TABLE 2.
PK-PD breakpoints for amoxicillin in serum and cortical and cancellous bone for 30-min infusions of 2,000 mg amoxicillin and 200 mg clavulanic acid q4h, q6h, or q8h at steady state
| Target fT>MIC (%) | Dosing interval (h) | PK-PD breakpoint concna
|
||
|---|---|---|---|---|
| Serum (mg/liter) | Cortical bone (μg/g) | Cancellous bone (μg/g) | ||
| 30 | 4 | 24 | 6 | 4 |
| 30 | 6 | 16 | 3 | 2 |
| 30 | 8 | 8 | 2 | 1.5 |
| 50 | 4 | 12 | 3 | 2 |
| 50 | 6 | 6 | 1.5 | 1 |
| 50 | 8 | 3 | 0.75 | 0.5 |
| 70 | 4 | 2.0 | 1.5 | |
| 70 | 6 | 0.5 | 0.5 | |
| 70 | 8 | 0.25 | 0.1875 | |
| 100 | 4 | 0.75 | 0.5 | |
| 100 | 6 | 0.1875 | 0.125 | |
| 100 | 8 | 0.03125 | 0.03125 | |
a
The breakpoints are based on the estimates from NONMEM (Table 1). A level of protein binding of 18% in both serum and bone was assumed.