Linezolid

LINEZOLID

• Synthetic antibiotic agent of oxazolidinone class of antibiotics.
• Acts by inhibiting protein synthesis.
• Used for treatment of serious infections due to multi-resistant Gram-positive bacteria.
• Includes Methicillin-resistant Staphylococcus aureus (MRSA).
• Vancomycin-resistant enterococci (VRE).
• Also categorized under reversible, nonselective monoamine oxidase inhibitor. 
• Hence, has potential for interaction with adrenergic & serotonergic agents.

• In-vitro activity against aerobic gram-positive bacteria, certain gram-negative bacteria & anaerobic microorganisms.
• Effective against all clinically important gram-positive bacteria.
• Enterococcus faecium & Enterococcus faecalis (including vancomycin-resistant enterococci).
• Staphylococcus aureus (including MRSA).
• Streptococcus agalactiae, Streptococcus pneumoniae, & Streptococcus pyogenes
• No effect on Gram-negative bacteria. 
• Bacteriostatic – Against enterococci and staphylococci. 
• Bactericidal – For streptococci for majority of strains. 

Protein synthesis inhibitor: 

• Acts on first step of protein synthesis, Ie. ‘initiation’.
• Unlike other protein synthesis inhibitors inhibiting elongation.
• Binds to 23S portion of 50S subunit (center of peptidyl transferase activity).
• Prevents formation of functional 70S-initiation complex. 
• Linezolid resistance due to mutation of 23S ribosomal RNA has been detected among enterococci.

INDICATION:

• Bacterial infections caused by susceptible strains of vancomycin-resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumonia, Streptococcus pyogenes & Streptococcus agalactiae.
• Community-Acquired Pneumonia (CAP)
• Bacterial infections.
• Skin & subcutaneous tissue bacterial infections
• Uncomplicated skin & skin structure infections
• Hospital-acquired bacterial pneumonia

 ADVERSE EFFECT:

• Principal toxicity – Hematologic.
• Is reversible & generally mild.
• Thrombocytopenia – Most common manifestation.
• Seen in approx. 3% of treatment courses.
• Particularly when administered for longer than 2 weeks. 
• Platelet count should be monitored.
• Anaemia.
• Neutropenia 
• May underly bone marrow suppression.
• Causes optic & peripheral neuropathy and lactic acidosis on prolonged use.
• Due to linezolid-induced inhibition of mitochondrial protein synthesis.

• Interactions seen with,
• Adrenergic/Serotonergic drugs (SSRIs, etc.).
• Excess dietary tyramine.
• Because linezolid is MAO inhibitor.