Azalides

Azalides are a subclass of macrolide antibiotics characterized by a modified macrolactone ring containing a nitrogen atom, which typically yields a 15-membered ring structure. They were developed from erythromycin to improve acid stability, oral bioavailability and tissue penetration while retaining the macrolide antibacterial mechanism.

Chemistry and mechanism

The defining chemical change in azalides is the insertion of an aza (nitrogen-containing) group into the macrolide core. Like other macrolides, azalides bind to the 50S subunit of the bacterial ribosome (23S rRNA) and inhibit protein synthesis by blocking translocation. This action is primarily bacteriostatic, but can be bactericidal against some susceptible organisms at higher concentrations.

Pharmacology

Azalides have favorable pharmacokinetics, including enhanced acid stability, extensive tissue and intracellular accumulation, and prolonged half-lives that allow short-course or once-daily dosing. They generally show fewer interactions with cytochrome P450 enzymes than older macrolides, though class-specific cardiac effects can occur.

Clinical use

The prototype and most widely used azalide is azithromycin. Azalides are employed in respiratory tract infections, certain skin and soft-tissue infections, and infections caused by atypical organisms such as Mycoplasma, Chlamydia and Legionella. They are also used in some combination regimens for sexually transmitted infections and other indications.

Adverse effects and resistance

Common adverse effects include gastrointestinal symptoms such as nausea and diarrhea; azalides can also prolong the QT interval in susceptible patients. Bacterial resistance arises via target site modification (methylation), efflux pumps, and enzymatic inactivation, limiting efficacy in some settings. Clinical choice depends on local susceptibility patterns and individual patient considerations.