Adding Intranasal to Oral Administration of an Ultra-Rapid Near-Universal Drug Regimen Accelerates Relapse-Free Cure of Tuberculosis in Mice.

Bai-Yu Lee, Daniel L Clemens, Saša Masleša-Galic, Susana Nava, Chiao-Yueh Lo, Jeffrey I Zink, Marcus A Horwitz

Abstract read

In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Bai-Yu LeeDivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0003-1730-1486

Daniel L ClemensDivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0003-0421-7306

Saša Masleša-GalicDivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

Susana NavaDivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

Chiao-Yueh LoDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-6572-0194

Jeffrey I ZinkDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-9792-4976

Marcus A HorwitzDivision of Infectious Diseases, Department of Medicine, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0001-6525-7147

Funding

Department of Defense CDMRP PR190949

6 · The paper itself

Abstract

We previously identified a potent 4-drug oral regimen comprising clofazimine, bedaquiline, pyrazinamide, and delamanid (parabolic response surface [PRS] regimen V) that dramatically shortens by approximately 85% the treatment duration needed to attain relapse-free cure of tuberculosis in mice compared with the standard regimen. Here, we investigated if intranasal administration of the PRS regimen V antibiotics bedaquiline and delamanid on top of the oral regimen would further accelerate tuberculosis cure in mice. We show that adding the intranasal to oral regimen further lowers lung burden of tubercle bacilli and significantly more rapidly achieves relapse-free cure. Hence, adding inhalational to oral therapy can potentially accelerate cure of tuberculosis.

Indexed as

Antitubercular AgentsTuberculosisAdministration, IntranasalAdministration, OralAnimalsClofazimineDiarylquinolinesDisease Models, AnimalDrug Therapy, CombinationFemaleLungMiceMycobacterium tuberculosisNitroimidazolesOxazolesPyrazinamideAntitubercular AgentsbedaquilineClofazimineDiarylquinolinesNitroimidazolesOPC-67683OxazolesPyrazinamidebedaquilinedelamanidintranasal therapyrelapse-free curetuberculosis

Identifiers

PMID40498595

DOI10.1093/infdis/jiaf315

PMCPMC12455299

What OpenQuestion holds

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LicenceCC BY

Read underepoch 390

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.