The in vitro activity of tigecycline was evaluated against baseline pathogens isolated from patients enrolled in phase 3 clinical trials for community-acquired pneumonia conducted in 29 countries worldwide. Tigecycline was active against the most prevalent pathogens, including Streptococcus pneumoniae (MIC(90) 0.06 mg/L), Staphylococcus aureus (MIC(90) 0.25 mg/L), Haemophilus influenzae (MIC(90) 0.5 mg/L) and Klebsiella pneumoniae (MIC(90) 1 mg/L). Twelve isolates of S. pneumoniae expressing tet(M) and two isolates of K. pneumoniae producing extended-spectrum beta-lactamases isolated during the study were susceptible to tigecycline. The excellent in vitro activity of tigecycline against these clinical isolates confirmed its potential utility against pathogens associated with community-acquired pneumonia.