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

Abstract

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 resistance in the community, which tends to parallel the (often inappropriate) overuse of such agents. Such problems highlight the need for new antibacterial agents that retain activity against bacterial strains resistant to existing agents, and have a low potential to select for resistance or induce cross-resistance. Telithromycin is the first of a new family of antibacterials--the ketolides--and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). Numerous in vitro studies 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 example, MICs were < or = 1 mg/L irrespective of penicillin susceptibility, with > or = 98% of macrolide-resistant strains inhibited at < or = 0.5 mg/L, regardless of the underlying mechanism of resistance (including erm, mef and ribosomal L4 mutations). Against Haemophilus influenzae and Moraxella catarrhalis, including beta-lactamase-positive strains, telithromycin is at least as potent as azithromycin. In addition, telithromycin has a very low potential for selection of resistant isolates or induction of cross-resistance. Importantly, and unlike existing macrolides, telithromycin does not induce MLS(B) resistance, a finding explained by the presence of the innovative 3-keto group in its chemical structure. Telithromycin therefore represents an important addition to the therapeutic armamentarium in an era of increasing antimicrobial resistance, with an expected low likelihood of the development of resistance in clinical use.