Table 1.
Baseline demographics and clinical characteristics in ASPECT-NP participants with ventilated hospital-acquired bacterial pneumonia (ITT population). Prognostic factors expected to lead to worse clinical outcomes are in bold text
| C/T (N = 99) |
Meropenem (N = 108) |
Total (N = 207) |
|
|---|---|---|---|
| Sex | |||
| Male, n (%) | 74 (74.7) | 72 (66.7) | 146 (70.5) |
| Female, n (%) | 25 (25.3) | 36 (33.3) | 61 (29.5) |
| Age, years | |||
| < 65, n (%) | 52 (52.5) | 47 (43.5) | 99 (47.8) |
| ≥ 65, n (%) | 47 (47.5) | 61 (56.5) | 108 (52.2) |
| Mean (standard deviation) | 63.3 (15.0) | 65.3 (14.7) | 64.3 (14.9) |
| Median (range) | 64.0 (18, 98) | 66.5 (24, 92) | 65.0 (18, 98) |
| Weight, kg | |||
| Median (range) | 78.1 (34.0, 140.0) | 75.0 (40.0, 151.0) | 78.0 (34.0, 151.0) |
| Body-mass index, kg | |||
| Median (range) | 26.2 (15.1, 44.1) | 26.1 (15.5, 49.3) | 26.1 (15.1, 49.3) |
| Creatinine clearance (mL/min) | |||
| ≥ 150 (augmented renal clearance), n (%) | 9 (9.1) | 5 (4.6) | 14 (6.8) |
| ≥ 80, n (%) | 44 (44.4) | 48 (44.4) | 92 (44.4) |
| < 80 to > 50, n (%) | 26 (26.3) | 34 (31.5) | 60 (29.0) |
| ≤ 50 to ≥ 30, n (%) | 17 (17.2) | 10 (9.3) | 27 (13.0) |
| < 30 to ≥ 15, n (%) | 12 (12.1) | 13 (12.0) | 25 (12.1) |
| < 15 (end-stage renal disease), n (%) | 0 | 0 | 0 |
| Missing, n (%) | 0 | 3 (2.8) | 3 (1.4) |
| In the ICU | |||
| Yes, n (%) | 83 (83.8) | 86 (79.6) | 169 (81.6) |
| No, n (%) | 16 (16.2) | 22 (20.4) | 38 (18.4) |
| APACHE II score | |||
| ≤ 14, n (%) | 32 (32.3) | 27 (25.0) | 59 (28.5) |
| 15–19, n (%) | 36 (36.4) | 40 (37.0) | 76 (36.7) |
| ≥ 20, n (%) | 31 (31.3) | 40 (37.0) | 71 (34.3) |
| Missing, n (%) | 0 | 1 (0.9) | 1 (0.5) |
| Mean (standard deviation) | 17.5 (6.1) | 18.4 (5.9) | 18.0 (6.0) |
| Median (range) | 16.0 (4, 33) | 17.0 (5, 38) | 17.0 (4, 38) |
| SOFA score | |||
| ≤ 7, n (%) | 57 (57.6) | 65 (60.2) | 122 (58.9) |
| > 7, n (%) | 42 (42.4) | 41 (38.0) | 83 (40.1) |
| Missing, n (%) | 0 | 2 (1.9) | 2 (1.0) |
| Mean (standard deviation) | 7.2 (2.7) | 7.1 (2.7) | 7.1 (2.7) |
| Median (range) | 7 (0, 13) | 7 (1, 15) | 7 (0, 15) |
| Prior non-study gram-negative therapy* | |||
| Yes, n (%) | 92 (92.9) | 93 (86.1) | 185 (89.4) |
| No, n (%) | 7 (7.1) | 15 (13.9) | 22 (10.6) |
| Failed prior antibacterial therapy for NP | |||
| Yes, n (%) | 20 (20.2) | 17 (15.7) | 37 (17.9) |
| No, n (%) | 79 (79.8) | 90 (83.3) | 169 (81.6) |
| Missing, n (%) | 0 | 1 (0.9) | 1 (0.5) |
| Adjunctive gram-negative therapy§ | |||
| Yes, n (%) | 35 (35.4) | 34 (31.5) | 69 (33.3) |
| No, n (%) | 64 (64.6) | 70 (64.8) | 134 (64.7) |
| Missing, n (%) | 0 | 4 (3.7) | 4 (1.9) |
| CPIS | |||
| ≤ 6, n (%) | 9 (9.1) | 7 (6.5) | 16 (7.7) |
| 7, n (%) | 12 (12.1) | 7 (6.5) | 19 (9.2) |
| 8, n (%) | 13 (13.1) | 13 (12.0) | 26 (12.6) |
| > 8, n (%) | 65 (65.7) | 80 (74.1) | 145 (70.0) |
| Missing, n (%) | 0 | 1 (0.9) | 1 (0.5) |
| Duration of prior hospitalization† | |||
| < 5 days, n (%) | 27 (27.3) | 32 (29.6) | 59 (28.5) |
| ≥ 5 days, n (%) | 71 (71.7) | 72 (66.7) | 143 (69.1) |
| Missing, n (%) | 1 (1.0) | 4 (3.7) | 5 (2.4) |
| Mean (standard deviation), days | 9.8 (7.7) | 9.8 (13.4) | 9.8 (11.0) |
| Median (range), days | 8.0 (1, 42) | 6.0 (1, 116) | 7.0 (1, 116) |
| Duration of prior mechanical ventilation† | |||
| < 5 days, n (%) | 88 (88.9) | 93 (86.1) | 181 (87.4) |
| ≥ 5 days, n (%)‡ | 11 (11.1) | 12 (11.1) | 23 (11.1) |
| Missing, n (%) | 0 | 3 (2.8) | 3 (1.4) |
| Mean (standard deviation), days | 2.20 (3.08) | 3.13 (8.30) | 2.68 (6.33) |
| Median (range), days | 1.18 (0.02, 20.06) | 1.14 (0.04, 79.04) | 1.14 (0.04, 79.04) |
| PaO2/FiO2 | |||
| ≤ 240 mmHg, n (%) | 75 (75.8) | 79 (73.1) | 154 (74.4) |
| > 240 mmHg, n (%) | 23 (23.2) | 27 (25.0) | 50 (24.2) |
| Missing, n (%) | 1 (1.0) | 2 (1.9) | 3 (1.4) |
| Bacteremia (any pathogen) | |||
| Yes, n (%) | 14 (14.1) | 11 (10.2) | 25 (12.1) |
| No, n (%) | 85 (85.9) | 97 (89.8) | 182 (87.9) |
| Number of baseline LRT pathogens | |||
| None confirmed, n (%) | 24 (24.2) | 24 (22.2) | 48 (23.2) |
| Monomicrobial, n (%) | 42 (42.4) | 45 (41.7) | 87 (42.0) |
| Polymicrobial, n (%) | 33 (33.3) | 39 (36.1) | 72 (34.8) |
APACHE, Acute Physiology and Chronic Health Evaluation. CPIS, Clinical Pulmonary Infection Score. C/T, ceftolozane/tazobactam. ICU, intensive care unit. ITT, intent-to-treat. NP, nosocomial pneumonia. SOFA, Sequential Organ Failure Assessment
*Antibacterial therapy active against gram-negative pathogens received in the 72 h prior to first dose of study drug
§Defined as adjunctive empirical therapy with amikacin, which was protocol permitted for up to 72 h at study sites where ≥ 15% of P aeruginosa isolates were resistant to meropenem according to the site’s most recent antibiogram
†Assessed as prior to randomization
‡Since some of these patients may have failed prior antibacterial therapy for ventilated NP, and because the denominator includes patients with vHABP, this number is not an exact substitute for late VABP