The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.