Azalides such as azithromycin are a class of macrolide antibiotics that were originally manufactured in response to the poor acid stability exhibited by original macrolides (erythromycin).[1] Following the clinical overuse of macrolides and azalides, ketolides have been developed to combat surfacing macrolide-azalide resistance among streptococci species.[2] Azalides have several advantages over erythromycin such as more potent gram negative antimicrobial activity, acid stability, and side effect tolerability.[3] Although there are few drug interactions with azithromycin, it weakly inhibits the CYP3A4 enzyme.[2]
Azalides feature a nitrogen atom in their 15-membered macrolide ring, resulting in improved pharmacokinetic properties and greater stability when compared to earlier-generation macrolides.[2][3] Replacement of the ketone group in traditional macrolides with a tertiary amine group confers greater acid stability.[3][4] See Beckmann rearrangement.
Azalides bind to the bacterial 50S ribosomal subunit and inhibit polypeptide elongation by hindering peptidyl transfer RNA translocation.[3]
Applicable pharmacokinetic indexes are free azalide AUC24/MIC because of the post antibiotic effect they exhibit, and free azalide concentration/MIC.[3],[5] Due to their large volume of distribution and lipophilic structure, azalides concentrate effectively in tissue.[3]