Practical information on using macrolides

The macrolides azithromycin, clarithromycin, erythromycin and roxithromycin have a broad spectrum of activity, including activity against gram-positive cocci, Corynebacterium species, gram-negative cocci, and Legionella, Mycoplasma and Chlamydia species, as well as some gram-positive and gram-negative anaerobic bacteria. Erythromycin, azithromycin and clarithromycin are also active against Bordetella pertussis.

Unlike other macrolides, clarithromycin has a microbiologically active metabolite. Clarithromycin is active against nontuberculous mycobacteria, including Mycobacterium avium complex (MAC), and is used in combination with other drugs for this indication. It is also used in combination with other drugs for eradication of Helicobacter pylori.

Azithromycin is less active than erythromycin against gram-positive bacteria but has a broader range of gram-negative activity (eg Salmonella species). Azithromycin is also active against nontuberculous mycobacteria (including MAC), Rickettsia species and some parasites (eg Toxoplasma gondii).

Macrolides attain high intracellular concentrations, which are theoretically beneficial for the treatment of infections caused by intracellular bacteria.

Oral formulations of erythromycin have variable absorption and are poorly tolerated because of gastrointestinal adverse effects. Poor adherence is likely because of the 4-times-daily dosing regimen. These factors limit the use of erythromycin in practice. Erythromycin is not recommended for neonates (up to 28 days old) because of the risk of pyloric stenosis.

Administration of the oral formulation of clarithromycin to children may be difficult because the product is often unpalatableElgammal, 2023Matsui, 1997. If possible, consider using an alternative antimicrobial.

Erythromycin and clarithromycin are potent inhibitors of the cytochrome P450 enzyme CYP3A4, so they have many clinically significant drug interactions. Consult an appropriate resource on drug interactions if starting or stopping these drugs in patients taking other drugs.

Azithromycin, erythromycin and clarithromycin can prolong the QT interval. For more information on drugs that prolong the QT interval, see the CredibleMeds website.