Azithromycin is an azilide antimicrobial agent similar to the widely used macrolide antibiotics, such as erythromycin. The acid stability of azithromycin provides highly favorable pharmacokinetic properties and patient tolerance. This azilide compound interferes with bacterial protein synthesis, giving it bactericidal activity against Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae. Reed and Blumer reviewed the pharmacokinetics and spectrum of antibacterial activity of azithromycin, noting that many pathogens responsible for infections in infants and children are within the scope of antibacterial activity of this agent.

Most strains of staphylococci and streptococci, with the exception of enterococci, are susceptible to azithromycin. Concentrations of the drug in tissue and cells are far in excess of concentrations in the blood. The authors report that the primary advance that azithromycin offers in the spectrum of antibacterial activity is against gram-negative pathogens, most notably Haemophilus species. Azithromycin and most newer macrolide antibiotics have demonstrated good to excellent activity against beta-lactamase–positive or beta-lactamase–negative organisms. Azithromycin is also highly active against Chlamydia, Mycoplasma, Bordetella and Borrelia, although azithromycin's activity against Borrelia burgdorferi (Lyme disease) requires further study. Resistance to erythromycin is highly suggestive of resistance to azithromycin.

Pharmacokinetic studies demonstrate better gastrointestinal absorption, greater tissue penetration and a longer elimination half-life with azithromycin than with erythromycin. These characteristics allow once-daily dosing and a shortened duration of therapy, features that distinguish azithromycin from all other orally administered antibiotics used in infants and children.

Most macrolide antibiotics, but not the azilides, seem to have the capacity to interfere with the hepatic metabolism of certain hepatically metabolized drugs, including theophylline, terfenidine and carbamazepine.

Decreased gastrointestinal side effects have been noted with azilides, providing a high degree of patient acceptability. There seems to be no basis for concern about prolonged drug-induced reactions secondary to the longer elimination half-life of azithromycin.

A five-day course of azithromycin has been widely used for the treatment of acute otitis media and streptococcal pharyngitis in children. Therapy is initiated with a loading dose. Recent studies show similar efficacy with a three-day course for otitis media, which may greatly improve compliance. The palatability of the liquid form also enhances acceptability in children.

The authors note that azithromycin appears to have significant advantages over erythromycin, including improved tolerance and less frequent dosing. Although a three-day course of treatment has been shown to be efficacious in otitis media, this short course has not demonstrated such efficacy in the treatment of streptococcal pharyngitis.