A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.
SBSN
adverse events
linezolid
multidrug resistance
neurotoxicity
precision medicine
tuberculosis
Journal
Pathogens & immunity
ISSN: 2469-2964
Titre abrégé: Pathog Immun
Pays: United States
ID NLM: 101683909
Informations de publication
Date de publication:
2024
2024
Historique:
received:
01
04
2024
accepted:
28
05
2024
medline:
28
6
2024
pubmed:
28
6
2024
entrez:
28
6
2024
Statut:
epublish
Résumé
Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin ( We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the
Sections du résumé
Background
UNASSIGNED
Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.
Objective
UNASSIGNED
We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy.
Methods
UNASSIGNED
Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania.
Results
UNASSIGNED
A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (
Conclusions
UNASSIGNED
We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the
Identifiants
pubmed: 38939039
doi: 10.20411/pai.v9i2.705
pii: pai.v9i2.705
pmc: PMC11210591
doi:
Types de publication
Journal Article
Langues
eng
Pagination
25-42Informations de copyright
Copyright © 2024 Pathogens and Immunity.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to declare.