Evidence map›Paper›PMID 40029856›Full record

ArticlePloS one2025

Pharmacometabolomics in TB meningitis-Understanding the pharmacokinetic, metabolic, and immune factors associated with anti-TB drug concentrations in cerebrospinal fluid.

Jeffrey M Collins, Maia Kipiani, Yutong Jin, Ashish A Sharma, Jeffrey A Tomalka, Teona Avaliani, Mariam Gujabidze, Tinatin Bakuradze, Shorena Sabanadze, Zaza Avaliani and 5 more

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Jeffrey M CollinsDepartment of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.ORCID https://orcid.org/0000-0002-6574-0873
Maia KipianiNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Yutong JinDepartment of Biostatistics, Rollins School of Public Health of Emory University, Atlanta, Georgia, United States of America.ORCID https://orcid.org/0000-0002-8996-4812
Ashish A SharmaDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Jeffrey A TomalkaDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Teona AvalianiNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Mariam GujabidzeNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Tinatin BakuradzeNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Shorena SabanadzeNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Zaza AvalianiNational Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.
Henry M BlumbergDepartment of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
David BenkeserDepartment of Biostatistics, Rollins School of Public Health of Emory University, Atlanta, Georgia, United States of America.
Dean P JonesDepartment of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Charles PeloquinDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.ORCID https://orcid.org/0000-0001-9002-7052
Russell R KempkerDepartment of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.ORCID https://orcid.org/0000-0002-7188-4996

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
Emory/Georgia TB Research Advancement Center (TRAC)P30AI168386 · NIAID · EMORY UNIVERSITY · PI Neel Rajnikant Gandhi, Jyothi Rengarajan · 2022 to 2026
$5.8M
Emory-Georgia TB Research Training ProgramD43TW007124 · FIC · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Nestani Tukvadze · 2004 to 2026
$4.6M
High resolution plasma metabolomics to identify biomarkers of tuberculosisK23AI144040 · NIAID · EMORY UNIVERSITY · PI COLLINS, JEFFREY M · 2019 to 2023
$911k
Intra Cavitary Pharmacokinetics and Drug Resistance in Pulmonary TuberculosisK23AI103044 · NIAID · EMORY UNIVERSITY · PI KEMPKER, RUSSELL RYAN · 2013 to 2017
$910k
An Exploratory Study of Anti-Tuberculosis Drug Penetration into Cerebrospinal FluidR03AI139871 · NIAID · EMORY UNIVERSITY · PI KEMPKER, RUSSELL RYAN · 2018 to 2019
$168k
FIC NIH HHS D43 TW007124NCATS NIH HHS UL1 TR002378NIAID NIH HHS K23 AI103044NIAID NIH HHS K23 AI144040NIAID NIH HHS P30 AI050409NIAID NIH HHS P30 AI168386NIAID NIH HHS R03 AI139871
6 · The paper itself

Abstract

Poor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver of morbidity and mortality in TB meningitis (TBM). While the amount of a particular drug that crosses into the cerebrospinal fluid (CSF) varies from person to person, little is known about the host factors associated with interindividual differences in CSF concentrations of anti-TB drugs. In patients diagnosed with TBM from the country of Georgia (n = 17), we investigate the association between CSF concentrations of anti-TB antibiotics and multiple host factors including serum drug concentrations and CSF concentrations of metabolites and cytokines. We found > 2-fold differences in CSF concentrations of anti-TB antibiotics from person to person for all drugs tested including cycloserine, ethambutol, imipenem, isoniazid, levofloxacin, linezolid, moxifloxacin, pyrazinamide, and rifampin. While serum drug concentrations explained over 30% of the variation in CSF drug concentrations for cycloserine, isoniazid, linezolid, and pyrazinamide (adjusted R2 ≥ 0.3, p < 0.001 for all), there was no significant association between serum concentrations of imipenem and ethambutol and their respective CSF concentrations. CSF concentrations of carnitines were significantly associated with concentrations of ethambutol and imipenem (q < 0.05), and imipenem was the only antibiotic significantly associated with CSF cytokine concentrations. These results indicate that there is high interindividual variability in CSF drug concentrations in patients treated for TBM, which is only partially explained by differences in serum drug concentrations. With the exception of imipenem, there was no association between CSF drug concentrations and concentrations of cytokines and chemokines.

Indexed as

Antitubercular AgentsMetabolomicsTuberculosis, MeningealAdultAgedCycloserineCytokinesEthambutolFemaleHumansIsoniazidMaleMiddle AgedYoung AdultAntitubercular AgentsCycloserineCytokinesEthambutolIsoniazid

Identifiers

PMID40029856
PMCPMC11875335

What Socratic holds

Textmetadata
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 Socratic graph.