Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin

Antimicrobial resistance amongst common respiratory pathogens has increased worldwide at an alarming rate and now threatens the clinical usefulness of a number of antibacterial agents. A major concern is the selection of resi stance in the community, which tends to parallel the (often inappropriate) overuse of such agents. Such problems highlight the need for new antibacter ial agents that retain activity against bacterial strains resistant to exis ting agents, and have a low potential to select for resistance or induce cr oss-resistance. Telithromycin is the first of a new family of antibacterial s-the ketolides-and has been designed specifically for the treatment of com munity-acquired respiratory tract infections (RTIs). Numerous in vitro stud ies confirm the potent activity of telithromycin against pathogens commonly implicated in community-acquired RTIs, irrespective of their beta -lactam, macrolide or fluoroquinolone susceptibility. Against pneumococci, for exam ple, MICs were less than or equal to1 mg/L irrespective of penicillin susce ptibility, with greater than or equal to 98% of macrolide-resistant strains inhibited at less than or equal to0.5 mg/L, regardless of the underlying m echanism of resistance (including erm, mef and ribosomal L4 mutations). Aga inst Haemophilus influenzae and Moraxella catarrhalis, including beta -lact amase-positive strains, telithromycin is at least as potent as azithromycin . In addition, telithromycin has a very low potential for selection of resi stant isolates or induction of cross-resistance. Importantly, and unlike ex isting macrolides, telithromycin does not induce MLSB resistance, a finding explained by the presence of the innovative 3-keto group in its chemical s tructure. Telithromycin therefore represents an important addition to the t herapeutic armamentarium in an era of increasing antimicrobial resistance, with an expected low likelihood of the development of resistance in clinica l use.