Evidence map›Paper›PMID 39110473›Full record

ArticleThe Journal of antimicrobial chemotherapy2024

Investigating the treatment shortening potential of a combination of bedaquiline, delamanid and moxifloxacin with and without sutezolid, in a murine tuberculosis model with confirmed drug exposures.

Kerstin Walter, Lindsey H M Te Brake, Ann-Kathrin Lemm, Michael Hoelscher, Elin M Svensson, Christoph Hölscher, Norbert Heinrich

Abstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Combined use of methyl gallate and N-acyl homoserine lactonase YtnP to inhibit biofilm formation in Burkholderia thailandensis.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026
    Article
  2. 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

7 authors.

Kerstin WalterDivision of Infection Immunology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.ORCID 0009-0000-7883-4433
Lindsey H M Te BrakeDepartment of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Ann-Kathrin LemmDivision of Infection Immunology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Michael HoelscherInstitute of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany.
Elin M SvenssonDepartment of Pharmacy, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Christoph HölscherDivision of Infection Immunology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Norbert HeinrichInstitute of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich, Munich, Germany.ORCID 0000-0001-9252-7106

Funding

German Center for Infection Research TTU 02.710German Ministry for Education and ResearchNederlandse Organisatie voor Wetenschappelijk OnderzoekPanACEA 2Swiss State Secretariat for Education, Research, and Innovation
6 · The paper itself

Abstract

backgroundNew and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB/c) of Mycobacterium tuberculosis (Mtb) infection.

methodsTreatment of mice with B25D0.6M200U200, B25D0.6M200, B25D0.6M200(U2003) or H10R10Z150E100 (isoniazid, rifampicin, pyrazinamide, ethambutol, HRZE), started 3 weeks after Mtb infection. Bactericidal activity was assessed after 1, 2, 3 and 4 months of treatment and relapse rates were assessed 3 months after completing treatment durations of 2, 3 and 4 months.

resultsB25D0.6M200U200 generated human equivalent exposures in uninfected BALB/c mice. After 1 month of treatment, a higher bactericidal activity was observed for the B25D0.6M200U200 and the B25D0.6M200 regimen compared to the standard H10R10Z150E100 regimen. Furthermore, 3 months of therapy with both BDM-based regimens resulted in negative lung cultures, whereas all H10R10Z150E100 treated mice were still culture positive. After 3 months of therapy 7% and 13% of mice relapsed receiving B25D0.6M200U200 and B25D0.6M200, respectively, compared to 40% for H10R10Z150E100 treatment showing an increased sterilizing activity of both BDM-based regimens.

conclusionsBDM-based regimens, with and without sutezolid, have a higher efficacy than the HRZE regimen in the BALB/c model of TB, with some improvement by adding sutezolid. By translating these results to TB patients, this novel BDMU regimen should be able to reduce treatment duration by 25% compared to HRZE therapy.

Indexed as

Antitubercular AgentsDiarylquinolinesDisease Models, AnimalDrug Therapy, CombinationMice, Inbred BALB CMoxifloxacinMycobacterium tuberculosisNitroimidazolesOxazolesAnimalsFemaleIsoxazolesMiceOxazolidinonesPyrazinamideTreatment OutcomeAntitubercular AgentsbedaquilineDiarylquinolinesIsoxazolesMoxifloxacinNitroimidazolesOPC-67683OxazolesOxazolidinonesPyrazinamideterizidone

Identifiers

PMID39110473
PMCPMC11441997

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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.