Evidence map›Paper›PMID 26870788›Full record

Trial reportEBioMedicine2015

Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

Taeksun Song, Myungsun Lee, Han-Seung Jeon, Yumi Park, Lori E Dodd, Véronique Dartois, Dean Follman, Jing Wang, Ying Cai, Lisa C Goldfeder and 6 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06590428 (Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis), which is not on this map. Cited by 84 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 4 pooled it
5.6field-weighted citation impact, top 3% 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.

NCT06590428 narecruitingnot on this mapstarted 2026, after this paper: background citation

Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis

TypeinterventionalSponsorAlbert Einstein College of MedicineRan2026 to 2029Enrolled280ConditionsRifampin-resistant Tuberculosis, Drug-resistant TuberculosisArmsTherapeutic Drug Monitoring for Linezolid
3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 135 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019
    Guideline
  4. Pooled it
  5. Trial
  6. Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
  7. Trial
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 3 countries.

Taeksun SongInternational Tuberculosis Research Center, Changwon, Republic of Korea.
Myungsun LeeInternational Tuberculosis Research Center, Changwon, Republic of Korea.
Han-Seung JeonInternational Tuberculosis Research Center, Changwon, Republic of Korea.
Yumi ParkInternational Tuberculosis Research Center, Changwon, Republic of Korea.
Lori E DoddBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Véronique DartoisPublic Health Research Institute, New Jersey Medical School, Rutgers, Newark, NJ, USA.
Dean FollmanBiostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jing WangClinical Research Directorate, Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Ying CaiTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lisa C GoldfederTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kenneth N OlivierCardiovascular and Pulmonary Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Yingda XieTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Laura E ViaTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, 7701, Republic of South Africa.
Sang Nae ChoDepartment of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.
Clifton E BarryTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, 7701, Republic of South Africa.
Ray Y ChenTuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USInternational Tuberculosis Research Center · KRLeidos (United States) · USRutgers, The State University of New Jersey · USYonsei University · KR

Funding

Bronchiectasis and chronic airway infectionZIAHL006200 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FENNELLY, KEVIN · 2015 to 2025
$25.1M
International Research in Korea: Clinical Studies of Drug-Resistant TuberculosisZIAAI001067 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2017
$6.9M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P < 0·0001). Increasing mean linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

Indexed as

AdultAntitubercular AgentsComorbidityDrug MonitoringExtensively Drug-Resistant TuberculosisFemaleGenes, MitochondrialGenes, rRNAHumansLinezolidMaleMiddle AgedMitochondriaPolymorphism, Single NucleotideRisk FactorsAntitubercular AgentsLinezolidAdverse eventsDrug resistantLinezolidMitochondrial toxicityTherapeutic drug monitoringTuberculosis

Identifiers

PMID26870788
PMCPMC4740314
OpenAlexW1960472620

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.