ABSTRACT
Erythromycin, the first member of the macrolide class to enter clinical use, was introduced in 1952. Erythromycin remained a mainstay antibiotic for several decades both as an inpatient, infusible agent and as an outpatient, orally administered drug until the introduction of the newer macrolide and azalide agents, clarithromycin, azithromycin, and dirithromycin in the early 1990s and recently the ketolide agent telithromycin in 2004. These antibiotics have activity against each of the major pyogenic pathogens playing etiologic roles in respiratory tract infections: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Moreover, they are potent against atypical respiratory tract pathogens: Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila (Chlamydia) pneumoniae. As such, they comprise a class of agents with focused activity against respiratory pathogens, though azithromycin has been increasingly used for enteric infections caused by Salmonella and Shigella. Importantly, they have little role in the treatment of skin and soft tissue infections for which staphylococci are common causes, or opportunistic gram-negative infections such as Pseudomonas aeruginosa. Hence, these antibiotics are considered excellent focused therapy agents for use against respiratory tract infections. Ketolides are a new class of macrolides and are semisynthetic derivates of erythromycin A. Their defining characteristic is the removal of the neutral sugar, L-cladinose, from the third position of the ring and subsequent oxidation of the 3-hydroxyl to a 3-keto functional group. Telithromycin is the first of this new class of drugs to be approved for clinical use while ABT-733 is a ketolide agent in development. Ketolides are designed to combat respiratory tract pathogens that have acquired resistance to macrolides and have excellent microbiologic activity against drug-resistant S. pneumoniae.
