Antimicrobial activity of tigecycline tested against organisms causing community-acquired respiratory tract infection and nosocomial pneumonia

Emerging antimicrobial resistance among respiratory tract pathogens has created a critical need for development of new antimicrobial agents that are not affected by the commonly occurring genetic resistance mechanisms. Tigecycline, a novel broad-spectrum parenteral glycylcycline, has been shown to be active against many of Gram-positive, Gram-negative, atypical, and anaerobic organisms, including strains highly resistant to commonly prescribed antimicrobials and was recently approved by the US Food and Drug Administration for treating infections of skin and skin structures, and for intra-abdominal infections. In this study, tigecycline spectrum and potency were evaluated against a global collection of pathogens (2000-2004) recovered from community-acquired respiratory infections (7580 strains) or from hospitalized patients with pneumonia (3183 strains). Among community-acquired infections, the ranking pathogens were Haemophilus influenzae (52.9%; 21% ampicillin-resistant), Streptococcus pneumoniae (39.2%; 23.7% penicillin-nonsusceptible), and Moraxella catarrhalis (7.9%). Tigecycline displayed potent activity by inhibiting 100% of the 3 species at clinically achievable concentrations (2, 1, and 0.5 microg/mL, respectively). The 10 most prevalent pathogens producing 94.3% of pneumonias in hospitalized patients were Staphylococcus aureus (48.5% of strains; 49.4% oxacillin-resistant), Pseudomonas aeruginosa (15.6%), Klebsiella spp. (5.6%), S. pneumoniae (4.6%), Acinetobacter spp. (4.5%), Enterobacter spp. (4.0%), Escherichia coli (3.8%), Serratia marcescens (2.5%), Enterococcus spp. (2.3%), Stenotrophomonas maltophilia (1.8%), and beta-hemolytic streptococci (1.1%). At a concentration of 4 microg/mL, tigecycline inhibited >96% of these pathogens (exception, P. aeruginosa). S. aureus was readily inhibited by tigecycline (MIC50 and MIC90, 0.25 and 0.5 microg/mL, respectively) with all strains inhibited at < or =1 microg/mL. Streptococci recovered from hospitalized patients (beta-hemolytic and S. pneumoniae) were also very susceptible to tigecycline with the highest MIC being 0.12 microg/mL. All E. coli (including 13.3% with an extended-spectrum beta-lactamase ESBL] phenotype) were inhibited by < or =1 microg/mL, and all Klebsiella (25.8% ESBL phenotype) and Enterobacter spp. plus 97.0% of Serratia spp. were inhibited by < or =4 microg/mL. Tigecycline was also active against Acinetobacter spp. and S. maltophilia strains (MIC50 and MIC90, 1 and 4 microg/mL, respectively). Further clinical studies should consider the role that tigecycline may play in the therapy for severe respiratory tract infections, both of nosocomial and community origin.