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Linezolid Lactic Acidosis — SCE Infectious Diseases MCQ

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HardAntimicrobial StewardshipLinezolid Lactic AcidosisSCE Infectious Diseases

A 45-year-old man develops a rare complication of Linezolid therapy: lactic acidosis (pH 7.22, lactate 8.5 mmol/L) after 8 weeks of treatment for MRSA osteomyelitis. What is the mechanism?

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Correct answer: C — Linezolid inhibits human mitochondrial protein synthesis (similar to its bacterial ribosomal action) causing impaired oxidative phosphorylation and lactic acidosis

Linezolid inhibits both bacterial 50S ribosomal subunit AND human mitochondrial ribosomes (which share structural homology). Prolonged use causes mitochondrial dysfunction in human cells: impaired oxidative phosphorylation → lactic acidosis, myelosuppression (thrombocytopenia, anaemia), and peripheral/optic neuropathy. Lactic acidosis is the most serious metabolic complication and can be fatal. Linezolid must be stopped immediately. Lactate should normalise within days of cessation. This limits Linezolid to courses of ideally <28 days when possible.

Reference: BNF 2024 – Linezolid; BSAC 2023 – Linezolid toxicity