A patient on a longer individualised MDR-TB regimen has received linezolid 600 mg daily for 7 months and reports numbness of the feet. Full blood count shows haemoglobin 8.9 g/dL with macrocytosis. The mechanism of action of linezolid and the toxicity demonstrated here are best described as:

• A Inhibition of DNA gyrase; nephrotoxicity and hypokalaemia
• B Inhibition of ATP synthase; lactic acidosis and pancreatitis
• C Inhibition of mycolic acid synthesis; hepatotoxicity and hyperuricaemia
• D Inhibition of the 50S ribosomal subunit at the 23S rRNA site; mitochondrial toxicity causing myelosuppression and neuropathy ✓

Explanation

Linezolid binds the 23S rRNA of the 50S ribosomal subunit and prevents formation of the initiation complex, blocking protein synthesis. Because mitochondrial ribosomes resemble bacterial ribosomes, prolonged therapy causes mitochondrial toxicity: anaemia, thrombocytopenia, lactic acidosis, and peripheral and optic neuropathy. Duration beyond 28 days sharply raises risk, so WHO recommends reducing to 300 mg or stopping if toxicity appears. DNA gyrase inhibition describes fluoroquinolones.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.