The macrolides are a group of drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring, a large lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring can be either 14, 15 or 16-membered. Macrolides belong to the polyketide class of natural products.

Members

The most commonly-prescribed macrolide antibiotics are:

• erythromycin
• clarithromycin
• azithromycin
• roxithromycin

Others are: spiramycin (used for treating toxoplasmosis), ansamycin, oleandomycin, carbomycin and tylocine.

There is also a new class of antibiotics called ketolides that is structurally related to the macrolides. Ketolides such as telithromycin are used to fight respiratory tract infections caused by macrolide-resistant bacteria.

Non-antibiotic macrolides

The drug Tacrolimus, which is used as an immunosuppresant, is also a macrolide. It has similar activity to cyclosporine. While it does have antibiotic properties, it is not approved for antibiotic usage due to its strong effects on the immune system.

Uses

Macrolides are used to treat infections such as respiratory tract infections and soft tissue infections. The antimicrobial spectrum of macrolides is slightly wider than that of penicillin. Beta-hemolytic streptococci, pneumococci, staphylococci and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have shown effective against mycoplasma, mycobacteria, some rickettsia and chlamydia.

Mechanism of action

The mechanism of action of the macrolides is inhibition of bacterial protein synthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations. Macrolides tend to accumulate within leucocytes, and are therefore actually transported into the site of infection.

Resistance

Bacterial resistance to macrolides occurs by alteration of the structure of the bacterial ribosome. This resistance can be either plasmid-mediated or chromosomal, i.e through mutation.