macrolide

Macrolides are a class of antibiotics characterized by a large macrocyclic lactone ring, typically containing 12, 14, or 16 members. The group includes erythromycin, azithromycin, clarithromycin, roxithromycin, spiramycin, and related compounds. Erythromycin was the first macrolide to be discovered in 1952 from the actinomycete Saccharopolyspora erythraea.

Mechanism of action: Macrolides bind reversibly to the 50S ribosomal subunit and inhibit the translocation step of protein synthesis, preventing peptide chain elongation. They are generally bacteriostatic, though they can be bactericidal against certain organisms at higher concentrations.

Spectrum and uses: They are active against many gram-positive cocci (such as Streptococcus pneumoniae and Streptococcus pyogenes), some gram-negative bacteria (notably Haemophilus influenzae), and atypical pathogens including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila. Clinically, macrolides are used for respiratory tract infections, otitis media, sinusitis, atypical pneumonia, certain skin infections, and, in some cases, sexually transmitted infections, where coinfection with Chlamydia is a consideration.

Pharmacokinetics and interactions: Azithromycin and clarithromycin have improved oral bioavailability and tissue penetration, with azithromycin featuring a long half-life suitable for once-daily dosing. Erythromycin is more acid-labile and commonly associated with gastrointestinal side effects. Macrolides can interact with other drugs via cytochrome P450 inhibition (notably erythromycin and clarithromycin), affecting statins, anticoagulants, and other medications.

Resistance and safety: Resistance arises through methylation of the 23S rRNA target and efflux mechanisms. Adverse effects include gastrointestinal upset, rare hepatotoxicity, and QT interval prolongation, which can predispose to arrhythmias when combined with other QT-prolonging drugs. Fidaxomicin is a related macrocyclic antibiotic but is not classified as a macrolide.