TABLE 1.
| ClCr (mL/min) | Infusion time | Dosing frequency | Values for drug: |
PTA |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ceftolozane |
Tazobactam |
Ceftolozane (MIC = 4 mg/L; fT>MIC ≥ 32.2%) | Tazobactam (CT = 0.25 mg/L; fT>CT ≥ 35%) | |||||||
| Cmax (mg/L) | Cmin (mg/L) | AUC0–24h (mg.h/L) | Cmax (mg/L) | Cmin (mg/L) | AUC0–24h (mg.h/L) | |||||
| 100 | 1 h | q12h | 48.0 (26.1–96.2) | 2.2 (0.2–12.3) | 348.0 (184.1–657.6) | 14.9 (7.2–30.2) | 0.0 (0.0–1.9) | 62.8 (23.9–165.4) | 98.0 | 85.7 |
| 100 | 2 h | q12h | 40.4 (22.8–71.0) | 2.5 (0.2–13.2) | 348.0 (184.1–657.5) | 10.7 (5.2–21.3) | 0.0 (0.0–2.0) | 62.8 (23.9–165.3) | 99.1 | 91.9 |
| 100 | 4 h | q12h | 30.4 (18.1–50.7) | 3.3 (0.3–15.0) | 347.8 (184.1–657.1) | 6.8 (2.9–14.6) | 0.1 (0.0–2.4) | 62.8 (23.9–165.3) | 100 | 100 |
| 100 | 6 h | q12h | 24.1 (14.1–40.0) | 4.4 (0.6–16.6) | 347.8 (184.1–656.9) | 4.9 (2.0–11.5) | 0.2 (0.0–2.9) | 62.8 (23.9–165.2) | 100 | 100 |
| 100 | 12 h | q12h | 14.4 (7.2–27.2) | 14.4 (7.2–27.2) | 344.7 (172.8–651.5) | 2.6 (0.9–6.8) | 2.6 (0.9–6.8) | 62.0 (21.7–163.1) | 100 | 100 |
| 51 | 1 h | q12h | 56.5 (32.0–110.2) | 7.5 (0.9–26.5) | 563.2 (298.0–1,064.3) | 17.8 (8.4–36.5) | 0.2 (0.0–4.5) | 98.7 (37.5–259.7) | 100 | 97.4 |
| 51 | 2 h | q12h | 50.7 (29.5–89.3) | 8.1 (1.1–27.3) | 563.2 (298.0–1,064.2) | 13.7 (6.9–26.4) | 0.3 (0.0–4.7) | 98.7 (37.5–259.6) | 100 | 98.5 |
| 51 | 4 h | q12h | 41.5 (24.8–70.5) | 9.7 (1.5–29.5) | 562.8 (297.9–1,063.6) | 9.6 (4.3–19.3) | 0.5 (0.0–5.2) | 98.6 (37.5–259.5) | 100 | 100 |
| 51 | 6 h | q12h | 34.9 (20.5–59.1) | 11.6 (2.3–31.9) | 562.8 (297.9–1,063.2) | 7.3 (3.0–16.4) | 0.7 (0.0–5.8) | 98.6 (37.5–259.4) | 100 | 100 |
| 51 | 12 h | q12h | 23.2 (11.6–43.9) | 23.2 (11.6–43.9) | 558.0 (279.7–1,054.4) | 4.1 (1.4–10.7) | 4.1 (1.4–10.7) | 97.3 (34.1–256.1) | 100 | 100 |
| 50 | 1 h | q12h | 56.8 (32.2–110.7) | 7.8 (1.0–27.1) | 571.4 (302.3–1,079.5) | 17.9 (8.5–36.6) | 0.3 (0.0–4.6) | 100.0 (38.0–263.2) | 100 | 97.4 |
| 50 | 2 h | q12h | 51.1 (29.6–89.8) | 8.4 (1.2–27.8) | 571.2 (302.2–1,079.3) | 13.8 (6.9–26.6) | 0.3 (0.0–4.8) | 100.0 (38.0–263.1) | 100 | 98.5 |
| 50 | 4 h | q12h | 41.9 (25.0–71.1) | 9.9 (1.6–30.1) | 570.8 (302.1–1,078.8) | 7.3 (2.0–17.1) | 0.5 (0.0–5.3) | 100.0 (38.0–263.0) | 100 | 100 |
| 50 | 6 h | q12h | 35.2 (20.8–59.8) | 11.9 (2.4–32.4) | 570.8 (302.1–1,078.4) | 7.3 (3.1–16.5) | 0.7 (0.0–5.9) | 100.0 (38.0–262.9) | 100 | 100 |
| 50 | 12 h | q12h | 23.6 (11.8–44.6) | 23.6 (11.8–44.6) | 565.8 (283.7–1,069.4) | 4.1 (1.4–10.8) | 4.1 (1.4–10.8) | 98.6 (34.5–259.5) | 100 | 100 |
| 30 | 1 h | q12h | 67.1 (38.3–125.2) | 15.8 (3.0–44.4) | 823.2 (435.6–1,555.2) | 20.0 (9.7–41.0) | 0.8 (0.0–7.7) | 140.8 (53.5–370.6) | 100 | 99.6 |
| 30 | 2 h | q12h | 62.2 (36.0–108.3) | 16.8 (3.4–45.8) | 823.2 (435.6–1,555.0) | 16.3 (8.3–31.5) | 1.0 (0.0–8.0) | 140.8 (53.5–370.5) | 100 | 99.9 |
| 30 | 4 h | q12h | 53.3 (31.8–90.3) | 18.9 (4.5–47.9) | 822.6 (435.3–1,554.4) | 12.1 (5.8–24.3) | 1.3 (0.0–9.0) | 140.8 (53.5–370.3) | 100 | 100 |
| 30 | 6 h | q12h | 46.7 (27.4–81.3) | 21.4 (5.8–50.1) | 822.4 (435.2–1,554.0) | 9.7 (4.2–22.0) | 1.8 (0.1–10.0) | 140.7 (53.5–370.2) | 100 | 100 |
| 30 | 12 h | q12h | 34.0 (17.0–64.2) | 34.0 (17.0–64.2) | 815.4 (408.8–1,540.9) | 5.8 (2.0–15.2) | 5.8 (2.0–15.2) | 138.9 (48.6–365.5) | 100 | 100 |
| 29 | 1 h | q24h | 55.1 (30.9–109.6) | 3.3 (0.2–16.1) | 414.3 (214.0–779.9) | 19.1 (8.4–39.5) | 0.0 (0.0–2.2) | 70.1 (25.7–183.5) | 99.5 | 88.5 |
| 29 | 2 h | q24h | 50.3 (29.2–89.6) | 3.5 (0.2–16.5) | 414.3 (214.0–779.8) | 15.5 (7.4–30.0) | 0.0 (0.0–2.3) | 70.1 (25.7–183.5) | 99.8 | 90.8 |
| 29 | 4 h | q24h | 40.8 (25.0–68.3) | 3.9 (0.3–17.3) | 414.0 (213.9–779.5) | 11.2 (5.5–21.7) | 0.1 (0.0–2.6) | 70.0 (25.7–183.4) | 99.9 | 95.6 |
| 29 | 12 h | q24h | 27.1 (15.9–45.5) | 6.6 (0.9–21.5) | 413.7 (213.8–778.8) | 5.4 (2.1–12.4) | 0.2 (0.0–3.8) | 70.0 (25.7–183.2) | 100 | 100 |
| 29 | 24 h | q24h | 17.0 (9.0–30.3) | 17.0 (9.0–30.3) | 407.1 (220.3–728.0) | 2.8 (1.1–6.9) | 2.8 (1.1–6.9) | 68.3 (26.9–165.3) | 100 | 100 |
| 15 | 1 h | q24h | 63.4 (37.1–119.8) | 10.2 (1.4–33.2) | 664.0 (343.0–1,248.4) | 21.0 (9.3–43.7) | 0.3 (0.0–5.6) | 109.0 (39.9–285.3) | 100 | 98.3 |
| 15 | 2 h | q24h | 59.6 (35.3–106.4) | 10.7 (1.5–33.9) | 663.9 (343.0–1,248.3) | 18.0 (8.7–35.2) | 0.3 (0.0–5.7) | 109.0 (39.9–285.3) | 100 | 98.7 |
| 15 | 4 h | q24h | 53.5 (32.1–90.6) | 11.6 (1.8–35.3) | 663.5 (342.8–1,248.0) | 14.2 (7.1–27.1) | 0.4 (0.0–6.1) | 109.0 (39.9–285.2) | 100 | 99.3 |
| 15 | 12 h | q24h | 39.0 (22.5–66.5) | 15.9 (3.7–40.2) | 662.8 (342.6–1,247.2) | 7.9 (3.2–17.5) | 0.9 (0.0–7.5) | 108.9 (39.9–284.9) | 100 | 100 |
| 15 | 24 h | q24h | 27.2 (14.4–48.6) | 27.2 (14.4–48.6) | 652.3 (353.0–1,166.1) | 4.4 (1.7–10.7) | 4.4 (1.7–10.7) | 106.2 (41.8–257.1) | 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). Dose for all regimens is 1,000/500 mg.
b
Abbreviations: AUC0–24h, area under the concentration-time curve 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.