In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and Gram-positive cutaneous infections

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC90, 0.5 mug/mL) and coagulase-negative staphylococci (1,432 strains; MIC90, 0.5 mug/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC90, less than or equal to0.25 mug/mL), viridans group streptococci (212 strains; MIC90, less than or equal to0.25-0.5 mug/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC90, 0.25-0.5 mug/mL), beta-haemolytic streptococci (405 strains; MIC90, less than or equal to0.25 mug/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC90, 1 mug/mL), Moraxella catarrhalis (495 strains; MIC90, 0.25 mug/mL), and Neisseria meningitidis (17 strains; MIC90, less than or equal to0.12 mug/mL) were inhibited by 2 mug/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC90 of 0.5 mug/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections. (C) 2004 Elsevier Inc. All rights reserved.