Linezolid

Submitted by amh10 on 8 July, 2006 - 17:33

This belongs to the group: Oxazolidinones. Linezolid is the only member of this group.  

Absorption: PO, IV. 100% PO bioavailability.
 
Distribution: Good tissue penetration & CSF penetration. 31% protein bound.  

Metabolism: Hepatic, ↓ in severe liver failure.  Elimination: Renal, no need to ↓ in CRF.
 
Mechanism: Inhibition of protein synthesis, by binding to the 50S subunit of ribosomes. The initiation complex is interrupted thus preventing translation. It is bacteriostatic. 

 

linezolid

 

Resistance:

  1. Target site modification (e.g. mecA, enterococci)
  2. Acquire a new target site
  3. Production of enzyme to inactivate antibiotic
  4. Impermeability
  5. ↑efflux

In the case of linezolid, target site modification is virtually the only mechanism of resistance that has thus far been described. Mutations identified in various species are associated with G to U substitution in the peptidyl transferase center of 23S rRNA at position 2576 and result in reduced affinity of linezolid to the 50S subunit. This and other sites of mutations (e.g. T2500A in S. aureus) lie in the proximity of P site, which confirms the mechanism of action of oxazolidinones. In addition, one report describes a non-ribosomal mechanism of resistance in Mycobacterium smegmatis. Ribosomes isolated from these strains behaved essentially like wild-type ribosomes in the presence of drug. It is speculated that the resistance may arise from decreased uptake or increased efflux of the drug.

Antimicrobial spectrum: Mostly Gm (+).

Toxicity & S/E: After 2 weeks - ↓FBC due to marrow suppression. Interactions with MAOI.

Clinical Use: CAP, VAP, complicated skin & soft tissue infections (MRSA, VRE & penicillin ® pneumococci). Endophthalmitis? Intra-vitreous injections. EXPENSIVE+++, Consultant only prescription.

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