TABLE 2.
Comparison of different daptomycin regimens for a daptomycin-susceptible, dose-dependent Enterococcus faecium infective endocarditis rat model
| Time from inoculation to treatment (h) | Dose (mg/kg), route | Bacterial load of vegetation (log10 CFUc/g) | Rate of sterile vegetation | Bacterial load in blood (log10 CFUc/mL) |
Cmaxd (mg/L) |
AUC0–24e (mg × h/L) |
No. of rats survivingj/no. treated |
|---|---|---|---|---|---|---|---|
| 24 | 12, i.v.a | 0 (0) | 100 | 0 (0) | 106.2 (56.2) | 228.2 (15.7) | 3/6 |
| 24 | 45, s.c.b | 0 (0) | 100 | 0 (0) | 122.6 (17.1) | 986.7 (185.6) | 3/4 |
| 24 | 90, s.c.b | 0 (0) | 100 | 0 (0) | 178.5 (19.7) | 2,053.6 (352.3) | 3/4 |
| 24 | Control | 7.91 (1.26)f | 0 | 3.67 (0.90) | 3/4 | ||
| 48 | 12, i.v.a | 3.27 (0.11) | 0 | 0 (0) | 106.2 (56.2) | 228.2 (15.7) | 3/7 |
| 48 | 45, s.c.b | 4.75 (0.42)g | 0 | 0 (0) | 122.6 (17.1) | 986.7 (185.6) | 3/6 |
| 48 | 90, s.c.b | 0 (0)h,i | 100 | 0 (0) | 178.5 (19.7) | 2,053.6 (352.3) | 3/5 |
| 48 | Control | 9.00 (1.22) | 0 | 5.02 (5.19) | 3/6 |
a
i.v., intravenously.
b
s.c., subcutaneously.
c
CFU, colony forming units.
d
Cmax, maximum serum concentration.
e
AUC0–24, area under the concentration-time curve from 0 to 24 h.
f
P = 0.34, compared between 24 and 48 h from inoculation to treatment.
g
P = 0.005, compared between 45 mg/kg and the control group.
h
P < 0.001, compared between 90 mg/kg and the control group.
i
P < 0.001, compared between 90 and 45 mg/kg subcutaneously.
j
Survived the entire therapy.