Linezolid

INTRODUCTION:
  • It is a synthetic antibiotic used for the treatment of serious infections caused by multi-resistant Gram-positive bacteria, including.Methicillin-resistant Staphylococcus aureus (MRSA). 
  1. Streptococci,
  2. Vancomycin-resistant enterococci (VRE),
  • Linezolid is a protein synthesis inhibitor: 
  1. Unlike most other protein synthesis inhibitors, which inhibit elongation, linezolid appears to work on the first step of protein synthesis, i.e. 'initiation'
  2. Linezolid binds to the 23S portion of the 50S subunit (the center of peptidyl transferase activity) 
  3. Linezolid is effective against all clinically important Gram-positive bacteria, notably Enterococcus faecium and Enterococcus faecalis (including vancomycin-resistant enterococci), Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus, MRSA), Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes
  4. It has almost no effect on Gram-negative bacteria. 
INDICATION:
  • Bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.
  • Community Acquired Pneumonia (CAP)
  • Infections, Bacterial
  • Skin and Subcutaneous Tissue Bacterial Infections
  • Uncomplicated Skin and Skin Structure Infections
  • Hospital-acquired bacterial pneumonia
MECHANISM OF ACTION:
  • Linezolid is a synthetic antibacterial agent of the oxazolidinone class of antibiotics.
  • It has in vitro activity against aerobic Gram positive bacteria, certain Gram negative bacteria and anaerobic microorganisms.
  • It selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. 
  • Specifically, linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. 
  • The results of time-kill studies have shown linezolid to be bacteriostatic against enterococci and staphylococci. 
  • For streptococci, linezolid was found to be bactericidal for the majority of strains. 
  • Linezolid is also a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.
ADVERSE EFFECT:
  • The principal toxicity of linezolid is hematologic—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. Thus Platelet count should be monitored in patient receiving linezolid therapy 
  • 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.
Exam Question
  • Platelet count should be monitored in patient receiving linezolid therapy
  • Optic neuropathy ,Pancytopenia & Lactic acidosis are side effects of Linezolid 
  • In Methicillin - resistant staphylococcus - aureus (MRSA) linezolid can be given

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