What is a macrolide?

What is a Macrolide?

Macrolides are a class of antibiotics characterized by a macrocyclic lactone ring of 12 or more elements, with the most commonly used varieties having 14-membered or 15-membered lactone rings. 1

Key Characteristics of Macrolides

• Macrolides include a variety of drugs such as antibiotics, antifungals, prokinetic agents, and immunosuppressants, all sharing the common macrocyclic lactone ring structure 1

• The first macrolide, erythromycin, was launched commercially in 1952, while newer macrolides like clarithromycin (14-membered) and azithromycin (15-membered) became available in the 1980s 1, 2

• Macrolides are active orally and have excellent tissue penetration, making them effective for treating various infections 1

Mechanism of Action

• Macrolides bind to the 23S rRNA of the bacterial 50S ribosomal subunit, inhibiting RNA-dependent protein synthesis by blocking the polypeptide exit region 1, 3

• While generally considered bacteriostatic, macrolides can be bactericidal against autolytic species such as pneumococci 1

• Beyond their antimicrobial effects, macrolides possess immunomodulatory properties that include:

  • Alterations in airway secretions through effects on ion transport and mucus production 1
  • Changes in inflammatory processes via effects on cytokine production and adhesion molecule expression 1
  • Sublethal effects on bacteria including disruption of biofilms and interference with quorum sensing 1

Antimicrobial Spectrum

• Macrolides demonstrate antimicrobial activity against:

  • Many Gram-positive bacteria (especially Streptococcus pneumoniae) 1, 4
  • Some Gram-negative organisms 1
  • "Atypical" respiratory pathogens such as Legionella and Mycoplasma 1, 4
  • Some mycobacterial species 1

• Newer macrolides like clarithromycin and azithromycin have improved activity against Haemophilus influenzae compared to erythromycin 5, 6

Clinical Applications

• Macrolides are commonly used for:

  • Respiratory tract infections including community-acquired pneumonia 4, 5
  • Skin and soft tissue infections 2, 4
  • Sexually transmitted diseases (particularly azithromycin for chlamydia) 1, 7
  • Gastrointestinal infections (e.g., Campylobacter diarrhea) 1, 4

• Specific macrolides have unique applications:

  • Clarithromycin is effective for treatment and prophylaxis of Mycobacterium avium complex (MAC) in AIDS patients 7
  • Azithromycin is preferred for Chlamydia trachomatis infections 7
  • Clarithromycin is indicated for acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, and community-acquired pneumonia in adults 8

Pharmacokinetic Considerations

• Macrolides exhibit varying pharmacokinetic parameters:
  • Bioavailability ranges from 25% to 85% 5
  • Half-lives vary from short (erythromycin) to medium (clarithromycin) to very long (azithromycin) 5
  • All macrolides display large volumes of distribution with excellent uptake into respiratory tissues 5

Cautions and Considerations

• Rising antimicrobial resistance is a significant concern with macrolide use, particularly in Streptococcus pneumoniae 1

• Macrolide resistance can develop through several mechanisms including target site alteration, altered antibiotic transport, and modification of the antibiotic 5

• Special caution is needed when considering macrolides in patients with non-tuberculous mycobacterial (NTM) infections, as resistance can develop through single point mutations 1

• The risks of increasing antimicrobial resistance should be discussed with patients prior to starting low-dose macrolide therapy 1