In vitro antibacterial activity of tigecycline against resistant Gram-negative bacilli and enterococci by time–kill assay

This time–kill study was performed with 65 genetically unique clinical isolates of Gram-negative bacilli and enterococci to further define the antibacterial activity of tigecycline. To our knowledge, this is the largest published time–kill study evaluating tigecycline activity to date. Isolates evaluated were 10 meropenem-resistant Acinetobacter baumannii; 15 Escherichia coli, including 10 extended-spectrum β-lactamase (ESBL) producers; 15 Klebsiella pneumoniae, including 10 ESBL producers; 20 vancomycin-resistant Enterococcus faecium (VRE), including 10 that were linezolid resistant; and 5 vancomycin-susceptible Enterococcus faecalis. Time–kill testing was performed using tigecycline concentrations of 1×, 2×, and 4× MIC with colony-forming units (CFU) per milliliter determined at 0, 4, 8, 12, 24, 36, and 48 h. Tigecycline MICs (μg/mL) were ≤1 for E. coli and K. pneumoniae, regardless of the isolates' ESBL production; A. baumannii, 0.06 to 4; 9/10 (90%) were ≤2; E. faecalis ≤0.12; and VRE ≤0.25, regardless of linezolid susceptibility. In the time–kill assay, tigecycline significantly inhibited bacterial growth when compared with the growth control. The reduction in growth was <3 log10 CFU/mL for all isolates, indicative of a bacteriostatic effect.