The macrolides.

Erythromycin, which was introduced over 50 years ago, was the first macrolide to be used clinically. "New" macrolides, for the treatment of patients with various infectious diseases, were not clinically introduced until 40 years later. The pharmacokinetic and adverse events profile of erythromycin initially limited its use to an alternative agent for patients with allergy to beta-lactam agents. However, the emergence of atypical and/or new pathogens and the ongoing escalation of acquired antimicrobial resistance has impacted on the empirical and organism directed therapy of infectious diseases. Azithromycin and clarithromycin were developed by enhancing the basic macrolide structure. Some of the basic features associated with these new agents include a pharmacokinetic profiles that allow once or twice daily dosing with a much lower incidence of side effects and a substantially broader spectrum of activity which includes some Gram-negative bacilli, atypical pathogens and new, unconventional or uncommon pathogens. Clinical trial data has supported the use of "new" macrolides in a wide range of clinical indications, however, some specific indications are currently restricted to treatment with either azithromycin or clarithromycin. Macrolide resistance is a class effect and depending on the mechanism will confer either low or high level resistance. While resistance is problematic, it does not always result in clinical failure. The macrolides are a valuable class of antimicrobial agent and play an important role in the management of infectious diseases.