Linezolid Associated Neuropathy in M/XDR‑TB: Pathophysiological Insights and Emerging Therapeutic Horizons—A Case Series Analysis

Abstract

Linezolid (LZD) remains a cornerstone drug in the management of drug-resistant tuberculosis (TB), but its prolonged use is limited by dose-dependent mitochondrial toxicity, particularly peripheral neuropathy and hematological suppression. We present a case series of five drug-resistant TB patients, three females and two males aged 19–45 years, all human immunodeficiency virus-negative and without major comorbidities treated with an LZD-containing all-oral longer regimen. All five developed peripheral neuropathy attributable to LZD, with additional toxicities of severe anemia in one patient and ocular neuropathy in another. The median time to onset of neuropathy was 3.7 months, ranging from 1 to nearly 5 months. LZD was discontinued in all cases due to toxicity and replaced with delamanid, and no mortality was observed during the follow-up. This series underscores the universal occurrence of LZD-induced neuropathy in a small cohort, independent of the resistance pattern, with risk linked more to cumulative exposure and duration than baseline resistance. Careful monitoring beyond the third month of therapy is essential to prevent irreversible complications, and strategies such as dose adjustment, intermittent administration, or therapeutic drug monitoring may help preserve LZD’s utility. Early recognition of neuropathy turns silence into safety, ensuring cure with compassion.