Oxazolidinones

crop_square Key points

  • check_circle Bacteriostatic synthetic antibiotics with a core of five-membered heterocyclic rings
  • check_circle Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit
  • check_circle Excellent activity against gram-positives including multi-drug resistant organisms
  • check_circle Last-line antibiotics as resistances are still rare

crop_square Background and biochemistry

Oxazolidinones are a relatively new class of synthetic antibiotics. The best-known drug currently in clinical use is linezolid. Promising drug candidates are in development. All oxazolidinones share a core structure consisting of five-membered heterocyclic rings.

crop_square Mechanism of action

Oxazolidinones interfere with bacterial protein synthesis. They bind to the 23S ribosomal RNA of the 50S bacterial ribosome subunit. This prevents the formation of the initiation complex, a structure essential for bacterial protein biosynthesis. Linezolid is considered a bacteriostatic antibiotic but may have a limited bactericidal effect against certain bacteria. Resistance mechanism include efflux pumps reducing the intracellular drug level and mutations at the binding site. Currently, resistances against linezolid are still rare.

crop_square Drugs and spectrum of activity

  • Line­zolid
  • Tedi­zolid

Oxazolidinones are very active against gram-positive organisms, including many multi-drug resistant strains. They show excellent activity against mycobacteria, and linezolid may be used for treatment of multi-drug resistant tuberculosis. It should be noted that clinical data are still scarce. Tedizolid is primarily used to treat acute skin infections.

crop_square Pharmacokinetics

Bioavailability, tissue and CSF penetration are excellent after oral administration. Linezolid and tedizolid are metabolised by the liver and excreted primarily by the kidneys (linezolid) or via faeces (tedizolid).

crop_square Adverse drug effects

Known adverse effects include vomiting, nausea, diarrhoea and reversible thrombocytopenia.