title: Rapid-onset, linezolid-induced lactic acidosis in MELAS.
abstract: Due to their prokaryotic origins, mitochondria are susceptible to a number of antibiotics that target the bacterial ribosome, and this vulnerability is exacerbated by certain mutations of the mitochondrial genome. MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome is characterised by biochemical and structural abnormalities of the muscle mitochondria, in which episodes of lactic acidosis stem from dysfunction of assembled respiratory complex I. Linezolid is an oxazolidinone antibiotic that has been reported to induce lactic acidosis, especially after prolonged administration, through inhibition of the mitochondrially synthesised components of oxidative phosphorylation. We report a patient with longstanding MELAS who suffered a severe lactic acidosis of rapid onset, with associated features of mitochondrial failure, shortly after the commencement of linezolid therapy and in the context of an otherwise improving clinical picture. This case emphasises the importance of circumspection when utilising drugs known to be toxic to the mitochondrion in patients with mitochondrial disease. In particular, given the biochemically plausible interaction, it would seem prudent to avoid the use of linezolid in patients with MELAS whenever possible.
authors: Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. thomascope@gmail.com
authors: Thomas E
authors: TE
authors: Cope
authors: Robert
authors: R
authors: McFarland
authors: Andrew
authors: A
authors: Schaefer
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects*; D000140:Acidosis, Lactic / Q000139:chemically induced*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D000069349:Linezolid; D017241:MELAS Syndrome / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid