Linezolid is a member of the oxazolidinones, a new class ofsynthetic antimicrobials. It is active against gram-positive organisms including staphylococci, streptococci, enterococci, gram-positive anaerobic cocci, and gram-positive rods such as corynebacteria, Nocardia sp, and L monocytogenes. It is primarily a bacteriostaticagent but is bactericidal against streptococci. It is also active against Mycobacterium tuberculosis.
Linezolid inhibits protein synthesis by preventing formation of the ribosome complex that initiates protein synthesis. Its unique binding site, located on 23S ribosomal RNA of the 50S subunit, results in no cross-resistance with other drug classes. Resistance is caused by mutation of the linezolid binding site on 23S ribosomal RNA.
Linezolid is 100% bioavailable after oral administration and has a half-life of 4–6 hours. It is metabolized by oxidative metabolism, yielding two inactive metabolites. It is neither an inducer nor an inhibitor of cytochrome P450 enzymes. Peak serum concentra-tions average 18 mcg/mL following a 600-mg oral dose. The rec-ommended dosage for most indications is 600 mg twice daily, either orally or intravenously.
Linezolid is approved for vancomycin-resistant E faecium infec-tions; nosocomial pneumonia; community-acquired pneumonia; and both complicated and uncomplicated skin and soft tissue infections caused by susceptible gram-positive bacteria. Off-label uses of linezolid include treatment of multidrug-resistant tubercu-losis and Nocardia infections.
The principal toxicity of linezolid is hematologic; the effects are reversible and generally mild. Thrombocytopenia is the most common manifestation (seen in approximately 3% of treatment courses), particularly when the drug is administered for longer than 2 weeks. Anemia and neutropenia may also occur, most commonly in patients with a predisposition to or underlying bone marrow suppression. Cases of optic and peripheral neuropathy and lactic acidosis have been reported with prolonged courses of linezolid. These side effects are thought to be related to linezolid-induced inhibition of mitochondrial protein synthesis. There are case reports of serotonin syndrome occurring when linezolid is co-administered with serotonergic drugs, most frequently selective serotonin reuptake inhibitor antidepressants. The FDA issued a warning regarding the use of the drug with serotonergic agents in 2011.