Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with eryhromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy. Furthermore, it is likely that azithromycin may supersede erythromycin in the treatment of early Lyme disease and become an alternative to therapy with penicillin or tetracycline antibiotics in this condition. Similarly, if the finding of clinical efficacy of azithromycin in a preliminary study of chancroid is sustained in further clinical trials, then the use of azithromycin might supplant the traditional use of a more frequent erythromycin regimen in this condition. Small initial trials have shown azithromycin to be effective at least in the amelioration of Mycobacterium avium infection in AIDS patients. Comparative clinical trials have shown azithromycin to be better tolerated than eryhromycin, principally through fewer gastrointestinal disturbances. Such studies have also shown the tolerability profile of azithromycin to be superior to that of cefaclor, doxycycline or amoxicillin plus probenecid. In conclusion, with its broad spectrum of antimicrobial activity, proven efficacy in a wide range of community-acquired infections, improved tissue pharmacokinetic and tolerability profiles, and suitability for once daily dosing, azithromycin provides a useful alternative to erythromycin and other macrolides with similar activity. In patients with uncomplicated urethritis or cervicitis associated with C. trachomatis, N. gonorrhoeae or U. urealyticum, azithromycin as a single dose regimen offers distinct advantages over current pharmacological options and should therefore be considered as a first-line therapy.
