macrolide, class of antibiotics characterized by their large lactone ring structures and by their growth-inhibiting (bacteriostatic) effects on bacteria. The macrolides were first discovered in the 1950s, when scientists isolated erythromycin from the soil bacterium Streptomyces erythraeus. In the 1970s and 1980s synthetic derivatives of erythromycin, including clarithromycin and azithromycin, were developed.
Macrolides are usually administered orally, but they can be given parenterally. These drugs are valuable in treating pharyngitis and pneumonia caused by Streptococcus in persons sensitive to penicillin. They are used in treating pneumonias caused either by Mycoplasma species or by Legionella pneumophila (the organism that causes Legionnaire disease); they are also used in treating pharyngeal carriers of Corynebacterium diphtheriae, the bacillus responsible for diphtheria.
Macrolides work by binding to a specific subunit of ribosomes (sites of protein synthesis) in susceptible bacteria, thereby inhibiting the formation of bacterial proteins. In most organisms this action inhibits cell growth; however, in high concentrations it can cause cell death. Some species of bacteria, including Streptococcus pneumoniae and Staphylococcus aureus, have been found to carry mutations that alter the macrolide binding site on the ribosomal subunit, which renders the bacteria resistant to the agents. Other mechanisms of resistance to macrolides, including the activation of drug efflux proteins and the production of drug-inactivating enzymes, also have emerged in some strains of bacteria.
Minor side effects of macrolides include nausea, vomiting, diarrhea, and ringing or buzzing in the ears (tinnitus). Serious side effects, including allergic reaction and cholestatic hepatitis (inflammation and congestion of bile ducts in the liver), are generally associated only with the use of erythromycin. Macrolides also have important drug interactions that can lead to adverse affects on the heart.