Rapid-onset, linezolid-induced lactic acidosis in MELAS

Area of Science:

• Mitochondrial biology
• Pharmacology
• Genetics

Background:

• Mitochondria, with prokaryotic origins, are vulnerable to antibiotics targeting bacterial ribosomes.
• Mutations in the mitochondrial genome can worsen antibiotic susceptibility.
• Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome involves muscle mitochondrial dysfunction and lactic acidosis due to Complex I failure.

Observation:

• Linezolid, an oxazolidinone antibiotic, can induce lactic acidosis by inhibiting mitochondrial oxidative phosphorylation.
• A patient with MELAS experienced rapid-onset, severe lactic acidosis after starting linezolid therapy.
• This occurred despite an otherwise improving clinical condition.

Findings:

• The patient's severe lactic acidosis was directly linked to linezolid administration.
• This adverse event highlights the drug's toxicity to mitochondria, particularly in individuals with MELAS.
• The case demonstrates a biochemically plausible interaction between linezolid and mitochondrial dysfunction.

Implications:

• Clinicians should exercise caution when prescribing drugs known to be toxic to mitochondria to patients with mitochondrial diseases.
• Avoiding linezolid in MELAS patients is recommended due to the high risk of severe lactic acidosis.
• This case underscores the need for careful drug selection and monitoring in patients with complex genetic disorders affecting mitochondria.