Academic Journal
Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis
| Title: | Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis |
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| Authors: | Taeksun Song, Myungsun Lee, Han-Seung Jeon, Yumi Park, Lori E. Dodd, Véronique Dartois, Dean Follman, Jing Wang, Ying Cai, Lisa C. Goldfeder, Kenneth N. Olivier, Yingda Xie, Laura E. Via, Sang Nae Cho, Clifton E. Barry III, Ray Y. Chen |
| Source: | EBioMedicine, Vol 2, Iss 11, Pp 1627-1633 (2015) |
| Publisher Information: | Elsevier, 2015. |
| Publication Year: | 2015 |
| Collection: | LCC:Medicine LCC:Medicine (General) |
| Subject Terms: | Mitochondrial toxicity, Adverse events, Linezolid, Tuberculosis, Drug resistant, Therapeutic drug monitoring, Medicine, Medicine (General), R5-920 |
| More Details: | 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 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352396415301663; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2015.09.051 |
| Access URL: | https://doaj.org/article/7beaa75555b04827aa0e2b13b0e0cec4 |
| Accession Number: | edsdoj.7beaa75555b04827aa0e2b13b0e0cec4 |
| Database: | Directory of Open Access Journals |
| ISSN: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2015.09.051 |
| Published in: | EBioMedicine |
| Language: | English |