Table 1.
Free (non-serum-protein-bound) pharmacokinetic-pharmacodynamic values generated with the fractionated NXL104 regimensa
| Regimen | Free time-above MIC (mg/liter) | Free Cmax (mg · h/liter) | Free 24-h AUC (h/%) |
|---|---|---|---|
| Ceftaroline, 600 mg, q8h | 22.3 | 266 | 0/0 |
| Ceftaroline in combination with NXL104 (free 24-h AUC of 192 mg · h/liter) administered as: | |||
| Total daily dose q24h | 46.5 | 192 | 9.6/40 |
| One-half the total daily dose q12h | 24.0 | 192 | 14.8/62 |
| One-third the total daily dose q8h | 17.7 | 192 | 19.2/80 |
| Continuous infusion | 8.0 | 192 | 24.0/100 |
a
For K. pneumoniae 27-908M, the MIC for ceftaroline monotherapy was 1,048 mg/liter. The MICs of ceftaroline in combination with NXL104 were 0.75 mg/liter for CPT and 4 mg/liter for NXL104 (all NXL104 concentrations were fixed at 4 mg/liter). For the combination therapies, time ≥ MICs were calculated for the duration (hours and percentage of 24 h) in which the concentration of ceftaroline was ≥0.75 mg/liter and the concentration of NXL104 was ≥4 mg/liter.