Background
Methods
Definition of patient population and trial selection
Trial search and data collection
Patients and endpoints
Statistical analysis
Results
Results of the search and characteristics of included trials
First author (year) | Country | Setting, type of trial | Patients included | Follow-up | Clinical diagnosis | Type of procalcitonin algorithm; procalcitonin cutoffs used (μg/L)a | Compliance with the PCT protocol |
---|---|---|---|---|---|---|---|
Annane (2013) [7] | France | ICU, multicenter | 62 | Hospital stay | Severe sepsis without overt source of infection and negative blood culture | Initiation and duration; R against AB: < 0.5 (< 0.25); R for AB: > 0.5 (> 5.0) | 63% adherence |
Bloos (2016) [8] | Germany | ICU, multicenter | 1089 | 3 months | Severe sepsis or septic shock (SIRS and documented infection + criteria for severe sepsis/septic shock) | Discontinuation at days 4, 7, and 10; R against AB: < 1.0 or > 50% drop over previous value | 49.6% adherence |
Bouadma (2010) [9] | France | ICU, multicenter | 621 | 2 months | Critically ill patients with assumed/proven bacterial infection | Initiation and duration; R against AB: < 0.5 (< 0.25); R for AB: > 0.5 (> 1.0) | 47% adherence |
De Jong (2016) [10] | The Netherlands | ICU, multicenter | 1546 | 1 year | Critically ill patients with assumed infection | Duration; R against AB: < 0.5 or > 80% drop over peak value | 44% adherence |
Deliberato (2013) [11] | Brazil | ICU, single center | 81 | ICU discharge or 14 days postrandomization | Sepsis patients with microbiologically confirmed bacterial infection | Duration; R against AB: < 0.5 or > 90% drop over peak value | 47.6% adherence |
Hochreiter (2009) [14] | Germany | Surgical ICU, single center | 110 | Hospital stay | Sepsis (SIRS and documented infection) | Duration; R against AB: < 1 or > 65% drop over 3 days | not reported |
Layios (2012) [15] | Belgium | ICU, single center | 379 | 1 month | Critically ill patients with assumed infection | Initiation; R against AB: < 0.5 (< 0.25); R for AB: > 0.5 (> 1.0) | 46.3% adherence |
Nobre (2008) [17] | Switzerland | ICU, single center | 79 | 1 month | Severe sepsis or septic shock | Duration; R against AB: < 0.5 (< 0.25) or > 80% drop over peak value; R for AB: > 0.5 (> 1.0) | 81% adherence |
Oliveira (2013) [16] | Brazil | ICU, multicenter | 94 | 28 days or hospital discharge | Severe sepsis or septic shock (SOFA score > 10 and/or bacteremia) | Discontinuation; Initial < 1.0: R against AB: 0.1 at day 4; Initial > 1.0: R against: > 90% drop over peak value | 87.8% adherence |
Schroeder (2009) [13] | Germany | Surgical ICU, single center | 27 | Hospital stay | Severe sepsis following abdominal surgery (SIRS and documented infection + criteria for severe sepsis/septic shock) | Duration; R against AB: < 1 or > 65% drop over 3 days | not reported |
Shehabi (2014) [1] | Australia | ICU, multicenter | 394 | 3 months | Sepsis (SIRS and documented infection) | Duration; R against AB: < 0.25 (< 0.1) or > 90% drop over peak value | 97% adherence |
Parameter | Control group (n = 2230) | PCT group (n = 2252) |
---|---|---|
Demographics | ||
Age (years) | 64.1 ± 15.0 | 63.5 ± 15.2 |
Male gender | 1281 (57.5%) | 1273 (56.5%) |
Primary focus of infection | ||
Respiratory | 1101 (49.4%) | 1102 (48.9%) |
Urinary | 129 (5.8%) | 118 (5.2%) |
Abdominal | 417 (18.7%) | 391 (17.4%) |
Skin/soft tissue | 41 (1.8%) | 32 (1.4%) |
CNS | 35 (1.6%) | 38 (1.7%) |
Other/unknown | 440 (19.7%) | 519 (23.0%) |
Genital/gynecologic | 8 (0.4%) | 3 (0.1%) |
Catheter-related | 14 (0.6%) | 16 (0.7%) |
Bloodstream | 36 (1.6%) | 25 (1.1%) |
Upper respiratory | 9 (0.4%) | 8 (0.4%) |
Vital signs | ||
Temperature (°C) | 37.7 ± 1.2 | 37.8 ± 1.1 |
Sepsis score | ||
Meeting sepsis 3 definition | 1630 (73.1%) | 1605 (71.3%) |
SOFA score (points) | 7.4 ± 4.0 | 7.3 ± 4.1 |
Additional sepsis support | ||
Vasopressor use | 1593 (76.3%) | 1606 (76.7%) |
Ventilation support | 1434 (68.1%) | 1478 (69.4%) |
Renal replacement | 767 (34.4%) | 757 (33.6%) |
Primary safety endpoint: mortality
Control group | PCT group | Adjusted OR or difference (95% CI)a, p value | p value for interaction | |
---|---|---|---|---|
2230 | 2252 | |||
Overall | ||||
Antibiotic therapy (days) | 10.4 ± 9.7 | 9.3 ± 9.2 | −1.19 (−1.73 to −0.66), p < 0.001 | |
30-day mortality | 529 (23.7%) | 475 (21.1%) | 0.89 (0.8 to 0.99), p = 0.03 | |
Length of hospital stay (days) | 28.7 ± 27.9 | 28.6 ± 27.9 | 0.09 (−1.51 to 1.7), p = 0.908 | |
Length of ICU stay (days) | 14.7 ± 16.3 | 14.8 ± 16.5 | 0.04 (−0.9 to 0.99), p = 0.928 | |
Subgroup by sepsis definition | ||||
Meeting sepsis 3 definition | 1630 | 1605 | ||
Antibiotic therapy (days) | 10.5 ± 9.2 | 9.3 ± 8.9 | −1.22 (−1.82 to −0.62), p < 0.001 | 0.915 |
30-day mortality | 397 (24.4%) | 338 (21.1%) | 0.86 (0.76 to 0.98), p = 0.022 | 0.388 |
Length of hospital stay (days) | 29.5 ± 27.9 | 29.6 ± 29.4 | 0.07 (−1.89 to 2.03), p = 0.946 | 0.891 |
Length of ICU stay (days) | 14.1 ± 15.5 | 14.5 ± 17.0 | 0.37 (−0.74 to 1.48), p = 0.51 | 0.246 |
Not meeting sepsis 3 definition | 600 | 647 | ||
Antibiotic therapy (days) | 10.2 ± 10.9 | 9.1 ± 9.9 | −1.13 (−2.27 to 0.01), p = 0.052 | 0.915 |
30-day mortality | 132 (22.0%) | 137 (21.2%) | 0.96 (0.78 to 1.19), p = 0.717 | 0.388 |
Length of hospital stay (days) | 26.4 ± 27.9 | 26.2 ± 23.7 | 0.16 (−2.53 to 2.84), p = 0.909 | 0.891 |
Length of ICU stay (days) | 16.5 ± 18.3 | 15.6 ± 15.2 | −0.82 (−2.65 to 1.01), p = 0.378 | 0.246 |
Subgroup by organ failure | ||||
SOFA 0 to 6 | 763 | 776 | ||
Antibiotic therapy (days) | 10.9 ± 10.3 | 8.1 ± 8.2 | −2.62 (−3.51 to −1.73), p < 0.001 | < 0.001 |
30-day mortality | 105 (13.8%) | 91 (11.7%) | 0.85 (0.66 to 1.1), p = 0.227 | 0.991 |
Length of hospital stay (days) | 28.6 ± 28.6 | 26.8 ± 25.8 | −1.96 (−4.65 to 0.72), p = 0.152 | 0.138 |
Length of ICU stay (days) | 12.9 ± 16.7 | 12.1 ± 15.6 | −0.92 (−2.52 to 0.69), p = 0.263 | 0.083 |
SOFA 7 to 9 | 474 | 445 | ||
Antibiotic therapy (days) | 10.1 ± 8.2 | 10.2 ± 9.4 | 0.01 (−1.1 to 1.11), p = 0.988 | 0.003 |
30-day mortality | 112 (23.6%) | 96 (21.6%) | 0.92 (0.73 to 1.17), p = 0.512 | 0.601 |
Length of hospital stay (days) | 30.7 ± 26.4 | 29.4 ± 25.9 | −1.14 (−4.52 to 2.24), p = 0.508 | 0.543 |
Length of ICU stay (days) | 14.0 ± 14.3 | 14.1 ± 15.3 | 0.23 (−1.66 to 2.12), p = 0.813 | 0.862 |
SOFA 10 to 24 | 486 | 486 | ||
Antibiotic therapy (days) | 10.7 ± 9.1 | 10.0 ± 8.8 | −0.63 (−1.71 to 0.45), p = 0.256 | 0.125 |
30-day mortality | 190 (39.1%) | 161 (33.1%) | 0.86 (0.72 to 1.01), p = 0.065 | 0.576 |
Length of hospital stay (days) | 29.4 ± 27.5 | 32.6 ± 35.5 | 3.21 (−0.76 to 7.18), p = 0.113 | 0.024 |
Length of ICU stay (days) | 15.6 ± 15.4 | 17.7 ± 19.2 | 2.08 (−0.08 to 4.24), p = 0.059 | 0.036 |
No septic shock (no vasopressor use) | 495 | 489 | ||
Antibiotic therapy (days) | 11.2 ± 9.9 | 9.8 ± 9.2 | −1.35 (−2.53 to −0.17), p = 0.025 | 0.586 |
30-day mortality | 79 (16.0%) | 76 (15.5%) | 0.97 (0.73 to 1.28), p = 0.823 | 0.512 |
Length of hospital stay (days) | 24.9 ± 26.3 | 23.2 ± 20.6 | −1.49 (−4.35 to 1.38), p = 0.309 | 0.258 |
Length of ICU stay (days) | 13.2 ± 15.6 | 12.7 ± 14.2 | −0.43 (−2.25 to 1.39), p = 0.642 | 0.47 |
Septic shock (with vasopressor use) | 1593 | 1606 | ||
Antibiotic therapy (days) | 10.4 ± 9.8 | 9.3 ± 9.4 | −1.03 (−1.68 to −0.39), p = 0.002 | 0.586 |
30-day mortality | 420 (26.4%) | 376 (23.4%) | 0.89 (0.79 to 1), p = 0.051 | 0.512 |
Length of hospital stay (days) | 30.1 ± 27.0 | 30.6 ± 26.3 | 0.6 (−1.23 to 2.43), p = 0.52 | 0.258 |
Length of ICU stay (days) | 15.0 ± 16.1 | 15.4 ± 17.0 | 0.34 (−0.8 to 1.49), p = 0.557 | 0.47 |
No respiratory failure (invasive ventilation support) | 672 | 651 | ||
Antibiotic therapy (days) | 11.0 ± 11.4 | 9.5 ± 9.6 | −1.43 (−2.49 to − 0.37), p = 0.008 | 0.467 |
30-day mortality | 104 (15.5%) | 83 (12.7%) | 0.83 (0.64 to 1.08), p = 0.158 | 0.633 |
Length of hospital stay (days) | 25.4 ± 21.7 | 25.3 ± 23.3 | −0.01 (−2.33 to 2.31), p = 0.993 | 0.788 |
Length of ICU stay (days) | 11.7 ± 13.5 | 12.4 ± 14.2 | 0.53 (− 0.86 to 1.92), p = 0.456 | 0.433 |
Respiratory failure (invasive ventilation support) | 1434 | 1478 | ||
Antibiotic therapy (days) | 10.2 ± 9.0 | 9.2 ± 9.2 | −1.09 (−1.73 to −0.45), p = 0.001 | 0.467 |
30-day mortality | 401 (28.0%) | 373 (25.2%) | 0.89 (0.79 to 1), p = 0.058 | 0.633 |
Length of hospital stay (days) | 30.9 ± 30.9 | 30.3 ± 26.0 | −0.39 (−2.42 to 1.65), p = 0.708 | 0.788 |
Length of ICU stay (days) | 16.2 ± 17.5 | 16.0 ± 17.5 | −0.3 (−1.56 to 0.95), p = 0.637 | 0.433 |
No renal replacement therapy | 1463 | 1495 | ||
Antibiotic therapy (days) | 9.4 ± 9.2 | 8.4 ± 8.6 | −1.02 (−1.64 to −0.39), p = 0.001 | 0.475 |
30-day mortality | 301 (20.6%) | 265 (17.7%) | 0.86 (0.74 to 1), p = 0.046 | 0.553 |
Length of hospital stay (days) | 29.8 ± 31.1 | 28.4 ± 25.5 | −1.41 (−3.4 to 0.59), p = 0.168 | 0.026 |
Length of ICU stay (days) | 14.6 ± 17.4 | 14.1 ± 15.9 | −0.64 (−1.82 to 0.53), p = 0.284 | 0.077 |
Renal replacement therapy | 767 | 757 | ||
Antibiotic therapy (days) | 12.3 ± 10.2 | 10.9 ± 10.0 | −1.45 (−2.44 to −0.46), p = 0.004 | 0.475 |
30-day mortality | 228 (29.7%) | 210 (27.7%) | 0.96 (0.83 to 1.11), p = 0.584 | 0.553 |
Length of hospital stay (days) | 26.6 ± 20.5 | 29.1 ± 32.2 | 2.97 (0.31 to 5.63), p = 0.028 | 0.026 |
Length of ICU stay (days) | 14.9 ± 14.0 | 16.2 ± 17.5 | 1.43 (−0.16 to 3.02), p = 0.079 | 0.077 |
Control group | PCT group | Adjusted OR or difference (95% CI)a, p value | p value for interaction | |
---|---|---|---|---|
Subgroup by type of infection (suspected infection site) | ||||
Respiratory | 1101 | 1102 | ||
Antibiotic therapy (days) | 9.9 ± 7.8 | 8.5 ± 7.8 | −1.36 (−1.99 to −0.73), p < 0.001 | 0.582 |
30-day mortality | 262 (23.8%) | 243 (22.1%) | 0.92 (0.79 to 1.07), p = 0.299 | 0.466 |
Length of hospital stay (days) | 28.2 ± 27.7 | 27.7 ± 24.7 | −0.21 (−2.36 to 1.94), p = 0.849 | 0.668 |
Length of ICU stay (days) | 15.1 ± 16.6 | 15.3 ± 17.5 | 0.19 (−1.24 to 1.61), p = 0.798 | 0.858 |
Urinary | 129 | 118 | ||
Antibiotic therapy (days) | 12.5 ± 12.4 | 11.0 ± 12.2 | −1.62 (−4.6 to 1.36), p = 0.286 | 0.786 |
30-day mortality | 21 (16.3%) | 11 (9.3%) | 0.59 (0.3 to 1.16), p = 0.128 | 0.215 |
Length of hospital stay (days) | 29.5 ± 25.4 | 25.1 ± 21.7 | −4.08 (−9.7 to 1.54), p = 0.154 | 0.209 |
Length of ICU stay (days) | 14.3 ± 20.5 | 11.2 ± 13.6 | −2.49 (−6.68 to 1.7), p = 0.244 | 0.123 |
Abdominal | 417 | 391 | ||
Antibiotic therapy (days) | 10.5 ± 10.6 | 11.0 ± 11.9 | 0.55 (−0.96 to 2.06), p = 0.477 | 0.005 |
30-day mortality | 109 (26.1%) | 89 (22.8%) | 0.87 (0.68 to 1.11), p = 0.266 | 0.821 |
Length of hospital stay (days) | 30.5 ± 27.7 | 32.1 ± 27.8 | 1.62 (−2.18 to 5.41), p = 0.404 | 0.361 |
Length of ICU stay (days) | 15.1 ± 15.3 | 15.7 ± 16.4 | 0.42 (−1.76 to 2.6), p = 0.704 | 0.634 |
Skin/soft tissue | 41 | 32 | ||
Antibiotic therapy (days) | 12.9 ± 15.8 | 8.6 ± 8.5 | −4.57 (−10.36 to 1.23), p = 0.122 | 0.159 |
30-day mortality | 11 (27%) | 8 (25%) | 0.94 (0.43 to 2.06), p = 0.874 | 0.918 |
Length of hospital stay (days) | 26.0 ± 25.8 | 20.9 ± 23.4 | −4.17 (−15.4 to 7.06), p = 0.467 | 0.442 |
Length of ICU stay (days) | 10.4 ± 9.4 | 10.9 ± 12.7 | 0.83 (−4.18 to 5.84), p = 0.747 | 0.916 |
Central nervous system | 35 | 38 | ||
Antibiotic therapy (days) | 11.7 ± 7.7 | 10.4 ± 7.7 | −1.7 (−5.04 to 1.63), p = 0.317 | 0.958 |
30-day mortality | 3 (9%) | 2 (5%) | 0.61 (0.11 to 3.46), p = 0.58 | 0.692 |
Length of hospital stay (days) | 31.3 ± 22.8 | 30.8 ± 25.7 | −0.44 (−11.48 to 10.6), p = 0.938 | 0.954 |
Length of ICU stay (days) | 10.8 ± 14.0 | 13.7 ± 13.1 | 2.91 (−3.22 to 9.04), p = 0.352 | 0.457 |