Linezolid exerts its antibacterial effect by inhibiting bacterial protein synthesis. It binds to the 23S ribosomal RNA of the 50S subunit, preventing the formation of the 70S initiation complex. This action blocks the translation process, leading to bacteriostatic effects (inhibition of bacterial growth) against most susceptible organisms. However, it may exhibit bactericidal activity (killing of bacteria) against some strains of Streptococcus pneumoniae.

Linezolid is effective against a wide range of Gram-positive bacteria, including:

• Methicillin-resistant Staphylococcus aureus (MRSA)
• Vancomycin-resistant enterococci (VRE)
• Penicillin-resistant Streptococcus pneumoniae
• Coagulase-negative staphylococci
• Anaerobic bacteria (e.g., Clostridium species)

It is not effective against most Gram-negative bacteria due to their intrinsic resistance mechanisms.

Linezolid is primarily used to treat infections caused by multidrug-resistant Gram-positive bacteria. Its clinical applications include:

1. Skin and Soft Tissue Infections:
   • Complicated skin and soft tissue infections (cSSTIs) caused by MRSA or other susceptible organisms.
2. Pneumonia:
   • Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae (including multidrug-resistant strains).
   • Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), caused by MRSA.
3. Bacteremia and Sepsis:
   • Infections caused by MRSA or VRE.
4. Vancomycin-Resistant Enterococci (VRE) Infections:
   • Urinary tract infections (UTIs), endocarditis, and other systemic infections.
5. Off-Label Uses:
   • Bone and joint infections.
   • Central nervous system (CNS) infections (e.g., meningitis) caused by susceptible organisms.

Linezolid is available in both intravenous (IV) and oral formulations. The oral formulation has excellent bioavailability (approximately 100%), allowing for seamless transition from IV to oral therapy.

Adults:

• Standard dose: 600 mg every 12 hours (IV or oral) for 10–14 days, depending on the infection.
• Duration of therapy:
  • Skin and soft tissue infections: 10–14 days.
  • Pneumonia: 10–14 days.
  • VRE infections: 14–28 days.

Children:

• Neonates (0–7 days): 10 mg/kg every 12 hours.
• Neonates (8–28 days): 10 mg/kg every 8 hours.
• Children (>28 days): 10 mg/kg every 8 hours (maximum 600 mg per dose).

Renal and Hepatic Impairment:

• No dose adjustment is required for renal or hepatic impairment. However, caution is advised in patients with severe hepatic impairment.

Linezolid is generally well-tolerated, but it can cause several adverse effects, particularly with prolonged use (beyond 28 days):

1. Hematologic Effects:
   • Thrombocytopenia (low platelet count) is the most common side effect.
   • Anemia and leukopenia may also occur.
   • Monitor complete blood counts (CBC) weekly, especially during prolonged therapy.
2. Gastrointestinal Effects:
   • Nausea, vomiting, diarrhea, and abdominal pain.
3. Neuropathy:
   • Peripheral neuropathy and optic neuropathy may occur with prolonged use.
   • Patients should be advised to report symptoms such as numbness, tingling, or vision changes.
4. Lactic Acidosis:
   • Rare but serious side effect due to mitochondrial toxicity.
   • Symptoms include nausea, vomiting, abdominal pain, and unexplained acidosis.
5. Serotonin Syndrome:
   • Linezolid is a weak monoamine oxidase inhibitor (MAOI) and can interact with serotonergic drugs, leading to serotonin syndrome.
   • Symptoms include agitation, confusion, hyperreflexia, and hyperthermia.
6. Allergic Reactions:
   • Rash, pruritus, and, rarely, anaphylaxis.

1. Duration of Therapy:
   • Limit use to the shortest duration necessary to reduce the risk of adverse effects, particularly hematologic and neurologic toxicity.
2. Hematologic Monitoring:
   • Monitor CBC weekly, especially in patients receiving therapy for more than 2 weeks.
3. Serotonin Syndrome:
   • Avoid concurrent use with serotonergic drugs (e.g., SSRIs, SNRIs, TCAs, MAOIs).
4. Pregnancy and Lactation:
   • Use only if clearly needed. Limited data are available on safety during pregnancy and lactation.
5. Myelosuppression:
   • Use with caution in patients with pre-existing bone marrow suppression or those receiving myelosuppressive drugs.
6. Drug Resistance:
   • Overuse or inappropriate use of linezolid can lead to the development of resistant bacteria.

Linezolid has several clinically significant drug interactions due to its MAOI activity and potential for serotonin syndrome:

1. Serotonergic Drugs:
   • SSRIs (e.g., fluoxetine, sertraline): Increased risk of serotonin syndrome.
   • SNRIs (e.g., venlafaxine, duloxetine): Increased risk of serotonin syndrome.
   • TCAs (e.g., amitriptyline): Increased risk of serotonin syndrome.
   • MAOIs (e.g., phenelzine): Contraindicated due to severe risk of serotonin syndrome.
2. Adrenergic Agents:
   • Increased risk of hypertensive crisis with sympathomimetic drugs (e.g., pseudoephedrine).
3. Tyramine-Rich Foods:
   • Avoid excessive consumption of tyramine-rich foods (e.g., aged cheese, cured meats) to prevent hypertensive crisis.
4. Other Interactions:
   • Rifampin: May reduce linezolid levels due to induction of metabolism.

Warfarin: Monitor INR closely, as linezolid may enhance anticoagulant effects.

Linezolid is available under various generic names, including:

• Linezolid

It is marketed under the brand name Zyvox.