Azithromycin: An antibiotic with unusual properties

This issue of the journal contains a section on azithromycin, one of the truly new chemical entities among antibacterial agents developed in recent decades. This antibiotic was synthesized many years ago but due to its unusual properties was overlooked for a considerable time. The azalide group of antibiotics is chemically very similar to the macrolides. The antibacterial Spectrum of its first member, azithromycin, is also similar to that of macrolides such as erythromycin, clarithromycin, josamycin and roxithrornycin. However, the activity o f azithromycin against gram-negative aerobes is better than that of macrolides, notably Escherichia coli and Salmonella spp. normally being sensitive to this agent. Azithromycin is also active against mycobacteria, especially Mycobacterium avium intracelhdare, which in view of the kinetics of this agent may become an important feature. The remarkable feature of azithromycin is not its antibacterial spectrum but its pharmacokinetics. Despite fairly rapid absorption and high bioavailiability, azithromycin achieves very low plasma concentrations; the peak concentration following a single oral dose of 50 mg has been reported to be about 0.5 mg/1 and after 24 hours plasma concentrations are virtually undetectable. Nevertheless, this drug has been proposed for single daily dose treatment of infections caused by Organisms with MICs at or even above 1 mg/l. The reason for this seemingly impossible recommendation is that azithromycin accumulates in cells and tissues to give prolonged and very high concentrations in such compartments.