TABLE 4.
| ClCr (ml/min) | Dose (mg) | Infusion time | Dosing frequency | Value for drug: |
PTA |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Ceftazidime |
Avibactam |
||||||||||
| Cmax (mg/L) | Cmin (mg/L) | AUC0–24h (mg.h/L) | Cmax (mg/L) | Cmin (mg/L) | AUC0–24h (mg.h/L) | Ceftolozane (MIC = 4 mg/L; fT>MIC ≥ 32.2%) | Tazobactam (CT = 0.25 mg/L; fT>CT ≥ 35%) | ||||
| 80 | 2,000/500 | 2h | q8h | 71.9 (31.8–169.1) | 12.5 (3.9–62.8) | 914.9 (403.7–2,023.7) | 11.2 (3.3–39.2) | 0.6 (0.1–5.2) | 106.5 (34.0–322.7) | 99.4 | 97.4 |
| 51 | 2,000/500 | 2h | q8h | 95.3 (41.7–226.9)a | 29.9 (11.5–107.3) | 1,435.2 (633.2–3,165.5)a | 14.8 (4.4–53.0)a | 1.9 (0.5–11.1) | 170.8 (54.5–517.6) | 100 | 100 |
| 50 | 1,000/250 | 2h | q8h | 48.2 (21.1–115.3) | 15.4 (6.0–55.0) | 731.0 (322.9–1,613.9) | 7.5 (2.2–26.9) | 1.0 (0.3–5.8) | 87.2 (27.8–264.2) | 99.6 | 96.9 |
| 31 | 1,000/250 | 2h | q8h | 67.7 (29.4–153.8) | 32.2 (14.0–93.2) | 1,178.7 (520.8–2,550.9) | 10.2 (3.0–36.5) | 2.8 (0.9–11.7) | 144.1 (46.0–436.4) | 100 | 99.9 |
| 30 | 750/187.5 | 2h | q12h | 40.5 (16.6–101.0) | 13.2 (4.9–44.3) | 601.1 (257.6–1,317.2) | 6.5 (1.7–25.8) | 0.9 (0.3–5.4) | 73.1 (22.4–222.6) | 99.1 | 93.4 |
| 16 | 750/187.5 | 2h | q12h | 62.2 (26.1–140.3) | 34.0 (14.0–85.4) | 1,124.6 (483.0–2,435.0) | 9.6 (2.7–36.1) | 3.2 (1.0–12.2) | 141.3 (43.3–428.5) | 100 | 99.8 |
| 15 | 750/187.5 | 2h | q24h | 42.7 (18.2–106.5) | 12.6 (4.6–44.2) | 606.3 (267.8–1,387.5) | 7.6 (2.0–30.8) | 0.8 (0.2–5.7) | 76.9 (24.4–266.4) | 98.6 | 92.8 |
| 6 | 750/187.5 | 2h | q24h | 76.2 (32.8–173.1) | 45.8 (20.1–108.8)d | 1,426.7 (655.8–2,978.2) | 12.4 (3.5–45.0) | 5.2 (1.7–18.6)d | 197.6 (62.7–655.0)a | 100 | 100 |
a
Concentrations and AUC0–24h at steady state were obtained from simulations on 1,000 virtual patients and are given as median (2.5 to 97.5 percentiles).
b
Abbreviations: AUC0–24h, area under the concentration-time curve up over 24 h; ClCr, creatinine clearance; Cmax, maximal concentration at the end of infusion; Cmin, concentration at steady state or plateau concentration in case of continuous infusion; q12h and q24h, administration every 12 h and 24 h, respectively; PTA, probability of target attainment.
c
Highest median Cmax and AUC0–24h for recommended dosages.
d
Highest median Cmin for recommended dosages.