Linezolid is an antibiotic belonging to the oxazolidinone class, used to treat serious bacterial infections, including those caused by Gram-positive bacteria resistant to other antibiotics. Below is a comprehensive overview of the pharmacology of linezolid:
Mechanism of Action
Linezolid works by inhibiting bacterial protein synthesis. It binds to the 23S ribosomal RNA of the 50S subunit, preventing the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. This action is unique to oxazolidinones, making linezolid effective against bacteria resistant to other antibiotics.
Pharmacokinetics
- Absorption: Linezolid is rapidly and completely absorbed after oral administration, with bioavailability close to 100%. This allows for oral and intravenous administration to be interchangeable.
- Distribution: It is widely distributed throughout the body, including in skin, lung, and other tissues.
- Metabolism: Linezolid is metabolized in the liver, with the formation of two inactive metabolites.
- Excretion: It is excreted primarily in the urine, both as unchanged drug and metabolites.
Adverse Effects
- Myelosuppression: Including thrombocytopenia, anemia, and leukopenia, particularly with prolonged use.
- Peripheral and Optic Neuropathy: With long-term use.
- Gastrointestinal Disturbances: Such as nausea, vomiting, and diarrhea.
- Headache and Insomnia
- Lactic Acidosis: Rare, but serious.
Clinical Uses
- Pneumonia: Including hospital-acquired and ventilator-associated pneumonia.
- Skin and Soft Tissue Infections: Including diabetic foot infections.
- Vancomycin-Resistant Enterococcus faecium Infections
- Methicillin-Resistant Staphylococcus aureus (MRSA) Infections
- Complicated and Uncomplicated Skin and Skin Structure Infections
Resistance
Resistance to linezolid can develop through mutations in the 23S rRNA or through the acquisition of cfr gene, which encodes a methyltransferase that modifies the ribosome.
Drug Interactions
- Serotonergic Drugs: Linezolid is a weak inhibitor of monoamine oxidase, and its use with other serotonergic drugs can lead to serotonin syndrome.
- Tyramine-Rich Foods: Linezolid’s monoamine oxidase inhibition can lead to hypertensive crisis when consumed with foods high in tyramine.
- Sympathomimetic Drugs: Such as pseudoephedrine, can lead to increased blood pressure when used with linezolid.
Contraindications
- Hypersensitivity: To linezolid or any component of the formulation.
- Uncontrolled Hypertension: Due to the risk of hypertensive crisis.
- Pheochromocytoma: Due to the risk of hypertensive crisis.
- Concomitant Use with Serotonergic Agents: Due to the risk of serotonin syndrome.
Monitoring
Patients on linezolid, especially those on prolonged therapy, should be monitored for signs of myelosuppression, neuropathy, and lactic acidosis. Regular blood counts and monitoring of visual and neurological function are recommended.
Conclusion
Linezolid is a valuable antibiotic for the treatment of serious infections caused by Gram-positive bacteria, including strains resistant to other antibiotics. Its unique mechanism of action makes it a crucial option in the fight against antibiotic-resistant bacteria. However, its use is associated with significant risks, and careful monitoring is required to minimize the risk of adverse effects. Appropriate use, considering the potential risks and benefits, is essential to ensure safe and effective treatment.
