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The macrolides are a group of closely related compounds characterized by a macrocyclic lactone ring with various sugars attached. Representative antibiotics include erythromycin, azithromycin, clarithromycin, and fidaxomicin.


Erythromycins inhibit protein synthesis by binding to the 50S subunit of bacterial ribosomes. While they are generally bacteriostatic, they can be bactericidal for certain organisms. Similar to penicillin, the rate of macrolide-resistant S pneumoniae is high (25–35%), and increased regional resistance in group A streptococci has been intermittently reported. Erythromycin-resistant pneumococci are resistant to azithromycin and clarithromycin as well. Chlamydia, Mycoplasma, Legionella, and Campylobacter organisms are susceptible to all the macrolides.


Preparations for oral use include erythromycin base, erythromycin stearate, estolate, and ethyl succinate. Erythromycins are excreted primarily nonrenally therefore, no adjustment is required in kidney dysfunction. Azithromycin is available for oral and intravenous use. Clarithromycin is only available as an oral preparation in the United States, but an intravenous preparation is available outside of the United States.


Macrolides are effective in the treatment of infection due to Legionella, Mycoplasma, Ureaplasma, Corynebacterium (including diphtheria), Chlamydia, and Chlamydophila (including ocular and respiratory infections) organisms. They are useful alternatives in the treatment of certain patients with a serious penicillin allergy. When administered early, erythromycin may shorten the course of Campylobacter enteritis. Erythromycins are effective against certain Bartonella species (bacillary angiomatosis) and Rhodococcus species. Clarithromycin, in combination with proton pump inhibitors, is useful in the treatment of Helicobacter pylori. Treatment of atypical mycobacteria infections, particularly Mycobacterium avium complex, whenever possible, should include azithromycin or clarithromycin in combination therapy.

These agents are also sometimes used for their anti-inflammatory action. In vitro data suggest that macrolides have a direct effect on neutrophil function and the production of cytokines associated with inflammation. The most well-documented non-antibacterial benefit associated with the macrolides (azithromycin) is in the prevention of cystic fibrosis exacerbation. Evidence does not support the use of macrolides for prevention or treatment of coronary artery disease.


Nausea, vomiting, and diarrhea may occur after oral or intravenous intake. Erythromycins—particularly the estolate—can produce acute cholestatic hepatitis (fever, jaundice, impaired liver function), probably as a hypersensitivity reaction. Reversible auditory impairment occurs with large prolonged dosing, particularly in patients with impaired kidney or liver function. Clarithromycin and erythromycin have been associated with prolongation of the QT interval and torsades de pointes, more commonly in women. Erythromycins (and clarithromycin) can increase the effects of oral anticoagulants, colchicine, digoxin, theophylline, calcium channel blockers, and cyclosporine by inhibiting cytochrome P450. An increased risk of cardiac-associated death has been reported with clarithromycin and erythromycin, particularly in patients receiving concomitant inhibitors of cytochrome P450 3A4. Considering the substantially improved safety and minimal drug interactions with azithromycin, this agent should be preferentially used over either clarithromycin or erythromycin.

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