Evidence map›Paper›PMID 38061419›Full record

ArticleInternational journal of antimicrobial agents2024

Linezolid does not improve bactericidal activity of rifampin-containing first-line regimens in animal models of TB meningitis.

Elizabeth W Tucker, Camilo A Ruiz-Bedoya, Filipa Mota, Clara Erice, John Kim, Patricia de Jesus, Ravindra Jahdav, Melissa Bahr, Kelly Flavahan, Xueyi Chen and 3 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of antimicrobial agents, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. Chronic meningitis: diagnostic and therapeutic challenges.Current opinion in infectious diseases · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Observational
  11. 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

13 authors at 3 institutions in 1 country.

Elizabeth W TuckerCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Camilo A Ruiz-BedoyaCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Filipa MotaCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clara EriceCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
John KimCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Patricia de JesusCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ravindra JahdavDepartment of Pharmacology, Physiology and Neuroscience, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
Melissa BahrCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kelly FlavahanCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xueyi ChenCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Charles A PeloquinInfectious Disease Pharmacokinetics Laboratory, Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.
Joel S FreundlichDepartment of Pharmacology, Physiology and Neuroscience, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
Sanjay K JainCenter for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: sjain5@jhmi.edu.
Johns Hopkins University · USRutgers, The State University of New Jersey · USUniversity of Florida · US

Funding

Preclinical modeling to study Tuberculous MeningitisR01AI145435 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$4.0M
Measuring Intralesional Drug Exposures in Cavitary TB using Noninvasive In Vivo PET ImagingR01AI153349 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$3.8M
Novel Imaging and host-directed therapy in pediatric CNS TBK08AI139371 · NIAID · JOHNS HOPKINS UNIVERSITY · PI TUCKER, ELIZABETH WINANS · 2019 to 2023
$994k
NIAID NIH HHS K08 AI139371NIAID NIH HHS R01 AI145435NIAID NIH HHS R01 AI153349
6 · The paper itself

Abstract

Tuberculous meningitis (TB meningitis) is the most devastating form of tuberculosis (TB) and there is a critical need to optimize treatment. Linezolid is approved for multidrug resistant TB and has shown encouraging results in retrospective TB meningitis studies, with several clinical trials underway assessing its additive effects on high-dose (35 mg/kg/day) or standard-dose (10 mg/kg/day) rifampin-containing regimens. However, the efficacy of adjunctive linezolid to rifampin-containing first-line TB meningitis regimens and the tissue pharmacokinetics (PK) in the central nervous system (CNS) are not known. We therefore conducted cross-species studies in two mammalian (rabbits and mice) models of TB meningitis to test the efficacy of linezolid when added to the first-line TB regimen and measure detailed tissue PK (multicompartmental positron emission tomography [PET] imaging and mass spectrometry). Addition of linezolid did not improve the bactericidal activity of the high-dose rifampin-containing regimen in either animal model. Moreover, the addition of linezolid to standard-dose rifampin in mice also did not improve its efficacy. Linezolid penetration (tissue/plasma) into the CNS was compartmentalized with lower than previously reported brain and cerebrospinal fluid (CSF) penetration, which decreased further two weeks after initiation of treatment. These results provide important data regarding the addition of linezolid for the treatment of TB meningitis.

Indexed as

Tuberculosis, MeningealTuberculosis, Multidrug-ResistantAnimalsAntitubercular AgentsLinezolidMammalsMiceModels, AnimalRabbitsRetrospective StudiesRifampinAntitubercular AgentsLinezolidRifampinAntimicrobial regimensLinezolidPositron emission tomographyTuberculous meningitis

Identifiers

PMID38061419
PMCPMC10841818
OpenAlexW4389347697

What OpenQuestion holds

Textmetadata
LicenceTDM
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.