Evidence map›Paper›PMID 38376228›Full record

ArticleAntimicrobial agents and chemotherapy2024

Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis.

Si-Yang Li, Sandeep Tyagi, Heena Soni, Fabrice Betoudji, Paul J Converse, Khisimuzi Mdluli, Anna M Upton, Nader Fotouhi, David Barros-Aguirre, Lluís Ballell and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Antimicrobial agents and chemotherapy · 2026
    Article
  3. Review
  4. Frontiers in microbiology · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. The impact ofFrontiers in immunology · 2024
    Review
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

12 authors at 3 institutions in 2 countries.

Si-Yang Li *Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sandeep Tyagi *Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Heena Soni *Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Fabrice BetoudjiCenter for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Paul J ConverseCenter for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Khisimuzi MdluliTB Alliance: Global Alliance for Tuberculosis Drug Development, New York, New York, USA.
Anna M UptonTB Alliance: Global Alliance for Tuberculosis Drug Development, New York, New York, USA.
Nader FotouhiTB Alliance: Global Alliance for Tuberculosis Drug Development, New York, New York, USA.
David Barros-AguirreGlobal Health Medicines R&D, GlaxoSmithKline R&D Limited, Tres Cantos, Madrid, Spain.ORCID 0000-0002-4099-0438
Lluís BallellGlobal Health Medicines R&D, GlaxoSmithKline R&D Limited, Tres Cantos, Madrid, Spain.
Elena Jimenez-NavarroGlobal Health Medicines R&D, GlaxoSmithKline R&D Limited, Tres Cantos, Madrid, Spain.
Eric L NuermbergerCenter for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0003-1440-9889
Johns Hopkins University · USGlaxoSmithKline (Spain) · ESTB Alliance · US

Funding

Bill and Melinda Gates Foundation (GF) OPP1178195European Union 7th Framework Program FP-2007-2013Orchid Grant Agreement 261378Tres Cantos Open Lab Foundation TC049
6 · The paper itself

Abstract

The combination of bedaquiline, pretomanid, and linezolid (BPaL) has become a preferred regimen for treating multidrug- and extensively drug-resistant tuberculosis (TB). However, treatment-limiting toxicities of linezolid and reports of emerging bedaquiline and pretomanid resistance necessitate efforts to develop new short-course oral regimens. We recently found that the addition of GSK2556286 increases the bactericidal and sterilizing activity of BPa-containing regimens in a well-established BALB/c mouse model of tuberculosis. Here, we used this model to evaluate the potential of new regimens combining bedaquiline or the more potent diarylquinoline TBAJ-587 with GSK2556286 and the DprE1 inhibitor TBA-7371, all of which are currently in early-phase clinical trials. We found the combination of bedaquiline, GSK2556286, and TBA-7371 to be more active than the first-line regimen and nearly as effective as BPaL in terms of bactericidal and sterilizing activity. In addition, we found that GSK2556286 and TBA-7371 were as effective as pretomanid and the novel oxazolidinone TBI-223 when either drug pair was combined with TBAJ-587 and that the addition of GSK2556286 increased the bactericidal activity of the TBAJ-587, pretomanid, and TBI-223 combination. We conclude that GSK2556286 and TBA-7371 have the potential to replace pretomanid, an oxazolidinone, or both components, in combination with bedaquiline or TBAJ-587.

Indexed as

Mycobacterium tuberculosisNitroimidazolesOxazolidinonesTuberculosisTuberculosis, Multidrug-ResistantAnimalsAntitubercular AgentsDiarylquinolinesLinezolidMiceAntitubercular AgentsbedaquilineDiarylquinolinesLinezolidNitroimidazolesOxazolidinonespretomanidbedaquilineGSK2556286linezolidmouse modelMycobacterium tuberculosispretomanidTBA-7371TBAJ-587TBI-223tuberculosis

Identifiers

PMID38376228
PMCPMC10989019
OpenAlexW4391955454

What OpenQuestion holds

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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.