Variation in Potency and Spectrum of Tigecycline Activity against Bacterial Strains from US Medical Centers since Its Approval for Clinical Use (2006 to 2012)

Tigecycline was initially approved by the U.S. Food and Drug Administration (FDA) in June 2005. We assessed the evolution of tigecycline in vitro activities since the initial approval of tigecycline for clinical use by analyzing the results of 7 years (2006 to 2012) of data from the SENTRY Antimicrobial Surveillance Program in the United States. We also analyzed trends over time for key resistance phenotypes. The analyses included 68,608 unique clinical isolates collected from 29 medical centers and tested for susceptibility using reference broth microdilution methods. Tigecycline was highly active against Gram-positive organisms, with MIC50 and MIC90 values of 0.12 and 0.25 mu g/ml for Staphylococcus aureus (28,278 strains; >99.9% susceptible), 0.06 to 0.12 and 0.12 to 0.25 mu g/ml for enterococci (99.3 to 99.6% susceptible), and <= 0.03 and <= 0.03 to 0.06 mu g/ml for streptococci (99.9 to 100.0% susceptible), respectively. When tested against 20,457 Enterobacteriaceae strains, tigecycline MIC50 and MIC90 values were 0.25 and 1 mu g/ml, respectively (98.3% susceptible using U. S. FDA breakpoints). No trend toward increasing tigecycline resistance (nonsusceptibility) was observed for any species or group during the study period. The prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae increased from 4.4 and 0.5%, in 2006 to 8.5 and 1.5% in 2012, respectively. During the same period, the prevalence of Escherichia coli and Klebsiella spp. with an extended-spectrum beta-lactamase (ESBL) phenotype increased from 5.8 and 9.1% to 11.1 and 20.4%, respectively, whereas rates of meropenem-non-susceptible Klebsiella pneumoniae escalated from 2.2% in 2006 to 10.8% in 2012. The results of this investigation show that tigecycline generally retained potent activities against clinically important organisms isolated in U.S. institutions, including MDR organism subsets of Gram-positive and Gram-negative pathogens.