Macrolides: A Canadian Infectious Disease Society position paper

Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.Key Words: Azithromycin, Clarithromycin, Erythromycin, Macrolides, Review, Therapeutic useErythromycin A is a naturally occurring, microbiologically active compound of the macrolide class of antibiotics. Chemical modification of erythromycin A''s 14-membered lactone ring has led to the formation of semisynthetic derivatives with not only improved bioavailability and tolerability, but also expanded spectrums of microbiological activity and improved pharmacokinetic profiles. Such modifications produced clarithromycin, classified as a macrolide because it retains the central 14-membered lactone ring (1,2), and azithromycin, classified as an azalide due to its 15-membered aglycone ring (1). The latter two compounds are the newest agents in the macrolide class licensed for use in Canada. Roxithromycin and dirithromycin are available in other countries.These compounds are clinically active against Gram-positive and Gram-negative cocci, and Gram-negative bacilli (primarily Haemophilus influenzae, Legionella species, Moraxella catarrhalis, Campylobacter jejuni, Bordatella pertussis and Helicobacter pylori). Azalides such as azithromycin have exhibited superior activity against Gram-negative pathogens and are generally less active against Gram-positive pathogens. Intracellular pathogens such as Chlamydia species, Mycoplasma species, Ureaplasma species, Borrelia species and nontuberculous mycobacteria species show varying susceptibilities. On the basis of their microbial activity, both the macrolides and azalides have been shown to be clinically useful in the treatment of uncomplicated skin and soft tissue infections, upper and lower respiratory tract infections, sexually transmitted Chlamydia trachomatis infection and peptic ulcer disease. Additionally, the improved pharmacokinetic profiles and acid stability exhibited by the newer agents may lead to enhanced patient adherence through less frequent dosing and improved bioavailability in the presence of food.