What is the mechanism of action of erythromycin?

Mechanism of Action of Erythromycin

Erythromycin works by inhibiting bacterial protein synthesis through binding to the 50S ribosomal subunit, preventing RNA-dependent protein synthesis in susceptible bacteria. 1, 2

Primary Mechanism

Erythromycin belongs to the macrolide class of antibiotics and exerts its antimicrobial effect through the following mechanisms:

• Ribosomal binding: Specifically binds to the 50S ribosomal subunit of bacteria 1
• Protein synthesis inhibition: Blocks the translocation reaction during protein synthesis 3
• Site of action: Binds at the polypeptide exit region of the bacterial ribosome 1
• Effect on bacteria: Generally bacteriostatic, but can be bactericidal against autolytic species such as pneumococci 1

Antimicrobial Spectrum

Erythromycin demonstrates activity against:

• Gram-positive bacteria:

  • Staphylococcus aureus (though resistant organisms may emerge during treatment)
  • Streptococcus pneumoniae
  • Streptococcus pyogenes
  • Corynebacterium species
  • Listeria monocytogenes 2

• Gram-negative bacteria:

  • Bordetella pertussis
  • Haemophilus influenzae
  • Legionella pneumophila
  • Neisseria gonorrhoeae
  • Moraxella catarrhalis 2, 3

• Other microorganisms:

  • Mycoplasma pneumoniae
  • Chlamydia trachomatis
  • Treponema pallidum
  • Ureaplasma urealyticum 2

Pharmacokinetic Considerations

Several important pharmacokinetic properties influence erythromycin's effectiveness:

• Absorption: Readily absorbed orally in microbiologically active form, though individual variations exist 2
• Distribution: Diffuses readily into most body fluids and crosses the placental barrier 2
• Protein binding: Largely bound to plasma proteins 2
• Cellular concentration: Actively concentrated intracellularly by polymorphonuclear leukocytes and alveolar macrophages 3
• pH sensitivity: Exhibits better antibacterial activity in neutral to basic pH environments 1
• Elimination: Primarily concentrated in the liver and excreted in bile; less than 5% recovered in active form in urine 2

Clinical Implications

Understanding erythromycin's mechanism of action has important clinical implications:

• Resistance development: Bacterial resistance can develop through:

  • Modification of the 23S rRNA in the 50S ribosomal subunit
  • Efflux mechanisms
  • Plasmid-mediated resistance 1, 2

• Drug interactions:

  • Antagonism exists between erythromycin and clindamycin, lincomycin, and chloramphenicol 2
  • Inhibits cytochrome P450 enzymes (CYP3A), potentially increasing concentrations of many drugs 1

• Administration considerations:

  • Optimal blood levels achieved when taken in the fasting state (at least 30 minutes and preferably 2 hours before meals) 2
  • For dental prophylaxis, can be used as an alternative in penicillin-allergic patients 4

Common Pitfalls and Caveats

• Resistance concerns: Rising bacterial resistance rates to macrolides have been reported globally, with S. pneumoniae resistance varying from <10% to >90% between countries 1
• Cross-resistance: Resistance to erythromycin often confers cross-resistance to other macrolides 1
• Adverse effects:
  • Gastrointestinal irritation (epigastric distress, abdominal cramps, nausea, vomiting, diarrhea) 1
  • Risk of infantile hypertrophic pyloric stenosis in neonates 1
  • QT prolongation and cardiac arrhythmias with certain drug combinations 1
• Formulation limitations: Very low solubility in water and instability under acidic conditions cause limited efficacy and bioavailability 5

Understanding erythromycin's mechanism of action helps clinicians optimize its use while minimizing the risk of resistance development and adverse effects.