ABSTRACT
The ketolides are a new class of antibacterial agents derived from the 14membered macrolactone ring that characterizes the macrolides. Novel structural modifications result in enhanced binding to bacterial ribosomes through tighter binding at domain V of bacterial rRNA relative to erythromycin A and direct binding at a second site in domain II of bacterial rRNA. The result of this improved ribosomal binding is increased potency against respiratory tract pathogens, including macrolide-resistant strains. Ketolides do not induce expression of macrolide-lincosamide-streptograminB (MLSB) resistance. They have an optimum spectrum of activity for the treatment of respiratory tract infections (RTIs), being highly active against common, atypical, and intracellular respiratory pathogens such as Streptococcus pneumoniae (including penicillin-, macrolide-, and azalide-resistant strains),Haemophilus influenzae and Moraxella catarrhalis (including h-lactamase-producing strains), Staphylococcus aureus, Streptococcus pyogenes (including many macrolide-and azalide-resistant strains), respiratory anaerobes, Legionella
pneumophila, Chlamydophila pneumoniae, and Mycoplasma pneumoniae. Ketolides also possess good activity against Coxiella burnetii, Francisella tularensis, Corynebacterium diphtheriae, Bordetella pertussis, and Bordetella parapertussis. The ketolides display concentration-dependent bactericidal activity. They achieve high concentrations in plasma, respiratory tissues, alveolar macrophages, and neutrophils. Their targeted spectrum of antibacterial activity and favorable pharmacokinetic/pharmacodynamic (PK/PD) profile make this class of agents ideal for the treatment of lower and upper RTIs, including community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), acute maxillary sinusitis (AMS), and tonsillitis/pharyngitis. Telithromycin-the first ketolide antibacterial to be approved for clinical use-has been both effective and well tolerated in over 1 million patients since its commercial introduction. Telithromycin retains clinical efficacy in the therapy of patients with resistant pathogens, and has been efficacious even in the setting of bacteremic pneumococcal disease caused by penicillin-and macrolide-resistant strains. Side effects, when they do occur, are mild and consistent in incidence and severity with other approved antibacterial agents, particularly the macrolides. Drug-drug interactions are few and are similar to those of the macrolides.
