Macrolides

Macrolides are a class of antibiotics characterized by a large macrocyclic lactone ring. The most commonly used members are erythromycin, azithromycin, and clarithromycin. They act by reversibly binding to the 50S subunit of the bacterial ribosome, inhibiting translocation and thereby blocking peptide chain elongation. Most macrolides are bacteriostatic, but they can be bactericidal at high concentrations or against certain organisms.

The spectrum of activity includes many gram-positive cocci (such as Streptococcus species and Staphylococcus aureus), atypical pathogens (Mycoplasma pneumoniae, Chlamydophila species, Legionella), and some gram-negative organisms like Haemophilus influenzae. Activity against Enterobacterales is limited and waning for some agents. Azithromycin and clarithromycin often have improved activity against certain atypicals and Haemophilus compared with erythromycin. Macrolides are frequently used as alternatives for patients with penicillin allergies and for infections where atypical pathogens are suspected.

Pharmacokinetics and interactions vary by drug. Erythromycin has relatively low oral bioavailability and significant gastrointestinal effects; azithromycin and clarithromycin have better absorption and tissue distribution and longer half-lives, enabling shorter courses or once-daily dosing in some regimens. All macrolides can interact with other medications via cytochrome P450 enzymes (especially erythromycin and clarithromycin) and may prolong the QT interval, particularly with other QT-prolonging drugs.

Resistance mechanisms include target-site methylation, efflux pumps, and enzymatic inactivation, leading to MLS_B-type resistance and cross-resistance with related antibiotics.