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Zielinski, N.* ; Baiceanu, D.* ; Dragomir, A.* ; Heyckendorf, J.* ; Ibraim, E.* ; Köhler, N.* ; Leschczyk, C.* ; Popa, C.* ; Rachow, A. ; Sachsenweger, J.* ; Carballo, P.S.* ; Schaub, D.* ; Zeeb, H.* ; Tulu, B.* ; DiNardo, A.R.* ; Lange, C.* ; Reimann, M.*

A transcriptomic biomarker predicting linezolid-associated neuropathy during treatment of drug-resistant tuberculosis.

Pathog. Immun. 9, 25-42 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Sbsn ; Adverse Events ; Linezolid ; Multidrug Resistance ; Neurotoxicity ; Precision Medicine ; Tuberculosis
ISSN (print) / ISBN 2469-2964
e-ISSN 2469-2964
Journal Pathogens and Immunity
Quellenangaben Volume: 9, Issue: 2, Pages: 25-42 Article Number: , Supplement: ,
Publisher Case Western Reserve University
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Global Health (UGH)