Skip to main content
. 2019 Mar 27;63(4):e02187-18. doi: 10.1128/AAC.02187-18

TABLE 4.

Individual ceftazidime and avibactam steady-state exposures (geometric mean [CV%]) and joint PK/PD target attainment at an MIC of 8 mg/liter for ceftazidime and avibactam for subgroups of actual phase 3 patientsa

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)
a

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.

b

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.

c

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.

d

Patients with CLCR <50 ml/min were assumed to receive the labeled dosage regimen appropriate to their level of renal insufficiency.