TABLE 4.
Parameter | n | Ceftazidime |
Avibactam |
Joint PK/PD target attainment rate, % (95% CI)b | ||
---|---|---|---|---|---|---|
Cmax,ss (mg/liter) | AUCss,0–24 (mg ⋅ h/liter) | Cmax,ss (mg/liter) | AUCss,0–24 (mg ⋅ h/liter) | |||
Indication | ||||||
cIAI | 703 | 66.9 (105.0) | 749 (114.0) | 12.8 (155.3) | 132 (152.0) | 98.6 (97.7–99.5) |
cUTI | 648 | 77.9 (114.2) | 979 (119.7) | 12.1 (161.9) | 138 (164.1) | 98.5 (97.5–99.4) |
NP | 413 | 72.9 (125.2) | 950 (131.0) | 14.2 (166.1) | 169 (168.5) | 99.0 (98.1–100.0) |
Non-VAP | 275 | 79.0 (120.0) | 1,016 (122.0) | 15.5 (166.9) | 183 (168.7) | 99.6 (98.9–100.0) |
VAP | 138 | 61.9 (127.0) | 830 (142.7) | 12 (157.6) | 146 (163.0) | 97.8 (95.4–100.0) |
Age (yr) | ||||||
18–65 | 1,192 | 70.0 (113.5) | 800 (122.7) | 12.5 (167.1) | 131 (166.8) | 98.4 (97.7–99.1) |
>65–75 | 284 | 77.1 (109.4) | 997 (107.6) | 13.2 (119.0) | 156 (118.4) | 99.6 (99.0–100.0) |
>75–89 | 288 | 76.8 (120.5) | 1,102 (120.6) | 14.0 (169.6) | 180 (164.7) | 98.6 (97.3–100.0) |
BMI (kg/m2) | ||||||
<29.9 | 1,441 | 73.0 (115.5) | 878 (124.2) | 13.0 (160.2) | 144 (161.4) | 98.7 (98.1–99.3) |
≥29.9–<34.9 | 208 | 67.9 (111.8) | 841 (125.2) | 12.0 (178.4) | 136 (179.1) | 97.6 (95.5–99.7) |
≥34.9–<39.9 | 74 | 73.7 (109.6) | 894 (115.2) | 13.2 (139.7) | 141 (140.0) | 100.0 (NA) |
≥39.9 | 32 | 64.2 (93.6) | 806 (119.4) | 9.7 (116.9) | 115 (128.5) | 100.0 (NA) |
Missing | 9 | 70.9 (87.0) | 959 (106.5) | 14.2 (83.4) | 172 (112.8) | 100.0 (NA) |
Day 3 CLCR (ml/min)d | ||||||
8–15 | 4 | 34.3 (173.3) | 551 (121.9) | 6.3 (305.6) | 86.3 (220.6) | 75.0 (32.6–100.0) |
>15–30 | 20 | 50.4 (139.5) | 789 (116.5) | 10.9 (174.1) | 155 (143.6) | 100.0 (NA) |
>30–50 | 128 | 58.8 (120.5) | 938 (122.9) | 10.2 (147.6) | 148 (153.3) | 98.4 (96.3–100.0) |
>50–80 | 418 | 90.0 (108.0) | 1,213 (110.4) | 15.3 (142.9) | 186 (144.5) | 99.0 (98.1–100.0) |
>80–150 | 955 | 72.9 (105.9) | 828 (112.4) | 13.2 (165.5) | 138 (163.4) | 99.0 (98.3–99.6) |
>150–180 | 123 | 58.5 (93.0) | 652 (112.8) | 9.9 (124.5) | 103 (137.5) | 98.4 (96.1–100.0) |
>180–610 | 116 | 51.2 (109.6) | 542 (108.1) | 9.9 (171.6) | 96 (155.9) | 95.7 (92.0–99.4) |
Bacteraemia at baseline | ||||||
No | 1,465 | 71.9 (116.1) | 881 (125.5) | 12.6 (157.3) | 141 (161.2) | 98.6 (98.0–99.2) |
Yes | 88 | 73.6 (102.8) | 919 (120.1) | 14.2 (164.1) | 161 (161.3) | 100.0 (NA) |
Baseline APACHE II score | ||||||
≤10 | 677 | 67.0 (105.0) | 748 (113.8) | 12.7 (154.3) | 131 (150.6) | 98.5 (97.6–99.4) |
>10 | 438 | 72.3 (124.3) | 938 (130.9) | 14.3 (167.0) | 170 (168.7) | 99.1 (98.2–100.0) |
Missingc | 649 | 77.9 (114.1) | 979 (119.7) | 12.1 (161.8) | 138 (164.0) | 98.5 (97.5–99.4) |
SIRS at baseline | ||||||
No | 770 | 72.3 (108.9) | 895 (120.5) | 12.8 (159.2) | 143 (162.0) | 99.1 (98.4–99.8) |
Yes | 773 | 71.5 (121.3) | 869 (129.7) | 12.6 (157.1) | 142 (161.3) | 98.3 (97.4–99.2) |
Missing | 10 | 83.5 (130.2) | 977 (123.7) | 12.1 (115.1) | 129 (116.4) | 100.0 (NA) |
Baseline WBC count (cells/μl) | ||||||
≤12,000 | 876 | 74.6 (110.9) | 923 (118.9) | 12.8 (159.1) | 145 (161.7) | 98.9 (98.2–99.6) |
>12,000 | 486 | 67.6 (119.4) | 801 (128.4) | 12.5 (160.4) | 136 (161.5) | 98.6 (97.5–99.6) |
Missing | 191 | 72.0 (121.4) | 924 (136.8) | 12.3 (145.3) | 147 (158.6) | 98.4 (96.7–100.0) |
Fever at baseline | ||||||
No | 1,166 | 71.9 (113.4) | 888 (123.9) | 12.9 (154.5) | 146 (159.2) | 99.1 (98.5–99.6) |
Yes | 343 | 72.1 (121.8) | 859 (130.3) | 12.2 (165.7) | 134 (167.4) | 98.3 (96.9–99.6) |
Missing | 44 | 75.1 (117.3) | 929 (118.4) | 11.8 (180.9) | 132 (164.7) | 93.2 (85.7–100.0) |
Table adapted from Li et al. (16). APACHE, Acute Physiology and Chronic Health Evaluation; AUCss,0–24; area under the curve over 24 h at steady state; BMI, body mass index; CI, confidence interval; cIAI, complicated intra-abdominal infection; Cmax,ss, maximum concentration at steady state; CLCR, creatinine clearance; cUTI, complicated urinary tract infection; NP, nosocomial pneumonia; q8h, every 8 h; q24 h, every 24 h; PD, pharmacodynamic; PK, pharmacokinetic; SIRS, systemic inflammatory response syndrome; WBC, white blood cell; NA, not applicable.
The joint PK/PD target was defined as 50% fT>MIC of 8 mg/liter for ceftazidime and 50% fT>CT of 1 mg/liter for avibactam.
APACHE II scores were collected for cIAI and NP patients only, hence these data were not available for the 648 cUTI patients. Data were missing for one cIAI patient.
Patients with CLCR <50 ml/min were assumed to receive the labeled dosage regimen appropriate to their level of renal insufficiency.