Introduction
Material and methods
Inclusion and exclusion criteria
Definitions
Data collection
Variables
Quality of the database
Ethical issues
Statistical analyses
Results
Patients
Parameters | Total (n = 956) | Died within 60 days (n = 259, 27%)* | Alive on day 60 (n = 697, 73%) | P- value |
---|---|---|---|---|
Variables at admission
| ||||
Male, n (%) | 633 (66.2) | 190 (73.4) | 443 (63.6) | 0.004 |
Age, years (median [IQR]) | 62 [46; 76] | 72 [58; 80] | 58 [42; 73] | <0.0001 |
Scores, median [IQR]
| ||||
SAPSII | 43.5 [31; 59] | 60 [43; 74] | 39 [27; 53] | <0.0001 |
SOFA score | 6 [4; 9] | 9 [6; 12] | 5 [3; 8] | <0.0001 |
LOD score | 5 [2; 7] | 7 [4; 10] | 4 [2; 6] | <0.0001 |
Coma Glasgow Scale | 13 [5; 15] | 7 [3; 15] | 14 [7; 15] | <0.0001 |
McCabe, n (%)
| <0.0001 | |||
1 | 684 (71.7) | 140 (54.1) | 544 (78.3) | |
2 | 235 (24.6) | 98 (37.8) | 137 (19.7) | |
3 | 35 (3.7) | 21 (8.1) | 14 (2.0) | |
CURB-65, n (%)
| <0.0001 | |||
0 | 13 (1.4) | 0 (0) | 13 (1.9) | |
1 | 62 (6.5) | 4(1.6) | 58 (8.3) | |
2 | 176 (18.4) | 22 (8.5) | 154 (22.1) | |
3 | 292 (30.6) | 65 (25.2) | 227 (32.6) | |
4 | 252 (26.4) | 90 (34.9) | 162 (23.2) | |
5 | 160 (16.8) | 77 (29.8) | 83 (11.9) | |
Co-morbidities (Knaus definitions), n (%)
| ||||
Chronic hepatic failure | 43 (4.5) | 22 (8.5) | 21 (3.0) | 0.0003 |
Chronic heart failure | 107 (11.2) | 38 (14.7) | 69 (9.9) | 0.04 |
Chronic respiratory failure | 167 (17.5) | 55 (21.2) | 112 (16.1) | 0.06 |
Chronic renal failure | 19 (2.0) | 7 (2.7) | 12 (1.7) | 0.33 |
Diabetes | 123 (12.9) | 40 (15.4) | 83 (11.9) | 0.15 |
≥ One co-morbidity | 352 (36.8) | 124 (47.9) | 228 (32.7) | <0.0001 |
Smokers ( >20 pack-year), n (%) | 243 (30.6) | 57 (26.6) | 186 (32.1) | 0.14 |
Alcohol ( >80 g/day), n (%) | 189 (23.8) | 44 (20.6) | 145 (25.0) | 0.19 |
Sepsis, n (%) | 928 (97.1) | 252(97.3) | 676 (97.0) | 0.80 |
Severe sepsis, n (%) | 828 (86.6) | 235 (90.7) | 593 (85.1) | 0.02 |
Septic shock, n (%) | 325 (34.0) | 132 (51.0) | 193 (27.7) | <0.0001 |
Treatments, n (%) unless otherwise stated
| ||||
Invasive ventilation | 604 (63.3) | 207 (79.9) | 397 (57.0) | <0.0001 |
Noninvasive ventilation | 107 (11.2) | 25 (9.7) | 82 (11.8) | 0.36 |
Inotropes or vasoactive agents | 422 (44.1) | 167 (64.5) | 255 (36.6) | <0.0001 |
Corticosteroids | 182 (19.0) | 66 (25.5) | 116 (16.6) | 0.002 |
Hemodialysis/hemofiltration | 63 (6.6) | 33 (12.7) | 30 (4.3) | <0.0001 |
Antibiotic therapy duration in days (median [IQR]) | 7 [4; 13] | 8 [3; 15] | 7 [4; 13] | 0.69 |
Organisms, n (%)
| ||||
Streptococcus pneumoniae
| 202 (21.1) | 52 (20.1) | 150 (21.5) | 0.63 |
Staphylococcus aureus
| 104 (10.9) | 31(12.0) | 73 (10.5) | 0.51 |
Streptococcus spp. | 36 (3.8) | 12 (4.6) | 24 (3.4) | 0.39 |
Enterocococcus spp. | 3 (0.3) | 0 | 3 (0.4) | 0.29 |
Hemophilus influenzae
| 97 (10.1) | 25 (9.7) | 72 (10.3) | 0.76 |
Escherichia coli
| 34 (3.6) | 16 (6.2) | 18 (2.6) | 0.008 |
Enterobacter spp. | 13 (1.4) | 6 (2.3) | 7 (1.0) | 0.12 |
Klebsiella pneumoniae
| 28 (2.9) | 13 (5.0) | 15 (2.2) | 0.02 |
Serratia marescens
| 4 (0.4) | 0 (0) | 4 (0.6) | 0.22 |
Proteus mirabilis
| 9 (0.9) | 5 (1.9) | 4 (0.6) | 0.05 |
Pseudomonas aeruginosa
| 29 (3.0) | 16 (6.2) | 13 (1.9) | 0.0005 |
Legionella pneumophila
| 25 (2.6) | 4 (1.5) | 21 (3.0) | 0.21 |
Mycoplasma pneumoniae
| 1 (0.1) | 0 (0) | 1 (0.1) | 0.54 |
Chlamydia pneumoniae
| 2 (0.2) | 1 (0.4) | 1 (0.1) | 0.47 |
Aspergillus fugimatus
| 3 (0.3) | 2 (0.8) | 1 (0.1) | 0.12 |
Mycobacterium tuberculosis
| 14 (1.5) | 3 (1.2) | 11 (1.6) | 0.63 |
Viruses | 24 (2.5) | 3 (1.2) | 21 (3.0) | 0.10 |
Other | 14 (1.5) | 4 (1.5) | 10 (1.4) | 0.90 |
Multiple organisms | 92 (9.6) | 29 (11.2) | 63 (9.0) | 0.31 |
None identified | 418 (43.7) | 99 (38.2) | 319 (45.8) | 0.04 |
Bacteremia | 121 (12.7) | 45 (17.4) | 76 (10.9) | 0.008 |
Acquisition of MDR pathogen or nosocomial pneumonia, n (%)
| ||||
MDR bacteria | 105 (11.0) | 34 (13.1) | 71(10.2) | 0.19 |
MRSA | 25 (2.6) | 9 (3.5) | 16 (2.3) | 0.31 |
Enterobacteriaceae ESBL | 38 (4.0) | 15 (5.8) | 23 (3.3) | 0.08 |
Nonfermentative GNB | 56 (5.9) | 16 (6.2) | 40 (5.7) | 0.80 |
Clostridium difficile
| 9 (0.9) | 2 (0.8) | 7 (1.0) | 0.74 |
Nosocomial pneumonia | 127 (13.3) | 48 (18.5) | 79 (11.3) | 0.004 |
ICU stay in days, median [IQR] | 7 [3; 15] | 8 [3; 17] | 6 [3; 14] | 0.45 |
Hospital stay in days, median [IQR] | 16 [8; 31] | 10 [4; 22] | 18 [10; 38] | <0.0001 |
Impact of initial adequate antibiotic therapy on 60-day mortality
Multivariate analysis (n = 898) | sHR (95% CI) | P- value |
---|---|---|
Inadequate antibiotic therapy (reference)
| 0.63 (0.42 to 0.94) |
0.02
|
Initial adequate antibiotic therapy
| ||
Secondary adequate antibiotic therapy
| 0.69 (0.37 to 1.27) | 0.23 |
SAPSII per 10 points | 1.65 (1.53 to 1.77) | <.0001 |
Female gender | 0.70 (0.52 to 0.94) | 0.02 |
At least one co-morbidity | 1.49 (1.13 to 1.97) | 0.005 |
Adequate antibiotic therapy on day 2 versus day 1 | 1.33 (0.92 to 1.93) | 0.13 |
Adequate antibiotic therapy on day 3 versus day 1 | 1.29 (0.76 to 2.20) | 0.35 |
Corticosteroids | 0.98 (0.72 to 1.32) | 0.87 |
Impact of one vs. two initial antibiotics on 60-day mortality
Monotherapy (β-lactam) | Dual therapy | |||
---|---|---|---|---|
Parameters | Total population (n = 471) | Total population (n = 394) | β-lactam + Macrolide (n = 164) | β-lactam + Fluoroquino-lone (n = 230) |
Variables at admission
| ||||
Male, n (%) | 301 (63.9) | 274 (69.5) | 110 (67.1) | 164 (71.3) |
Age in years, median [IQR] | 60 [45; 75] | 64 [48; 77] | 64 [49; 79] | 64 [47; 76] |
Scores, n (%)
| ||||
SAPSII*£ | 47 [34; 60] | 39.5 [28; 57] | 37 [28.5; 51] | 43[28; 63] |
SOFA score£ | 6 [4; 9] | 6 [3; 9] | 5 [3; 8] | 7 [4; 10] |
LOD score*£ | 5 [3; 7] | 4 [2; 7] | 3 [2; 5.5] | 4 [2; 8] |
Coma Glasgow Scale*£ | 8 [4; 15] | 15 [8.5; 15] | 15 [11;15] | 14 [7; 15] |
McCabe, n (%)
| ||||
1 | 326 (69.2) | 284 (72.4) | 119 (73.5) | 165 (71.7) |
2 | 124 (26.3) | 98 (25.0) | 40 (24.7) | 58 (25.2) |
3 | 21 (4.5) | 10 (2.6) | 3 (1.9) | 7 (3.0) |
CURB-65,* n (%)
| ||||
0 | 3 (0.6) | 7 (1.8) | 1 (0.6) | 6 (2.6) |
1 | 20 (4.2) | 38 (9.6) | 15 (9.1) | 23 (10.0) |
2 | 88 (18.7) | 71 (18.0) | 34 (20.7) | 37 (16.1) |
3 | 157 (33.3) | 107 (27.2) | 42 (25.6) | 65 (28.3) |
4 | 122 (25.9) | 107 (27.2) | 46 (28.0) | 61 (26.5) |
5 | 81 (17.2) | 64 (16.2) | 26 (15.9) | 38 (16.5) |
Co-morbidities (Knaus definitions), n (%)
| ||||
Chronic hepatic failure£ | 23 (4.9) | 17 (4.3) | 3 (1.8) | 14 (6.1) |
Chronic heart failure | 47 (10.0) | 48 (12.2) | 25 (15.2) | 23 (10.0) |
Chronic respiratory failure*£ | 65 (13.8) | 86 (21.8) | 52 (31.7) | 34 (14.8) |
Chronic renal failure | 9 (1.9) | 7 (1.8) | 3 (1.8) | 4 (1.7) |
Diabetes | 58 (12.3) | 48 (12.2) | 16 (9.8) | 32 (13.9) |
≥One co-morbidity* | 153 (32.5) | 161 (40.9) | 75 (45.7) | 86 (37.4) |
Smokers (>20 pack-years), n (%) | 114 (31.1) | 97 (28.1) | 41 (29.3) | 56 (27.3) |
Alcohol (>80 g/d)* n (%) | 101 (27.6) | 73 (21.2) | 31 (22.1) | 42 (20.5) |
Sepsis, n (%) | 458 (97.2) | 383 (97.2) | 158 (96.3) | 225 (97.8) |
Severe sepsis, n (%) * | 395 (83.9) | 360 (91.4) | 146 (89) | 214 (93.0) |
Septic shock, n (%)* | 146 (31.0) | 152(38.6) | 55 (33.5) | 97(42.2) |
Treatments, n (%) unless otherwise stated
| ||||
Invasive ventilation*£ | 340 (72.2) | 207 (52.5) | 73 (44.5 | 134 (58.3) |
Noninvasive ventilation* | 40 (8.5) | 58 (14.7) | 27 (16.5) | 31 (13.5) |
Inotropes or vasoactive agents*£ | 189 (40.1) | 191 (48.5) | 67 (40.9) | 124 (53.9) |
Corticosteroids* | 69 (14.6) | 96 (24.4) | 40 (24.4) | 56 (24.3) |
Hemodialysis/Hemofil-tration | 23 (4.9) | 31 (7.9) | 11 (637) | 20 (8.7) |
Antibiotic therapy duration in days, median [IQR]* | 7 [4; 13] | 8 [4; 14] | 7 [4; 13] | 8 [4; 15] |
Organisms, n (%)
| ||||
Streptococcus pneumoniae*
£
| 125 (26.5) | 69 (17.5) | 42 (25.6) | 27 (11.7) |
Staphylococcus aureus*
£
| 65 (13.8) | 25 (6.3) | 5 (3.0) | 20 (8.7) |
Streptococcus spp.
| 22 (4.7) | 9 (2.3) | 2 (1.2) | 7 (3.0) |
Enterocococcus spp. | 3 (0.6) | 0 (0) | 0 (0) | 0 (0) |
Hemophilus influenzae*
| 57 (12.1) | 29 (7.4) | 15 (9.1) | 14 (6.1) |
Klebsiella pneumoniae
| 16 (3.4) | 8 (2.0) | 3 (1.8) | 5 (2.2) |
Escherichia coli
| 23 (4.9) | 10 (2.5) | 2 (1.2) | 8 (3.5) |
Enterobacteriaceae spp.* | 11 (2.3) | 2 (0.5) | 1 (0.6) | 1 (0.4) |
Serratia marescens
| 3 (0.6) | 1 (0.3) | 0 (0) | 1 (0.4) |
Proteus mirabilis
| 7 (1.5) | 1 (0.3) | 0 (0) | 1 (0.4) |
Pseudomonas aeruginosa
| 13 (2.8) | 14 (3.6) | 5 (3.0) | 9 (3.9) |
Legionella pneumophila*
| 1 (0.2) | 9 (2.3) | 5 (3.0) | 4 (1.7) |
Mycoplasma pneumoniae
| 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Chlamydia pneumoniae
| 0 (0)) | 2 (0.5) | 0 (0) | 2 (0.9) |
Mycobacterium tuberculosis
£
| 3 (0.6) | 6 (1.5) | 5 (3.0) | 1 (0.4) |
Aspergillus fumigatus
| 0 (0) | 3 (0.8) | 2 (1.2) | 1 (0.4) |
Viruses* | 6 (1.3) | 15 (3.8) | 7 (4.3) | 8 (3.5) |
Other | 6 (1.3) | 6 (1.5) | 1 (06) | 5 (2.2) |
Multiple organisms* | 62 (13.2) | 22 (5.6) | 8 (4.9) | 14 (6.1) |
None identified* | 182 (38.6) | 207 (52.5) | 77 (47.0) | 130 (56.5) |
Bacteremia* | 74 (15.7) | 42 (10.7) | 15 (9.1) | 27 (11.7) |
Acquisition of MDR pathogens or nosocomial pneumonia, n (%)
| ||||
MDR bacteria | 52 (11.0) | 44 (11.2) | 19 (11.6) | 25 (10.9) |
MRSA | 12 (2.5) | 12 (3.0) | 5 (3.0) | 7 (3) |
Enterobacteriaceae ESBL | 22 (4.7) | 12 (3.0) | 5 (3.0) | 7 (3) |
Nonfermentative GNB | 25 (5.3) | 25 (6.3) | 14 (8.5) | 11 (4.8) |
Clostridium difficile
| 6 (1.3) | 2 (0.5) | 0 (0) | 2 (0.9) |
Nosocomial pneumonia | 58 (12.3) | 54 (13.7) | 23 (14) | 31 (13.5) |
ICU stay in days, median [IQR]
| 6 [3; 15] | 7 [3; 16] | 7 [3.5; 15.5] | 8 [3; 17] |
Hospital stay in days, median [IQR]
| 15 [8; 33] | 18 [10; 31] | 17.5 [10.5; 35] | 18 [9; 30] |
Patients who died within 60 days,
£
n (%)
| 123 (26.1) | 107 (27.2) | 35 (21.3) | 72 (31.3) |
Multivariate analysis | sHR | 95% CI | P- value |
---|---|---|---|
Dual therapy versus monotherapy | 1.14 | 0.86 to 1.50 | 0.37 |
SAPSII (per 10 points) | 1.66 | 1.54 to 1.79 | <.0001 |
Female gender | 0.72 | 0.53 to 0.96 | 0.03 |
≥One co-morbidity | 1.43 | 1.07 to 1.91 | 0.01 |
Antibiotic therapy on Day 2 versus Day 1 | 1.38 | 0.98 to 1.93 | 0.07 |
Antibiotic therapy on Day 3 versus Day 1 | 1.28 | 0.75 to 2.19 | 0.36 |
Steroids | 0.97 | 0.71 to 1.32 | 0.83 |
Multivariate sensitivity analysis*
|
sHR
|
(95% CI)
|
P
-value
|
Restricted to Streptococcus pneumoniae infection | 1.42 | 0.73 to 2.77 | 0.31 |
Restricted to documented infection | 1.29 | 0.89 to 1.89 | 0.18 |
Restricted to patients with septic shock | 1.11 | 0.75 to 1.64 | 0.59 |