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Linezolid

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First of a new class of synthetic antibacterials: oxazolidinones

Mode of action

  • Inhibits ribosomal protein synthesis by inhibiting formation of the initiation complex

Spectrum of activity

  • in vitro activity against most pathogenic Gram positives
    • bacteriostatic against most organisms but bacteriacidal against pneumococcus
    • spectrum of activity includes MRSA and vancomycin resistant enterococci
    • borderline activity against Bacteroides fragilis
    • clinical efficacy similar to vancomycin for pneumonia and complicated soft tissue infections
  • relatively good in vitro activity against mycobacteria including Mycobacterium tuberculosis and Mycobacterium avium complex. Clinical significance of this activity unknown
  • excellent in vitro activity against Nocardia species
  • sub-inhibitory concentrations inhibit expression of virulence factors by staphylococci and streptococci and potentiate susceptibility of S. aureus and Strep. pyogenes to phagocytosis by neutrophils

Pharmacokinetics

  • Administration: IV or PO (100% bioavailability in healthy volunteers)
  • Wide tissue distribution
    • good lung penetration: concentration in epithelial lining fluid 4.5 x plasma
    • CSF penetration much better than vancomycin
    • ~30% protein bound
  • Elimination by predominantly by hepatic metabolism, although 30-35% excreted unchanged in urine
    • parent drug does not accumulate significantly in renal failure but metabolites do. Clinical significance of this unknown.
    • elimination half life ~4.5-5.5 h
    • both linezolid and metabolites eliminated by haemodialysis
    • no dosage adjustment recommended for patients with renal and hepatic insufficiency but inadequate data on patients with severe hepatic insufficiency to be sure this recommendation applies to these patients.
  • Dosage adjustment for critical illness not necessary
  • Efficacy associated with ratio of area under concentration-time curve to MIC

Clinical uses

  • complicated skin and soft tissue infections caused by S. aureus (MRSA or MSSA), Strep. pyogenes or Strep. agalactiae
  • uncomplicated skin infections caused by MSSA or Strep. pyogenes
  • nosocomial pneumonia caused by S. aureus (MRSA or MSSA) or Strep. pneumoniae
  • infections with glycopeptide resistant enterococci or staphylococci
  • although clinical trials suggest that the efficacy of linezolid and vancomycin are similar for patients with MRSA infection a meta-analysis with sub-group analysis suggests that linezolid may be more effective for nosocomial pneumonia.  Further subgroup analysis suggests that linezolid is more effective in ventilator associated pneumonia

Adverse effects

  • not nephrotoxic
  • myelosuppression causing anaemia, leucopaenia, pancytopaenia and thrombocytopaenia. More common in:
    • patients receiving >2 weeks of linezolid
    • pre-existing myelosuppression
    • concomitant administration of drugs which cause myelosuppression
    • chronic infection in patients who have received previous or concomitant antibiotics
  • lactic acidosis (rare)

Drug interactions

  • co-administration of serotinergic agents (eg MAOI) may result in serotonin syndrome (rare)
  • adrenergic agents, resulting in hypertension

Further reading

Moellering RC. Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med, 2003; 138:135-42

Kolleff M et al. Intensive Care Medicine, 2004

Potential conflict of interest

The Dept of Anaesthesia & Intensive Care, The Chinese University of Hong Kong received sponsorship for educational activities from Pharmacia in 2002 and Pfizer Corp. Hong Kong Ltd. in 2003 and 2004


©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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