Article Figures & Data
Figures
- FIG. 1.
Antibacterial effect of simulated human free-drug serum concentration-time profiles of telavancin, vancomycin, and teicoplanin against MSSA strain 38002 (a), MRSA strain 36895 (b), and VISA strain 19898 (c). The error bars indicate standard deviations.
- FIG. 2.
Antibacterial effect of simulated human free-drug serum concentration-time profiles of telavancin, vancomycin, and teicoplanin against E. faecalis strain 37976 (a), E. faecium strain 37780 (b), and vancomycin-resistant E. faecium strain 31040 (c). The error bars indicate standard deviations.
- FIG. 3.
Telavancin fAUC/MIC relationship AUBKC24 for vancomycin-susceptible S. aureus (a) and Enterococcus spp. (b).
Tables
- TABLE 1.
Telavancin, vancomycin, and teicoplanin MICs for S. aureus and the Enterococcus spp. used
Strain type Strain no. MIC (mg/liter) Telavancin Vancomycin Teicoplanin MRSA 22706 0.25 1.5 0.12 MRSA 33024 0.19 0.19 0.25 MRSA 36895 0.19 2.0 0.19 MSSA 38002 0.38 1.5 0.25 MRSA 38601 0.19 1.0 0.19 VISA 19898 0.75 8 16 VISA 24764 1.0 VISA 25949 1.0 VISA 26089 0.75 E. faecalis 37976 0.25 0.75 0.12 E. faecium 37780 0.12 0.25 0.12 E. faecium (VR) 31040 1.5 128 1.5 - TABLE 2.
Pharmacokinetic parameters for telavancin, vancomycin, and teicoplanin
Parametera Value Telavancin Vancomycin Teicoplanin Cmax (mg/liter) 11.1 ± 2.5 13.9 ± 0.2 3.6 ± 0.9 AUC0-24 (mg/liter·h) 95.7 ± 3.3 193.4 ± 16.2 43.6 ± 11.2 t1/2 (h) 7.4 ± 0.3 5.0 ± 0.4 14.0 ± 6.0 C at 12 h (mg/liter) 2.1 ± 0.5 4.4 ± 1.0 1.6 ± 0.6 C at 24 h (mg/liter) <1 <1 ↵a C, concentration.
- TABLE 3.
Comparative antibacterial effects of free-drug serum concentrations of simulations of telavancin, teicoplanin, and vancomycin against pooled data from 4 MRSA strains
ABE measure Value Telavancin Teicoplanin Vancomycin No. of simulations 18 12 17 Log change in viable count (log CFU/ml) at (h): 6 −3.5 ± 0.6a −2.0 ± 0.4 −2.5 ± 0.7 12 −3.5 ± 0.5a −2.7 ± 0.2 −3.0 ± 0.7 24 −3.0 ± 0.8 −2.8 ± 0.5 −2.8 ± 0.8 36 −3.0 ± 0.7 −2.7 ± 0.8 −2.7 ± 0.9 48 −2.8 ± 0.8 −2.1 ± 1.4 −2.8 ± 1.0 Maximum reduction in viable count (log CFU/ml) −4.0 ± 0.5a −3.2 ± 0.5 −3.3 ± 0.6 AUBKC24 (log CFU/ml·h) 21.7 ± 7.7a 42.0 ± 5.3 36.9 ± 13.7 AUBKC48 (log CFU/ml·h) 43.8 ± 20.0a 76.3 ± 21.1 65.9 ± 29.4 ↵a Telavancin was superior to vancomycin and teicoplanin (P < 0.05).
- TABLE 4.
Relationship between telavancin free-drug AUC/MIC ratio and antibacterial effect at 24 h for vancomycin-susceptible S. aureus, vancomycin-intermediate S. aureus, and Enterococcus spp.
Strain Telavancin MIC (μg/ml) fAUC/MIC ratio Static effect −1-log-unit reduction in viable count −2-log-unit reduction in viable count MRSA 33024 0.19 95.0 98.4 105.5 36895 0.19 67.7 80.4 95.5 38601 0.19 37.8 43.3 27706 0.25 11.8 23.5 49.6 38002 0.38 3.1 4.4 15.8 Mean ± SD 43.1 ± 38.4 50.0 ± 39.0 55.1 ± 37.2 VISA 19898 0.75 2.1 3.1 4.7 26089 0.75 4.8 6.1 7.4 24764 1.0 2.3 3.6 5.9 25949 1.0 3.7 4.7 6.0 Mean ± SD 3.2 ± 1.3 4.3 ± 1.3 6.0 ± 1.1 E. faecium 37780 0.12 17.0 60.2 E. faecalis 37976 0.25 5.6 6.3 VR E. faecium 31040 1.5 22.9 53.7 170 Mean ± SD 15.1 ± 8.8 40.1 ± 29.4 - TABLE 5.
Relationship between telavancin free-drug AUC/MIC ratio and risk of emergence of resistance in vancomycin-susceptible S. aureus and Enterococcus sp. strains as assessed by organism growth on 2× MIC recovery media
fAUC/MIC ratio S. aureus Enterococcus spp. No. of expt % with growth on 2× MIC recovery media (n) Viable count (log CFU/ml) on 2× MIC recovery plates No. of expt % with growth on 2× MIC recovery media (n) Viable count (log CFU/ml) on 2× MIC recovery plates <1 0 3 0 <2 ≥1-3 8 100 (8) 5.6 ± 1.9 7 29 (2) 3.6 >3-10 3 100 (3) 4.7 ± 0.6 5 60 (3) 3.1 ± 0.9 >10-50 8 50 (4) 4.3 ± 1.1 6 17 (1) 4.4 >50-175 7 29 (2) 4.2 3 0 <2 >175-400 7 14 (1) 2.1 4 0 <2 >400 5 0 <2 5 0 <2
