Evidence map›Paper›PMID 34796339›Full record

SynthesisThe Lancet. Microbe2021

Genetic variants and their association with phenotypic resistance to bedaquiline in

Nabila Ismail, Emmanuel Rivière, Jason Limberis, Stella Huo, John Z Metcalfe, Rob M Warren, Annelies Van Rie

Open access · goldAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Microbe, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 6% of its field
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

43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  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. Review
  7. Article
  8. Article
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  12. Verapamil and its metabolite norverapamil inhibit theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Dual Mutations inInternational journal of molecular sciences · 2025
    Article
  14. Article
  15. Chemical genetic interactions elucidate pathways controlling tuberculosis antibiotic efficacy during infection.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Frameshift mutations in theAntimicrobial agents and chemotherapy · 2024
    Article
  18. Widespread loss-of-function mutations implicating preexisting resistance to new or repurposed anti-tuberculosis drugs.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024
    Article
  19. Review
  20. 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

7 authors at 5 institutions in 3 countries.

Nabila IsmailSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
Emmanuel RivièreSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
Jason LimberisSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
Stella HuoSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
John Z MetcalfeSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
Rob M WarrenSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
Annelies Van RieSouth African Medical Research Council Centre for Tuberculosis Research and Department of Science and Innovation - National Research Foundation 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 (N Ismail PhD, Prof R M Warren PhD); Family Medicine and Population Health, Faculty of Medicine, University of Antwerp, Antwerp, Belgium (E Rivière MSc, Prof A Van Rie PhD); Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA (J Limberis PhD); Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Centre, University of California, San Francisco, San Francisco, CA, USA (S Huo MSc, Prof J Z Metcalfe PhD).
University of Antwerp · BEUniversity of California, San Francisco · USNational Research Foundation · ZASan Francisco General Hospital · USStellenbosch University · ZA

Funding

Novel next-generation sequencing assay for monitoring multidrug resistant tuberculosis treatment in the setting of HIV infectionR01AI131939 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ENGELTHALER, DAVID M, METCALFE, JOHN ZAPATA · 2018 to 2023
$3.9M
NIAID NIH HHS R01 AI131939
6 · The paper itself

Abstract

backgroundBedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and surveillance of drug resistance emergence. To facilitate molecular assay development, we aimed to identify genomic markers of bedaquiline resistance.

methodsIn this systematic review and individual isolate analysis, we searched Europe PubMed Central and Scopus for studies published from the inception of each database until Oct 19, 2020, that assessed genotypic and phenotypic bedaquiline resistance in clinical or non-clinical

findingsOf 1367 studies identified, 41 published between 2007 and 2020 were eligible for inclusion. We extracted data on 1708 isolates: 1569 (91·9%) clinical isolates and 139 (8·1%) non-clinical isolates. We identified 237 unique variants in

interpretationAbsence of clear genotypic-phenotypic associations for bedaquiline complicates the development of molecular drug susceptibility tests. A concerted global effort is urgently needed to assess the genotypic and phenotypic drug susceptibility of

fundingResearch Foundation Flanders, South African Medical Research Council, Department of Science and Innovation - National Research Foundation, National Institute of Health Institute of Allergy and Infectious Diseases, and Doris Duke Charitable Foundation.

Indexed as

Mycobacterium tuberculosisTuberculosis, Lymph NodeTuberculosis, Multidrug-ResistantAnimalsAntitubercular AgentsData AnalysisDiarylquinolinesHumansMicrobial Sensitivity TestsAntitubercular AgentsbedaquilineDiarylquinolines

Identifiers

PMID34796339
PMCPMC8597953
OpenAlexW3198161252

What OpenQuestion holds

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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.