Macrolides

Macrolides

Background

Macrolides are defined by a large lactone ring, which varies from 12 to 16 carbons, with 1 or more attached sugar chains. Eyrthromycin and clarithromycin have 14 carbons in their lactone rings while azithromycin has 15.

As 50S ribosomal subunit inhibitors, macrolides exert their bacteriostatic effect by inhibiting protein synthesis.

While not extensively studied, macrolide antibiotics with a different number of carbon atoms in their lactone ring are tolerated by most patients. Macrolide antibiotics are also unlikely to cross-react with macrolide immunosuppressants (e.g., tacrolimus, sirolimus).

Clarithyromycin is used as part of combination treatment for H. pylori. Azithromycin is a part of the first-line combination therapy for Mycobacterium avium complex.

  1. GI side effects: Because macrolides are also agonists for the motilin receptor–stimulating gastric and small intestine motility–they can cause nausea, vomiting, diarrhea, and abdmoninal cramping. Accordingly, erythromycin can be used as a treatment for gastroparesis.

  2. Sensorineural ototoxicity (usually transient).

  3. QT interval prolongation.

Skin Testing

Skin testing for macrolide immediate hypersensitivity has not been shown to be reliable.

Oral Challenge

For patients with a history of immediate hypersensitivity reaction to a macrolide, graded azithromycin challenge can be performed, starting with azithromycin 25 mg followed by 1 hour observation then 250 mg followed by 2 hour observation.

For patients with a history of non-severe delayed hypersensitivity reaction to a macrolide, single dose azithromycin 250 mg challenge with 2 hour observation can be performed. Patients should be instructed to report any other delayed symptoms, which may occur up to 24 to 48 hours after the challenge dose.