Macrolides

Erythromycin was discovered in 1952. It is derived from the Streptomyces fungus. It is bacteriostatic against Staphylococcus aureus and Streptococcus spp. and may be bacteriocidal in high concentrations. It works by inhibiting protein synthesis. There may also be some activity against Pseudomonas spp.¹ Macrolides also have a well documented anti-inflammatory action, by reducing cytokine production and also reducing neutrophil migration.² This broadens their role in the management of respiratory disease.

• Erythromycin
• Clarithromycin:
  • Has a slightly broader spectrum than erythromycin.
  • Tissue levels are higher and it is given twice daily.
• Azithromycin:
  • This has greater efficacy against gram negative bacteria e.g. H. Influenzae, but is not as effective against gram positive bacteria when compared to erythromycin.
  • It produces high tissue concentrations, with a long half-life and is given as a once daily dose.
• Spiramycin

Telithromycin is a ketolide. It is derived from erythromycin, with a similar antibacterial spectrum, although it is also effective against both the major (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and atypical/intracellular (Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) community acquired pneumonia pathogens.³

• Known hypersensitivity to macrolides.
• Co-administration of cisapride, pimozide, terfenedine or ergot derivatives:
  • Cardiac arrhythmias have occurred e.g. prolonged QT interval, ventricular fibrillation or ventricular tachycardia and torsades de pointes. There have been fatalities.
  • The problem is thought to be due to the macrolides inhibiting the hepatic metabolism of these drugs.
• They should be used with caution in hepatic impairment.

Nausea, vomiting and diarrhoea in some patients:

• If the infection is mild, giving a lower dose. e.g. 250 mg four times daily may avoid this.
• If a more serious infection is suspected, a higher dose is necessary - see individual formulary.
• Clarithromycin and azithromycin both cause fewer GI side-effects than erythromycin.