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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.

Available treatments
  • 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

Indications

Where possible treatment should be indicated by sensitivity from a cultured specimen. If empirical treatment is required, your local primary care trust formulary should have recommended treatments based on knowledge of local prevalent pathogens and resistance.

Cautions and contra-indications
Adverse effects

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.

Document references
  1. Tateda K, Ishii Y, Matsumoto T, et al; Direct evidence for antipseudomonal activity of macrolides: exposure-dependent bactericidal activity and inhibition of protein synthesis by erythromycin, clarithromycin, and azithromycin. Antimicrob Agents Chemother. 1996 Oct;40(10):2271-5. [abstract]
  2. Khair OA, Devalia JL, Abdelaziz MM, et al; Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J. 1995 Sep;8(9):1451-7. [abstract]
  3. Brown SD; Benefit-risk assessment of telithromycin in the treatment of community-acquired pneumonia. Drug Saf. 2008;31(7):561-75. [abstract]
  4. RSM; Macrolides and Cystic Fibrosis. Royal Society of Medicine.
  5. Stover DE, Mangino D; Macrolides: a treatment alternative for bronchiolitis obliterans organizing pneumonia? Chest. 2005 Nov;128(5):3611-7. [abstract]
  6. Bell SC, Senini SL, McCormack JG; Macrolides in cystic fibrosis. Chron Respir Dis. 2005;2(2):85-98. [abstract]
Internet and further reading AcknowledgementsEMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 353
Document Version: 2
DocRef: bgp25097
Last Updated: 15 Jul 2008
Review Date: 15 Jul 2009










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