Background
Methods
Study design and population
Patient identification and inclusion
Definitions
Data collection, follow-up and patient outcomes
Desciption of statistical methods
Results
Demographic and clinical characteristics
Parametersa | Total (n = 214) | Sepsis (n = 83) | Severe sepsis (n = 70) | Septic shock (n = 61) | p value |
---|---|---|---|---|---|
Age (years, median ± IQR, min–max) | 60.0 ± 33.1 (18–93) | 58.5 ± 26.5 (20–92) | 61.3 ± 36.5 (18–95) | 62.0 ± 26.5 (25–90) | 0.58 |
Male gender | 92 (43.0) | 31 (37.3) | 34 (48.6) | 27 (44.3) | 0.36 |
Comorbidities: | |||||
- Arterial hypertension | 132 (61.7) | 51 (61.4) | 44 (62.9) | 37 (60.7) | 0.96 |
- Chronic heart disease | 94 (43.9) | 30 (36.1) | 34 (48.6) | 30 (49.2) | 0.18 |
- Chronic lung disease | 34 (15.9) | 11 (13.3) | 12 (17.1) | 11 (18.0) | 0.69 |
- Chronic kidney disease | 50 (23.4) | 15 (18.1) | 21 (30.0) | 14 (23.0) | 0.22 |
- Chronic liver disease | 55 (25.7) | 13 (15.7) | 21 (30.0) | 21 (34.4) | 0.02* |
- Diabetes mellitus | 61 (28.5) | 24 (28.9) | 24 (34.3) | 13 (21.3) | 0.26 |
- Malignancy | 22 (10.3) | 11 (13.3) | 6 (8.6) | 5 (8.2) | 0.52 |
- Chronic corticosteroid use | 17 (7.9) | 2 (2.4) | 11 (15.7) | 4 (6.6) | 0.01** |
- Immunosuppression | 57 (26.6) | 18 (21.7) | 24 (34.3) | 15 (24.6) | 0.19 |
- Cerebrovascular disease | 58 (27.1) | 22 (26.5) | 13 (18.6) | 23 (37.7) | 0.04*** |
- Intravenous drug use | 7 (3.3) | 2 (2.4) | 4 (5.7) | 1 (1.6) | 0.36 |
- Excess alcohol use | 45 (21.0) | 13 (15.7) | 13 (18.6) | 19 (31.1) | 0.06 |
No. of comorbidities (per patient, median ± IQR, min–max) | 3.0 ± 3.0 (0–8) | 2.0 ± 3.0 (0–7) | 3.5 ± 4.0 (0–8) | 3.0 ± 3.0 (0–7) | 0.07 |
Charlson score (median ± IQR, min–max) | 4.0 ± 5.0 (0–12) | 3.0 ± 5.0 (0–10) | 4.5 ± 5.0 (0–12) | 5.0 ± 5.0 (0–10) | 0.17 |
Source of sepsis: | |||||
Head or neck source | 29 (13.6) | 13 (15.7) | 10 (14.3) | 6 (9.8) | 0.58 |
- Meningitis | 24 (11.2) | 10 (12.0) | 8 (11.4) | 6 (9.8) | |
- Tonsillopharyngitis | 4 (1.9) | 3 (3.6) | 1 (1.4) | 0 | |
- Otitis media | 1 (0.5) | 0 | 1 (1.4) | 0 | |
Thoracic source | 30 (14.0) | 11 (13.3) | 10 (14.3) | 9 (14.8) | 0.96 |
- Pneumonia | 28 (13.1) | 10 (12.0) | 9 (12.9) | 9 (14.8) | |
- Endocarditis | 2 (0.9) | 1 (1.2) | 1 (1.4) | 0 | |
Abdominal source | 52 (24.3) | 13 (15.7) | 16 (22.9) | 23 (37.7) | 0.01* |
- Peritonitis | 12 (5.6) | 2 (2.4) | 1 (1.4) | 9 (14.8) | |
- Cholangitis | 19 (8.9) | 5 (6.0) | 8 (11.4) | 6 (9.8) | |
- Colonic perforation | 2 (0.9) | 0 | 0 | 2 (3.3) | |
- Oesophagitis | 1 (0.5) | 1 (1.2) | 0 | 0 | |
- Enterocolitis | 18 (8.4) | 5 (6.0) | 7 (10.0) | 6 (9.8) | |
Skin and soft tissue source | 20 (9.3) | 8 (9.6) | 5 (7.1) | 7 (11.5) | 0.69 |
- Cellulitis | 17 (7.9) | 6 (7.2) | 4 (5.7) | 7 (11.5) | |
- Diabetic foot infection | 3 (1.4) | 2 (2.4) | 1 (1.4) | 0 | |
Urogenital source | 53 (24.8) | 26 (31.3) | 18 (25.7) | 9 (14.8) | 0.07 |
- Urinary tract infection | 50 (23.4) | 23 (27.7) | 18 (25.7) | 9 (14.8) | |
- Pelvic inflammatory disease | 3 (1.4) | 3 (3.6) | 0 | 0 | |
Toxic shock syndrome | 6 (2.8) | 0 | 2 (2.9) | 4 (6.6) | 0.06 |
Unknown source | 24 (11.2) | 12 (14.5) | 9 (12.9) | 3 (4.9) | 0.17 |
Signs of sepsis: | |||||
- Fever | 192 (89.7) | 74 (89.2) | 66 (94.3) | 52 (85.2) | 0.23 |
- Hypothermia | 2 (0.9) | 0 | 2 (2.9) | 0 | n.a. |
- Euthermia | 21 (9.8) | 9 (10.8) | 3 (4.3) | 9 (14.8) | 0.12 |
- Hypotension | 135 (63.1) | 27 (32.5) | 47 (67.1) | 61 (100.0) | < 0.01*,**,*** |
- Tachycardia | 135 (63.1) | 33 (39.8) | 46 (65.7) | 56 (91.8) | < 0.01*,**,*** |
- Tachypnea | 90 (42.1) | 16 (19.3) | 36 (51.4) | 38 (62.3) | < 0.01*,** |
- Oliguria | 69 (32.2) | 6 (7.2) | 22 (31.4) | 41 (67.2) | < 0.01*,**,*** |
- Altered mental status | 84 (39.3) | 16 (19.3) | 25 (35.7) | 43 (70.5) | < 0.01*,*** |
- Acute abdomen | 26 (12.1) | 7 (8.4) | 8 (11.4) | 11 (18.0) | 0.18 |
- Bleeding | 18 (8.4) | 3 (3.6) | 3 (4.3) | 12 (19.7) | 0.01*,*** |
- Skin lesion | 56 (26.2) | 16 (19.3) | 16 (22.9) | 24 (39.3) | 0.02* |
- Peripheral oedema | 41 (19.2) | 10 (12.0) | 13 (18.6) | 18 (29.5) | 0.03* |
- Splenomegaly | 50 (23.4) | 16 (19.3) | 17 (24.3) | 17 (27.9) | 0.47 |
Microbiological characteristics
Pathogensa | Total (n = 214) | Sepsis (n = 83) | Severe sepsis (n = 70) | Septic shock (n = 61) | p value |
---|---|---|---|---|---|
E. coli | 60 (28.0) | 25 (30.1) | 21 (30.0) | 14 (23.0) | 0.89 |
S. pneumoniae | 18 (8.4) | 4 (4.8) | 6 (8.6) | 8 (13.1) | 0.79 |
S. aureus | 14 (6.5) | 7 (8.4) | 3 (4.3) | 4 (6.6) | 0.99 |
K. pneumoniae | 12 (5.6) | 2 (2.4) | 5 (7.1) | 5 (8.2) | 0.98 |
S. Enteritidis | 10 (4.7) | 2 (2.4) | 5 (7.1) | 3 (4.9) | 1.0 |
S. pyogenes | 8 (3.7) | 2 (2.4) | 3 (4.3) | 3 (4.9) | 1.0 |
N. meningitidis | 5 (2.3) | 2 (2.4) | 2 (2.9) | 1 (1.6) | 1.0 |
L. monocytogenes | 3 (1.4) | 1 (1.2) | 1 (1.4) | 1 (1.6) | 1.0 |
K. oxytoca | 3 (1.4) | 0 | 1 (1.4) | 2 (3.3) | 1.0 |
P. mirabilis | 3 (1.4) | 0 | 2 (2.9) | 1 (1.6) | 1.0 |
S. anginosus | 2 (0.9) | 0 | 1 (1.4) | 1 (1.6) | 1.0 |
C. jejuni | 2 (0.9) | 0 | 0 | 2 (3.3) | n.a. |
L. pneumophila | 2 (0.9) | 0 | 1 (1.4) | 1 (1.6) | 1.0 |
S. agalactiae | 2 (0.9) | 2 (2.4) | 0 | 0 | n.a. |
F. necrophorum | 2 (0.9) | 2 (2.4) | 0 | 0 | n.a. |
West Nile virus | 2 (0.9) | 2 (2.4) | 0 | 0 | n.a. |
S. mitis | 2 (0.9) | 2 (2.4) | 0 | 0 | n.a. |
S. dysgalactiae | 1 (0.5) | 1 (1.2) | 0 | 0 | n.a. |
C. difficile | 1 (0.5) | 0 | 0 | 1 (1.6) | n.a. |
P. aeruginosa | 1 (0.5) | 0 | 0 | 1 (1.6) | n.a. |
B. thetaiotamicron | 1 (0.5) | 0 | 0 | 1 (1.6) | n.a. |
C. albicans | 1 (0.5) | 1 (1.2) | 0 | 0 | n.a. |
C. canimorsus | 1 (0.5) | 0 | 0 | 1 (1.6) | n.a. |
E. cloaceae | 1 (0.5) | 1 (1.2) | 0 | 0 | n.a. |
P. multocida | 1 (0.5) | 1 (1.2) | 0 | 0 | n.a. |
S. marcescens | 1 (0.5) | 0 | 1 (1.4) | 0 | n.a. |
Antimicrobial and supportive therapies
Parametersa | Total (n = 214) | Sepsis (n = 83) | Severe sepsis (n = 70) | Septic shock (n = 61) | p value |
---|---|---|---|---|---|
In-hospital mortality | 30 (14.0) | 0 | 4 (5.7) | 26 (42.6) | < 0.01**,*** |
Time to death from admission (days, median ± IQR, min–max) | 8.0 ± 12.5 (1–40) | 0 | 5.0 ± 8.8 (2–19) | 7.0 ± 10.8 (1–40) | 0.6 |
ICU admittance | 58 (27.1) | 7 (8.4) | 16 (22.9) | 35 (57.4) | < 0.01*,**,*** |
LOS (days, median ± IQR, min–max) | 10.0 ± 8.0 (1–123) | 10.0 ± 7.5 (3–80) | 10.0 ± 6.0 (1–123) | 7.0 ± 13.8 (1–80) | 0.96 |
ICU LOS (days, median ± IQR, min–max) | 8.0 ± 10.8 (1–60) | 9.0 ± 14.5 (2–22) | 9.0 ± 7.0 (1–50) | 8.0 ± 11.0 (1–60) | 0.95 |
Rate of source control | 39 (18.2) | 13 (15.7) | 13 (18.6) | 13 (21.3) | 0.76 |
Rate of bacteraemia | 109 (50.9) | 37 (44.6) | 40 (57.1) | 32 (52.5) | 0.29 |
No. of patients receiving antimicrobial therapy | 212 (99.1) | 82 (98.8) | 70 (100) | 60 (98.4) | 0.44 |
Duration of antibiotic therapyb (days, median ± IQR, min–max) | 10.0 ± 5.0 (1–50) | 10.5 ± 4.0 (4–50) | 10.0 ± 5.0 (2–28) | 12.5 ± 13.0 (1–30) | 0.61 |
Types of empirical antimicrobial therapy: | |||||
- Penicillins | 26 (12.3) | 15 (18.3) | 3 (4.3) | 8 (13.3) | 0.02* |
- Cephalosporins | 153 (72.2) | 56 (68.3) | 55 (78.6) | 42 (70.0) | 0.7 |
- Carbapenems | 16 (7.6) | 1 (1.2) | 5 (7.1) | 10 (16.7) | 0.01** |
- Aminoglycosides | 5 (2.4) | 4 (4.8) | 1 (1.4) | 0 | 0.99 |
- Macrolides | 1 (0.5) | 0 | 0 | 1 (1.7) | 1.0 |
- Fluoroquinolones | 25 (11.8) | 12 (14.6) | 9 (12.9) | 4 (6.7) | 1.0 |
- Tetracyclines | 2 (1.0) | 0 | 1 (1.4) | 1 (1.7) | 0.97 |
- Metronidazol | 11 (5.2) | 3 (3.6) | 3 (4.3) | 5 (8.3) | 0.99 |
- Clindamycin | 7 (3.3) | 1 (1.2) | 1 (1.4) | 5 (8.3) | 0.88 |
- Vancomycin | 20 (9.4) | 6 (7.3) | 5 (7.1) | 9 (15.0) | 0.99 |
- Fluconazole | 1 (0.5) | 1 (1.2) | 0 | 0 | 1.0 |
Characteristics of antimicrobial therapy: | |||||
- No. of empirical combinations | 45 (21.2) | 14 (17.1) | 11 (15.7) | 20 (33.3) | 0.06 |
- No. of adequate empirical antimicrobial therapy | 190 (89.6) | 74 (90.2) | 63 (90.0) | 53 (88.3) | 0.84 |
- No. of escalations of antimicrobial therapy | 36 (16.9) | 9 (10.9) | 14 (20.0) | 13 (21.6) | 0.17 |
- No. of de-escalations of antimicrobial therapy | 30 (14.2) | 12 (14.6) | 4 (5.7) | 14 (23.3) | 0.02*** |
- No. of patients with subsequent oral switch | 55 (25.9) | 25 (30.5) | 21 (30.0) | 9 (15.0) | 0.06 |
No. of patients receiving supportive therapy | 87 (40.7) | 15 (18.1) | 28 (40.0) | 44 (72.1) | < 0.01*,**,*** |
Types of supportive therapy: | |||||
- Hemodynamical support | 47 (22.0) | 0 | 2 (2.9) | 45 (73.8) | < 0.01**, |
- Mechanical ventilation | 40 (18.7) | 2 (2.4) | 10 (14.3) | 28 (45.9) | < 0.01*,**,*** |
- Renal replacement therapy | 6 (2.8) | 0 | 1 (1.4) | 5 (8.2) | 0.01** |
- Any corticosteroid therapy | 33 (15.4) | 10 (12.0) | 14 (20.0) | 9 (14.8) | 0.39 |
- Human albumin | 17 (7.9) | 2 (2.4) | 3 (4.3) | 12 (19.7) | < 0.01**,*** |
- Red blood cell transfusion | 43 (20.1) | 5 (6.0) | 12 (17.1) | 26 (42.6) | < 0.01**,*** |
- Thrombocyte transfusion | 15 (7.0) | 1 (1.2) | 2 (2.9) | 12 (19.7) | < 0.01**,*** |
Duration of supportive therapy (days, median ± IQR, min–max): | |||||
- Hemodynamical support | 4.0 ± 7.0 (1–30) | 0 | 2.0 ± 1.0 (1–3) | 4.5 ± 8.3 (1–30) | 0.11 |
- Mechanical ventilation | 7.0 ± 8.0 (1–27) | 12.5 ± 4.5 (8–17) | 7.0 ± 5.5 (1–20) | 7.0 ± 10.5 (1–27) | 0.66 |
- Renal replacement therapy | 7.5 ± 8.8 (1–15) | 0 | 1 (1–1) | 10.0 ± 9.0 (4–15) | 0.33 |
- Any corticosteroid therapy | 5.0 ± 6.0 (1–20) | 6.0 ± 5.0 (3–14) | 5.0 ± 3.0 (2–20) | 6.0 ± 9.5 (1–18) | 0.68 |
- Human albumin | 4.0 ± 2.0 (1–10) | 3.5 ± 1.5 (2–5) | 5.0 ± 1.5 (3–6) | 4.0 ± 2.0 (1–10) | 0.73 |
Clinical outcomes
Parametersa | Survival (n = 184) | Exitus (n = 30) | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
OR (95% CI) | p value | OR (95% CI) | p value | |||
Age (years, median ± IQR, min–max) | 58.4 ± 34.0 (18–93) | 66.7 ± 21.0 (26–90) | 0.98 (0.96–1.01) | 0.06 | – | – |
Male gender | 76 (41.3) | 16 (53.3) | 1.62 (0.75–3.52) | 0.22 | 6.35 (1.24–32.51) | 0.03 |
Arterial hypertension | 109 (59.2) | 23 (76.7) | 2.22 (0.9–5.26) | 0.09 | – | – |
Chronic heart disease | 78 (42.4) | 16 (53.3) | 1.56 (0.72–3.45) | 0.27 | ||
Chronic lung disease | 25 (13.6) | 9 (30.0) | 2.7 (1.11–6.66) | 0.03 | – | – |
Chronic kidney disease | 43 (23.4) | 7 (23.3) | 1.0 (0.4–2.49) | 0.99 | ||
Chronic liver disease | 44 (23.9) | 11 (36.7) | 1.85 (0.81–4.17) | 0.14 | ||
Diabetes mellitus | 52 (28.3) | 9 (30.0) | 1.09 (0.13–2.56) | 0.85 | ||
Malignancy | 20 (10.9) | 2 (6.7) | 0.59 (0.13–2.63) | 0.49 | ||
Corticosteroid use | 14 (7.6) | 3 (10.0) | 1.35 (0.36–5.0) | 0.65 | ||
Immunosuppression | 46 (25.0) | 11 (36.7) | 1.72 (0.76–3.85) | 0.19 | ||
Cerebrovascular disease | 44 (23.9) | 14 (46.7) | 2.78 (1.27–6.25) | 0.01 | – | – |
Intravenous drug use | 7 (3.8) | 0 | n.a. | n.a. | ||
Excess alcohol use | 33 (17.9) | 12 (40.0) | 3.0 (1.33–7.14) | 0.01 | – | – |
No. of comorbidities (per patient, median ± IQR, min–max) | 3.0 ± 3.0 (0–8) | 4.0 ± 2.0 (0–7) | 1.32 (1.06–1.61) | 0.08 | – | – |
Charlson score (median ± IQR, min–max) | 4.0 ± 5.3 (0–12) | 6.0 ± 4.8 (0–9) | 1.11 (0.98–1.28) | 0.09 | – | – |
Absence of fever at diagnosis | 14 (7.6) | 8 (26.7) | 4.42 (1.67–11.71) | 0.01 | 7.35 (1.1–51.8) | 0.04 |
Presence of shock at diagnosis | 35 (19.0) | 26 (86.7) | 27.78 (9.09–83.3) | < 0.01 | 33.93 (6.72–141.47) | < 0.01 |
Identifiable source of sepsis | 163 (88.6) | 27 (90.0) | 1.16 (0.32–4.17) | 0.82 | – | – |
Source control | 36 (19.6) | 3 (10.0) | 0.46 (0.13–1.59) | 0.22 | 0.09 (0.01–0.63) | 0.02 |
Rate of bacteraemia | 92 (50.0) | 17 (56.7) | 1.29 (0.59–2.86) | 0.49 | – | – |
Need for ICU admittance | 36 (19.6) | 22 (73.3) | 11.11 (4.55–25.0) | < 0.01 | 8.39 (1.67–42.05) | 0.01 |
Need for supportive therapy | 63 (34.2) | 24 (80.0) | 7.69 (2.94–20.0) | < 0.01 | – | – |
Duration of antibiotic therapy (days, median ± IQR, min–max) | 11.0 ± 4.0 (1–50) | 6.5 ± 12.8 (1–30) | 1.09 (1.02–1.19) | 0.01* | n.a. | |
Adequate empirical antimicrobial therapy | 164 (89.1) | 26 (86.7) | 0.71 (0.22–2.27) | 0.56 | – | – |
Escalation of antimicrobial therapy | 28 (15.2) | 8 (26.7) | 2.0 (0.81–5.0) | 0.13 | – | – |
De-escalation of antimicrobial therapy | 27 (14.7) | 3 (10.0) | 0.64 (0.18–2.27) | 0.48 | 0.14 (0.02–1.06) | 0.04 |
Empirical antimicrobial combinations | 37 (20.1) | 8 (26.7) | 1.42 (0.59–3.45) | 0.43 | ||
Penicillins as empirical choice | 22 (12.0) | 4 (13.3) | 1.13 (0.36–3.57) | 0.83 | ||
Cephalosporins as empirical choice | 129 (70.1) | 24 (80.0) | 1.69 (0.74–4.35) | 0.38 | ||
Carbapenems as empirical choice | 13 (7.1) | 3 (10.0) | 1.47 (0.39–5.56) | 0.57 |