of London, London, UK.
Robin WarrenDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Matthew J SaundersInstitute for Infection and Immunity, City St George's, University of London, London, UK.
Johanna KuhlinWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Sean WassermanWellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa; Institute for Infection and Immunity, City St George's, University of London, London, UK. Electronic address: swasserm@sgul.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRising prevalence of bedaquiline resistance undermines benefits from this life-saving drug for rifampicin-resistant tuberculosis (RR tuberculosis). Despite increasing awareness, patient-level outcomes for bedaquiline-resistant tuberculosis have not been well characterised and case management has been poorly defined.

methodsWe did a retrospective cohort study of bedaquiline-resistant tuberculosis with matched RR tuberculosis controls at a tuberculosis referral hospital in East London, South Africa. Cases included patients aged 13 years or older with a phenotypic bedaquiline-resistant Mycobacterium tuberculosis isolate identified between Jan 1, 2018 and June 30, 2023. Controls with confirmed bedaquiline-susceptible tuberculosis, matched 1:1 by baseline culture status, age, and HIV status, were selected from a prospective observational study conducted during an overlapping period at the same facility. Primary outcomes included time to sputum culture conversion (SCC), a modified WHO-defined unfavourable outcome, and tuberculosis-free survival (alive, with SCC, and in care or treatment completed) up until 18 months. Adjusted analyses used Cox proportional hazards and logistic regression models.

findings82 patients with bedaquiline-resistant tuberculosis were included, 57 (70%) of whom were HIV positive. Bedaquiline was prescribed for 72 (88%) of 82 patients and meropenem (plus amoxicillin-clavulanate) for 32 (39%) of 82. Together with bedaquiline, the most frequently prescribed drugs included clofazimine, linezolid, and terizidone. Median time to SCC after treatment initiation was 175 days (IQR 100-254) in the bedaquiline-resistant cohort and 32 days (30-42) in matched controls. In the analysis of the combined cohorts, bedaquiline resistance (adjusted hazard ratio 0·03, 95% CI 0·0023-0·29, p=0·003) was associated with longer time to SCC when adjusted for baseline microscopy grade and baseline fluoroquinolone resistance. WHO treatment outcomes in those with bedaquiline-resistant tuberculosis were unfavourable in 54 (67%) of 81 patients, driven by treatment failure in 35 (43%) of 81. At 18 months, 43 (52%) of 82 patients had reached tuberculosis-free survival, 19 (23%) of 82 had died, and 50 (79%) of 63 survivors were still on treatment.

interpretationCurrent treatment options for bedaquiline-resistant tuberculosis result in prolonged therapy, delayed microbiological responses, and poor clinical outcomes. Implementation of more rapid resistance testing, including targeted next-generation sequencing, and access to novel treatment options within randomised controlled trials for bedaquiline-resistant tuberculosis, are priorities for tuberculosis programmes.

fundingThe South African Medical Research Council.

Indexed as

Antitubercular AgentsDiarylquinolinesMycobacterium tuberculosisTuberculosis, Multidrug-ResistantAdultCase-Control StudiesFemaleHumansMaleMiddle AgedRetrospective StudiesSouth AfricaSputumTreatment OutcomeYoung AdultAntitubercular AgentsbedaquilineDiarylquinolines

Identifiers

PMID40543523
PMCPMC12662777

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.