Introduction
Methods
Study procedures and participants
Endpoints
Statistical analysis
Cost-effectiveness evaluation
Results
Patients and primary outcome
Total population | Control perioda
| Intervention periodb
| |
---|---|---|---|
n = 1416 |
n = 685 |
n = 731 | |
Total population | |||
Female gender (2/0) | 500 (35.4) | 247 (36.2) | 253 (34.6) |
Age, years | 59 (48–70) | 60 (48–71) | 59 (48–70) |
Medical admission | 1236 (87.3) | 591 (86.4) | 645 (88.1) |
Hospital-acquired infection | 1024 (72.3) | 490 (71.6) | 534 (72.9) |
Type of severe infection | |||
Sepsis | 907 (64) | 442 (64.6) | 465 (63.5) |
Febrile neutropenia | 440 (31.1) | 222 (32.5) | 218 (29.8) |
Suspicion of endocarditis | 69 (4.9) | 21 (3.1) | 48 (6.6) |
Sepsis |
n = 907 |
n = 442 |
n = 465 |
Female gender (2/0) | 297 (32.8) | 146 (33.2) | 151 (32.5) |
Age, years | 63 (51–73) | 63 (51–73) | 62 (51–73) |
Medical admission | 737 (81.3) | 354 (81.0) | 383 (82.4) |
Hospital-acquired infection | 582 (64.2) | 279 (63.1) | 303 (65.2) |
Acquired in ICU | 209 (23.0) | 87 (19.7) | 122 (26.2) |
Respiratory as primary site of infection | 490 (62.7) | 251 (65.9) | 239 (59.8) |
SOFA score (n = 1/5) | 8 (5–11) | 8 (5–11) | 8 (5–11) |
SAPS II (IQR) | 46 (35–61) | 44 (34–58) | 47 (35–63) |
Febrile neutropenia |
n = 440 |
n = 222 |
n = 218 |
Female gender | 179 (40.7) | 93 (41.9) | 86 (39.5) |
Age, years | 54 (41–62) | 53 (41–62) | 54 (42–61) |
Hospital-acquired infection | 390 (88.6) | 197 (88.7) | 193 (88.5) |
Haematologic disease (5/8) | |||
Acute leukaemia | 209 (49) | 108 (49.8) | 101 (48.1) |
Lymphoproliferative disease | 178 (41.7) | 89 (41.0) | 89 (42.4) |
Otherc
| 40 (9.4) | 20 (9.2) | 20 (9.5) |
Treatment phase (14/21) | |||
First induction | 110 (27.2) | 63 (30.3) | 47 (23.9) |
Consolidation | 118 (29.1) | 74 (35.6) | 44 (22.3) |
Re-induction | 177 (43.7) | 71 (34.1) | 106 (53.8) |
Endocarditis |
n = 69 |
n = 21 |
n = 48 |
Female gender | 24 (34.8) | 8 (40.0) | 16 (32.7) |
Age median (IQR) years old | 63 (51–71) | 62.5 (48–67.5) | 63 (53–73) |
Medical admission | 62 (89.9) | 18 (90.0) | 44 (89.8) |
Preexisting valvulopathy | 42 (60.9) | 12 (60.0) | 30 (61.2) |
Total population
n = 1416 | Control period
n = 685 | Intervention period
n = 731 |
P valuea
| OR (95% CI)b
| ARR (95% CI)c
| |
---|---|---|---|---|---|---|
Primary outcome
| ||||||
Microbiologically documented infection | ||||||
Total population (n = 1416, 685/731)d
| 478 (33.8) | 193 (28.2) | 285 (39.0) | <0.001 | – | – |
Severe sepsis (n = 907, 442/465) | 322 (35.5) | 124 (28.1) | 198 (42.6) | <0.001 | 1.89 (1.43–2.50) | 14.5 (8.4–20.7) |
Febrile neutropenia (n = 440, 222/218) | 137 (31.1) | 67 (30.2) | 70 (32.1) | 0.66 | 1.08 (0.71–1.64) | – |
Suspicion of endocarditis (n = 69, 21/48) | 19 (27.5) | 2 (9.5) | 17 (35.4) | 0.04 | 6.22 (0.98–39.6) | 25.9 (7.4–44.4) |
Secondary outcomes
| ||||||
Pathogens identifiede (n = 1416, 685/731) | ||||||
Gram-negative bacillif
| 192 (13.6) | 67 (9.8) | 125 (17.1) | <0.001 | 1.88 (1.36–2.59) | 7.32 (3.8–10.84) |
Gram-positive coccif
| 288 (20.3) | 124 (18.1) | 164 (22.4) | 0.04 | 1.32 (1.01–1.72) | 4.33 (0.16–8.51) |
Fungi (Candida or Aspergillus)f
| 21 (1.5) | 4 (0.6) | 17 (2.3) | 0.007 | 4.12 (1.38–12.36) | 1.74 (0.51–2.97) |
Not included in the molecular test (anaerobes or other bacteria)f
| 28 (2) | 10 (1.5) | 18 (2.5) | 0.18 | 1.69 (0.77–3.70) | – |
Time (h) to result validation | ||||||
Total population (n = 478, 193/285) | 23.6 (14.9–32) | 27.5 (20.8–50.9) | 22.1 (10.8–27.3) | 0.006 | ||
Severe sepsis (n = 322, 124/198) | 23.2 (14.2–29.3) | 27.4 (19.2–57.0) | 21.6 (10.3–26.3) | <0.001 | ||
Febrile neutropenia (n = 137, 67/70) | 28.5 (19.8–41.8) | 31.5 (21–48.3) | 26.8 (19.5–36.2) | 0.97 | ||
Time (h) to result transmission | ||||||
Total population (n = 478, 193/285) | 27.5 (17.3–62) | 48 (26.3–102) | 23.1 (13.2–36.2) | <0.001 | ||
Severe sepsis (n = 322, 124/198) | 26 (16.9–59.4) | 49.5 (23.6–116) | 22.9 (12.5–32) | <0.001 | ||
Febrile neutropenia (n = 137, 67/70) | 38.2 (25.3–67.5) | 54.8 (32.1–71.3) | 30.8 (21–40.9) | 0.15 | ||
Appropriate antimicrobial treatment with regard to the bacteremia (n = 1375, 666/709) | 395 (28.7) | 157 (23.6) | 238 (33.6) | <0.0001 | 1.63 (1.29–2.07) |
Microbiological documentation | Univariate analysisa
| Multivariate analysisa,b
| ||||
---|---|---|---|---|---|---|
No (n = 585) | Yes (n = 322) | OR (95% CI) |
P value | OR (95% CI) |
P value | |
Intervention period (yes/no) | 267 (45.6) | 198 (61.5) | 1.93 (1.46–2.56) | <0.001 | 1.89 (1.36–2.63) | 0.001 |
Age, years (3/1)c
| 63 (51–73) | 62 (50–73) | 1.08 (0.94–1.24) | 0.29 | – | |
Female gender (2/0) | 184 (31.6) | 113 (35.1) | 1.16 (0.87–1.55) | 0.32 | – | |
Medical admission | 476 (81.4) | 261 (81.1) | 1.01 (0.70–1.44) | 0.98 | – | |
Respiratory primary site of infectiond (87/39) | 359 (72.2) | 131 (46.1) | 0.33 (0.23–0.44) | <0.001 | 0.35 (0.25–0.47) | <0.001 |
Hospital acquired infection | 399 (68.2) | 183 (56.8) | 0.61 (0.46–0.82) | <0.001 | 0.55 (0.40–0.76) | <0.001 |
Severity of the sepsis at inclusion | ||||||
SOFA score (n = 5/1)e
| 8 (5–11) | 8 (5–12) | 1.05 (1.01–1.08) | 0.005 | 1.06 (1.02–1.10) | 0.002 |
Glasgow score (n = 43/23)f
| 14 (7–15) | 14 (7–15) | 1.17 (0.88–1.56) | 0.29 | – | |
SAPS (n = 7/6)g
| 45 (34–58) | 49 (36–65) | 1.16 (1.00–1.34) | 0.047 | – | |
Septic shock | 318 (54.4) | 187 (58.1) | 1.16 (0.88–1.53) | 0.30 | – |
Secondary outcomes
Pathogens identified
Microbial pathogen group and species | Control period | Intervention period | Total | |||
---|---|---|---|---|---|---|
Gram-negative bacilli (GNB) | ||||||
Enterobacteria | 66 (29.5) | 116 (32.6) | 182 (31.4) | |||
Citrobacter freundii
| 1 | 0 | 1 | |||
Citrobacter koseri
| 1 | 0 | 1 | |||
Enterobacter
| 11 | 29 | 40 | |||
Escherichia coli
| 31 | 56 | 87 | |||
Klebsiella
| 18 | 28 | 46 | |||
Proteus mirabilis
| 1 | 1 | 2 | |||
Providencia
| 0 | 1 | 1 | |||
Salmonella enterica
| 2 | 0 | 2 | |||
Serratia marcescens
| 1 | 1 | 2 | |||
Pseudomonas and other strict aerobes bacteria | 9 (4.0) | 26 (7.3) | 35 (6.0) | |||
Acinetobacter sp. | 1 | 1 | 2 | |||
Pseudomonas aeruginosa
| 8 | 21 | 29 | |||
Pseudomonas putida
| 0 | 1 | 1 | |||
Stenotrophomonas maltophilia
| 0 | 3 | 3 | |||
Gram-positive cocci (GPC) | ||||||
Staphylococci | 78 (34.8) | 104 (29.2) | 182 (31.4) | |||
Staphylococcus aureus
| 17 | 41 | 58 | |||
Coagulase negative staphylococci | 61 | 63 | 124 | |||
Streptococci and enterococci | 56 (25.0) | 77 (21.6) | 133 (22.9) | |||
Nonhaemolytic streptococci | 24 | 33 | 57 | |||
Haemolytic streptococci | 2 | 1 | 3 | |||
Pneumococci | 15 | 20 | 35 | |||
Enterococcus faecalis
| 7 | 15 | 22 | |||
Enterococcus faecium
| 5 | 8 | 13 | |||
Other enterococci | 3 | 0 | 3 | |||
Strict anaerobic bacteria | 5 (2.2) | 8 (2.2) | 13 (2.25) | |||
Bacteroides fragilis
| 0 | 3 | 3 | |||
Bacteroides merdae
| 1 | 0 | 1 | |||
Bacteroides sp. | 1 | 0 | 1 | |||
Bacteroides thetaiotaomicron
| 1 | 0 | 1 | |||
Bacteroides vulgatus
| 1 | 0 | 1 | |||
Bilophila wadsworthia
| 1 | 1 | 2 | |||
Desulfovibrio sp. | 0 | 1 | 1 | |||
Clostridium clostridioforme
| 0 | 1 | 1 | |||
Clostridium perfringens
| 0 | 1 | 1 | |||
Fusobacterium nucleatum
| 0 | 2 | 2 | |||
Other bacteria | 6 (2.7) | 7 (2.0) | 13 (2.25) | |||
Bacillus sp. | 2 | 0 | 2 | |||
Corynebacterium sp. | 1 | 3 | 4 | |||
Coxiella sp. | 1 | 0 | 1 | |||
Haemophilus influenzae
| 1 | 2 | 3 | |||
Lactobacillus sp. | 1 | 1 | 2 | |||
Neisseria sp. | 0 | 1 | 1 | |||
Fungi | ||||||
Candida
| 4 (1.8) | 16 (4.5) | 20 (3.5) | |||
Candida albicans
| 2 | 8 | 10 | |||
Candida glabrata
| 1 | 2 | 3 | |||
Candida krusei
| 0 | 1 | 1 | |||
Candida parapsilosis
| 0 | 1 | 1 | |||
Candida sp. | 1 | 4 | 5 | |||
Aspergillus fumigatus
| 0 | 2 (0.6) | 2 (0.3) | |||
Total | 224 (100) | 356 (100) | 580 (100) |
Time interval from blood collection to results
Appropriate antimicrobial treatment
Complications and mortality
Economic evaluation
Measured parameters | Control period (n = 560) | Intervention period (n = 555) |
P valuea
| ||
---|---|---|---|---|---|
Mean cost ± SD (€) | Average number per patient ± SD | Mean cost ± SD (€) | Average number per patient ± SD | ||
Total population | |||||
SeptiFast LightCycler test | 8 | 0.02 | 892 ± 207 | 2 ± 0.4 | NA |
Blood cultures | 125 ± 155 | 6 ± 7 | 109 ± 121 | 5 ± 6 | 0.25 |
Other diagnostic procedures | 648 ± 481 | 17 ± 10 | 590 ± 454 | 15 ± 9 | 0.5 |
Anti-infective treatments | 837 ± 2,304 | 4 ± 2 | 868 ± 2,250 | 4 ± 2 | 0.62 |
Length of hospital stay (days) | 17 ± 11 | 17 ± 11 | 0.34 | ||
Total cost per patient | 18,653 ± 15,966 | 18,118 ± 17,775 | 0.75 | ||
Severe sepsis (n patients) | 370 | 336 | |||
SeptiFast LightCycler test | 3 | 0.01 | 904 ± 230 | 2 ± 0.5 | NA |
Blood cultures | 110 ± 149 | 5 ± 7 | 100 ± 113 | 5 ± 5 | 0.32 |
Other diagnostic procedures | 735 ± 538 | 19 ± 10 | 666 ± 473 | 17 ± 9 | 0.17 |
Anti-infective treatments | 635 ± 1,884 | 4 ± 2 | 676 ± 2,175 | 4 ± 2 | 0.79 |
Length of hospital stay (days) | 18 ± 12 | 16 ± 12 | 0.18 | ||
Total cost per patient | 20,995 ± 17,593 | 19,329 ± 16,355 | 0.09 | ||
Febrile neutropenia (n patients) | 176 | 188 | |||
SeptiFast LightCycler test | 22 | 0.12 | 882 ± 165 | 2 ± 0.4 | NA |
Blood cultures | 160 ± 168 | 7 ± 8 | 132 ± 137 | 6 ± 6 | 0.08 |
Other diagnostic procedures | 448 ± 283 | 19 ± 9 | 423 ± 325 | 13 ± 9 | 0.22 |
Anti-infective treatments | 1,228 ± 2,997 | 4 ± 2 | 1,297 ± 2,444 | 4 ± 2 | 0.98 |
Length of hospital stay (days) | 16 ± 9 | 16 ± 9 | 0.72 | ||
Total cost per patient | 14,033 ± 10,844 | 16,230 ± 13,361 | 0.07 |