Macrolides and Ketolides
Macrolides and ketolides are classes of antibiotics that inhibit bacterial protein synthesis. While macrolides are older and widely used, ketolides are a newer subclass with improved activity against resistant strains, particularly respiratory pathogens.
Classification / Examples
- Macrolides: Erythromycin, Azithromycin, Clarithromycin, Spiramycin
- Ketolides: Telithromycin (the only clinically approved ketolide)
Pharmacodynamics
Macrolides and ketolides inhibit bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome, specifically at the P site. This prevents translocation of the ribosome along the mRNA, blocking the addition of new amino acids to the nascent peptide chain and halting protein synthesis.
- Macrolides are primarily bacteriostatic, but may be bactericidal at high concentrations or against highly susceptible organisms.
- Ketolides bind more tightly to the 50S subunit and are more potent, especially against macrolide-resistant strains.
- Spectrum of activity:
- Macrolides: Gram-positive cocci (e.g. Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus), atypicals (e.g. Mycoplasma, Chlamydia, Legionella)
- Ketolides: Broader activity including macrolide-resistant Streptococcus pneumoniae
Side Effects
- Common:
- GI upset (nausea, vomiting, diarrhea)
- Visual disturbances (telithromycin)
- Metallic taste (clarithromycin)
- Serious:
- Cardiotoxicity (QT prolongation → risk of arrhythmia)
- Hepatotoxicity (esp. erythromycin estolate)
- Hypersensitivity reactions (rash, anaphylaxis)
- Hearing loss (reversible, dose-related)
- Resistance mechanisms:
- Ribosomal methylation (erm gene)
- Efflux pumps (mef gene)
- Target site mutations