Tigecyclin--the first glycylcycline to undergo clinical development: an overview of in vitro activity compared to tetracycline.

Tetracycline antimicrobials are characterised by a broad-spectrum of antibacterial activity which includes Gram-positive, most Gram-negative, anaerobic and "atypical" (Legionella pneumophila, Chlamydophila pneumoniae and Mycoplasma pneumoniae) species. However, the original clinical utility of the tetracyclines has been compromised as a result of increasing resistance to them among previously susceptible, common pathogens. Research into structure-activity relationships among various tetracycline derivatives resulted in discovery of the 9-t- butylglycylamido tetracyclines, now known as the glycylcyclines, which are not affected by either specific efflux pump or ribosomal protection mechanisms of resistance. Tigecycline, 9-t-butylglycylamido-minocycline, is the first in the glycylcycline class to undergo clinical development. This review of published in vitro data clearly demonstrates the potent activity of tigecycline against a wide range of common hospital and community bacterial pathogens including those having acquired mechanisms of resistance to older congeners (tetracycline, minocycline and doxycycline). Its activity against multiply-resistant Staphylococcus spp, including glycopeptide-intermediate strains (GISA), Streptococcus pneumoniae, Enterococcus spp. (including vancomycin-resistant strains) and some extended-spectrum, beta-lactamase producing isolates of species of the Enterobacteriaceae, is particularly noteworthy.