Macrolides

Summary

Macrolides are a class of antibiotics that end in the suffix “-thromycin”: including azithromycin, clarithromycin, and erythromycin. Macrolides work by inhibiting the 50S subunit of bacterial ribosomes, stopping protein production to inhibit bacterial growth. Clinically, macrolides are used for a wide variety of bacterial infections, including the treatment of atypical pneumonias from organisms like Legionella or Mycoplasma, as well as treatment of sexually-transmitted infections like chlamydia and gonorrhoea. Important adverse effects to know include hepatitis, GI upset, and QT prolongation, with a risk of causing Torsades de Pointes. It’s also extremely important to remember that macrolides can cause drug interactions by inhibiting CYP enzymes in the liver.

Key Points

• Macrolides
  • Drug Names (-thromycin ending)
    • Azithromycin
    • Clarithromycin
    • Erythromycin
  • Mechanism
    • Bind to 50S subunit of bacterial ribosomes
      • Bind to the 23S rRNA of the 50S ribosomal subunit, to blocking transpeptidation, translocation, and chain elongation
      • Overall effect is a blocking of bacterial protein synthesis
    • Bacteriostatic
  • Clinical Use
    • Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
    • STIs (Chlamydia, N. gonorrhoae)
    • Bordetella pertussis
    • Gram-positive cocci (streptococcal) in patients allergic to penicillin
  • Adverse Effects
    • Inhibits CYP450 Enzymes
      • Leads to drug interactions (e.g. warfarin, theophylline)
    • GI Upset
      • All macrolides act as agonists at motilin receptors in the GI tract, increasing GI motility
    • Prolonged QT interval (Torsades de Pointes risk)
    • Acute cholestatic hepatitis
    • Rash
    • Eosinophilia
  • Mechanism of Resistance
    • Methylation of 23S rRNA-binding site prevents binding of drug