Telithromycin: The First Ketolide

infections (RTIs) continues to be an international challenge; RTIs are associated with considerable morbidity and mortality in both developed and developing countries. Globally, lower RTIs accounted for 4.3 million premature deaths in 1990.1 A major barrier to the confident prescribing of empiric therapies for RTIs is the increasing resistance worldwide among respiratory tract pathogens to existing antimicrobial agents.2,3 Although the clinical impact of penicillin-resistant Streptococcus pneumoniae (S. pneumoniae) has been controversial in non-meningococcal respiratory infections, the usefulness of penicillin against this pathogen can be reduced by the progressive development of resistance.2-6 Even more worrisome is the fact that penicillin-resistant S. pneumoniae strains are often resistant to other ß-lactams and the macrolides.7-10 The macrolide-linosamide-streptogramin (MLSB) group of antimicrobials are clinically valuable drugs, particularly for the treatment of RTIs, which can be caused by S. pneumoniae as well as by “atypical” pathogens like Mycoplasma pneumoniae. Resistance of S. pneumoniae to these antimicrobials, however, is increasing on an international scale. From 1997 to 1998, non-susceptible rates ranged from 9% in the United Kingdom to 74% in China. Of most recent concern is the emergence, noted in some studies, of occasional resistance to fluoroquinolones. Resistance is associated with the increased use of these agents.11-13 Telithromycin (Ketek, Aventis) is the first of a new family of semisynthetic antimicrobials known as the ketolides. Chemically derived from the macrolides, this novel antibiotic has been specifically developed to overcome the problem of increasing resistance to the antimicrobials in the MLSB group, and is characterized by a broad microbiological spectrum, a unique mechanisms of action, and a favorable resistance profile. Most importantly, it possesses good in vitro activity against most of the common respiratory pathogens, including S. pneumoniae that are resistant to beta-lactams or macrolides. If, however, the strains resistant to macrolides carry the ermB gene, many of those strains will also be resistant to telithromycin.14,15