Macrolides

Macrolides: Introduction

Macrolides are a class of broad-spectrum antibiotics characterized by a macrocyclic lactone ring in their chemical structure. They are widely used to treat bacterial infections, especially in patients who are allergic to penicillin, and are particularly effective against Gram-positive bacteria and some atypical pathogens.

History

• The first macrolide, erythromycin, was discovered in 1952 from Saccharopolyspora erythraea.

• Since then, semi-synthetic macrolides like azithromycin and clarithromycin were developed to improve stability, absorption, and tolerability.

Mechanism of Action

• Macrolides bind to the 50S subunit of bacterial ribosomes.

• This inhibits protein synthesis, preventing bacteria from growing and multiplying.

• Depending on the concentration and bacterial species, macrolides can be bacteriostatic (inhibit growth) or, in some cases, bactericidal.

Spectrum of Activity

• Gram-positive bacteria: Streptococcus species, Staphylococcus aureus (some strains)

• Atypical bacteria: Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila

• Some Gram-negative bacteria: Haemophilus influenzae, Neisseria gonorrhoeae

• Other organisms: Certain Helicobacter pylori strains (used in combination therapy)

Common Uses

• Respiratory tract infections: Pneumonia, bronchitis, sinusitis

• Skin and soft tissue infections: Cellulitis, acne (especially with erythromycin or azithromycin)

• Sexually transmitted infections: Chlamydia, gonorrhea (in combination therapy)

• H. pylori eradication (as part of triple therapy for peptic ulcer disease)

• Pertussis (whooping cough)

Advantages

• Effective alternative for penicillin-allergic patients

• Good tissue penetration, especially in the lungs

• Convenient dosing schedules for newer macrolides (e.g., azithromycin)

Risks and Concerns

• Gastrointestinal side effects: Nausea, vomiting, diarrhea (common with erythromycin)

• Cardiac effects: Prolonged QT interval, which can increase risk of arrhythmias

• Drug interactions: Inhibit cytochrome P450 enzymes (especially erythromycin and clarithromycin), affecting drugs like warfarin, statins, and certain anticonvulsants

• Resistance: Increasing resistance among Streptococcus and Staphylococcus species

Examples of Macrolides

• Erythromycin – first-generation, widely used but may cause GI irritation

• Clarithromycin – improved absorption and stability

• Azithromycin – long half-life, convenient once-daily dosing

• Roxithromycin – similar to erythromycin with better tolerability