A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.
Pathog Immun
; 9(2): 25-42, 2024.
Article
em En
| MEDLINE
| ID: mdl-38939039
ABSTRACT
Background:
Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.Objective:
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:
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:
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 (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval 0.42 - 0.84).Conclusions:
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 SBSN biomarker in more diverse populations are warranted.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Pathog Immun
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha