Demographics and clinical characteristics of the overall cohort
According to the inclusion and exclusion criteria (Fig. 1), the total of 3,898 adults having community-onset bactereamia were enrolled in the present cohort. The median (IQR) age of overall patients was 70 (57–80) years, and male patients (2,018 patients, 51.8%) were predominant. The median (IQR) lengths of ED stay and hospitalization were 15.0 (5.4–26.4) hours and 10 (6–18) days, respectively. Patients experiencing complicated bactereamia accounted for 19.9% (775 patients) of the entire cohort. Patients initially presented with SIRS or qSOFA ≥ 2 respectively accounted for 92.8% (3,619 patients) or 46.9% (1,927) of the overall cohort. The 15-day and 30-day crude mortality rate was 13.6% (530 patients) and 17.2% (670), respectively.
Of the total 3,898 patients, common comorbidities included hypertension (1,915 patients, 49.1%), diabetes mellitus (1,491, 38.3%), malignancies (1,211, 31.1%), neurological disorders (956, 24.5%), chronic kidney diseases (756, 19.4%), liver cirrhosis (478, 12.3%), coronary artery diseases (391, 10.0%), heart failure (359, 9.2%), urological diseases (341, 8.7%), and chronic obstructive pulmonary diseases (214, 5.5%). The leading source of bactereamia was urinary tract infections (1,227, 31.5%), followed by pneumonia (648, 16.6%), skin and soft-tissue infections (438, 11.2%), intra-abdominal infections (433, 11.1%), biliary tract infections (322, 8.3%), primary bactereamia (287, 7.4%), bone and joint infections (152, 3.9%), vascular-line infections (144, 3.7%), liver abscess (138, 3.5%), and infective endocarditis (117, 3.0%).
Because of 390 episodes of polymicrobial bactereamia, the total 4,398 causative microorganisms were identified. The leading ten microorganisms included Escherichia coli (1,528 isolates, 34.7%), Klebsiella pneumoniae (669, 15.2%), Streptococcus species (605, 13.8%), Staphylococcus aureus (511, 11.6%), Pseudomonas species (138, 3.1%), Enterococcus species (130, 3.0%), Proteus species (104, 2.4%), Enterobacter species (101, 2.3%), Salmonella species (66, 1.5%), and Aeromonas species (50, 1.1%).
The time-to-appropriate antibiotic and time-to-source control
The median (IRQ) of the time-to-appropriate antibiotic and time-to-source control was 2 (1–11) hours and 2 (1–10) days, respectively. The period of time-to-appropriate antibiotic in patients initially presented with SIRS scores of ≥ 2 (median, 2 vs. 67 hours, P < 0.001) and qSOFA scores of ≥ 2 (median, 4 vs. 36 hours, P < 0.001) was significantly shorter than those with SIRS scores of < 2 and qSOFA scores of < 2 (Fig. 2A), respectively. Notably, the time-to-appropriate antibiotic in patients initially presented with SIRS scores of ≥ 2 remained significant shorter than those with qSOFA scores of ≥ 2 (median, 2 vs. 4 hours, P < 0.001)
Similarly, the period of the time-to-source control in patients initially with SIRS scores of ≥ 2 (median, 2 vs. 9 hours, P < 0.001) was significantly shorter than those with SIRS scores of < 2 (Fig. 2B). However, the period of the time-to-source control between patients initially experienced qSOFA scores of ≥ 2 and those with qSOFA scores of < 2 did not differ significantly (median, 2 vs. 2 hours, P = 0.89), as shown in Fig. 2B. Of note, the period of the time-to-source control in patients initially with SIRS scores of ≥ 2 (median, 2 vs. 3 hours, P = 0.003) was significantly shorter than those with qSOFA scores of ≥ 2 (Fig. 2B).
Clinical predictors of 30-day mortality
The association of numerous clinical covariates, including patient demographics, the appropriateness of empirical antimicrobial therapy or source control, major bactereamia sources, comorbidity severity, major comorbidities, and the major causative pathogen, with 30-day mortality were examined using univariate analysis (Table 1). The following variables were positively associated with 30-day mortality: the elderly, male patients, nursing-home residents, inappropriate EAT, inadequate source control, bactereamic pneumonia, polymicrobial bactereamia, causative microorganisms of Klebsiella pneumoniae, Staphylococcus aureus, or Pseudomonas species, fatal comorbidities (McCabe classification), and underlying malignancies, neurological diseases, or liver cirrhosis. Otherwise, several factors, including bactereamia caused by urinary tract infections, biliary tract infections, or liver abscess, E. coli bactereamia, and comorbid hypertension, were protective factors against 30-day crude mortality.
Table 1
Predictors of 30-day crude mortality in patients with community-onset bacteremia
Variables
|
Patient numbers (%)
|
Univariate analysis
|
Multivariate analysis
|
Death, n = 670
|
Survival, n = 3228
|
OR (95% CI)
|
P value
|
Adjusted OR (95% CI)
|
P value
|
Patient demographics
|
|
|
|
|
|
|
The elderly, ≥ 65 years
|
442 (66.0)
|
1918 (59.4)
|
1.32 (1.11–1.58)
|
0.002
|
1.28 (1.04–1.58)
|
0.02
|
Gender, male
|
394 (58.8)
|
1624 (50.3)
|
1.41 (1.19–1.67)
|
< 0.001
|
NS
|
NS
|
Nursing-home residents
|
94 (14.0)
|
155 (4.8)
|
3.24 (2.47–4.24)
|
< 0.001
|
1.99 (1.42–2.78)
|
< 0.001
|
Inappropriate empirical antimicrobial therapy
|
117 (26.4)
|
624 (19.3)
|
1.50 (1.24–1.82)
|
< 0.001
|
1.59 (1.27–1.99)
|
< 0.001
|
Inadequate source control
|
42 (6.3)
|
91 (2.8)
|
2.31 (1.58–3.36)
|
< 0.001
|
3.36 (2.19–5.17)
|
< 0.001
|
Major bacteremia sources
|
|
|
|
|
|
|
Pneumonia
|
299 (44.6)
|
349 (10.8)
|
6.65 (5.51–8.03)
|
< 0.001
|
4.35 (3.46–5.45)
|
< 0.001
|
Intra-abdominal
|
75 (11.2)
|
358 (11.1)
|
1.01 (0.78–1.32)
|
0.94
|
–
|
–
|
Urinary tracts
|
72 (10.7)
|
1155 (35.8)
|
0.22 (0.17–0.28)
|
< 0.001
|
0.35 (0.26–0.47)
|
< 0.001
|
Skin and soft-tissue
|
61 (9.1)
|
377 (11.7)
|
0.76 (0.527–1.01)
|
0.06
|
–
|
–
|
Biliary tracts
|
30 (4.5)
|
292 (9.0)
|
0.47 (0.32–0.69)
|
< 0.001
|
0.46 (0.30–0.70)
|
< 0.001
|
Liver abscess
|
8 (1.2)
|
130 (4.0)
|
0.29 (0.14–0.59)
|
< 0.001
|
0.32 (0.15–0.69)
|
0.004
|
Polymicrobial bacteremia
|
119 (17.8)
|
271 (8.4)
|
2.36 (1.87–2.98)
|
< 0.001
|
NS
|
NS
|
Major causative microorganisms
|
|
|
|
|
|
|
Escherichia coli
|
167 (24.9)
|
1360 (42.1)
|
0.46 (0.38–0.55)
|
< 0.001
|
NS
|
NS
|
Klebsiella pneumoniae
|
149 (22.2)
|
519 (16.1)
|
1.49 (1.22–1.83)
|
< 0.001
|
1.24 (0.97–1.59)
|
0.08
|
Staphylococcus aureus
|
121 (19.1)
|
389 (12.1)
|
1.61 (1.29–2.01)
|
< 0.001
|
NS
|
NS
|
Streptococcus species
|
108 (16.1)
|
480 (14.9)
|
1.10 (0.88–1.38)
|
0.41
|
–
|
–
|
Pseudomonas species
|
45 (6.7)
|
93 (2.9)
|
2.43 (1.68–3.50)
|
< 0.001
|
NS
|
NS
|
Enterococcus species
|
24 (3.6)
|
106 (3.3)
|
1.09 (0.70–1.72)
|
0.70
|
–
|
–
|
Fatal comorbidities (McCabe classification)
|
312 (46.6)
|
716 (22.2)
|
3.06 (2.57–3.64)
|
< 0.001
|
2.39 (1.89–3.02)
|
< 0.001
|
Major comorbidities
|
|
|
|
|
|
|
Malignancies
|
308 (46.0)
|
903 (28.0)
|
2.19 (1.85–2.60)
|
< 0.001
|
1.40 (1.11–1.76)
|
0.004
|
Hypertension
|
300 (44.8)
|
1615 (50.0)
|
0.81 (0.69–0.96)
|
0.01
|
0.84 (0.69–1.03)
|
0.10
|
Diabetes mellitus
|
238 (35.5)
|
1253 (38.8)
|
0.87 (0.73–1.03)
|
0.11
|
–
|
–
|
Neurological diseases
|
217 (32.4)
|
739 (22.9)
|
1.61 (1.35–1.93)
|
< 0.001
|
1.35 (1.06–1.71)
|
0.02
|
Chronic kidney diseases
|
134 (20.0)
|
622 (19.3)
|
1.05 (0.85–1.29)
|
0.66
|
–
|
–
|
Liver cirrhosis
|
116 (17.3)
|
362 (11.2)
|
1.66 (1.32 =- 2.08)
|
< 0.001
|
1.52 (1.17–1.99)
|
0.002
|
Coronary artery diseases
|
76 (11.3)
|
315 (9.8)
|
1.18 (0.91–1.54)
|
0.21
|
–
|
–
|
CI = confidence interval; NS = not significant (after processing the backward multivariate regression); |
OR = odds ratio. |
Furthermore, through the multivariate regression model (Table 1), numerous independent determinants of 30-day crude mortality were recognized: the elderly, nursing-home residents, inappropriate EAT, inadequate source control, bactereamic pneumonia, bactereamia due to urinary tract infections, biliary tract infections, or liver abscess, fatal comorbidities (McCabe classification), and comorbid malignancies, neurological diseases, or liver cirrhosis.
Effects of inappropriate EAT and inadequate source control on prognoses of patients categorized by qSOFA or SIRS
After adjustment of the independent predictors of 30-day mortality, recognized in Table 1, significant impacts of inappropriate EAT on 30-day crude mortality were exhibited in patients initially presented with SIRS scores of 2 and 3–4, but not in those of 0–1 (Fig. 3A). Similarly, significant effects of inadequate source control on prognoses were evidenced in patients initially with SIRS scores of 2 and 3–4, but not in those of 0–1 (Fig. 3B).
Notably, adverse impacts of inappropriate EAT (Fig. 4A) and inadequate source control (Fig. 4B) on 30-day crude mortality were all significant in patients initially experienced qSOFA scores of 0–1, 2, and 3, after adjusting all the independent determinates of 30-day mortality.
The discrimination in predicting 30-day mortality by SIRS and qSOFA scores
For prediction of 30-day crude mortality (Fig. 5), the area under the ROC curve is 0.830 (95% confidence interval [CI], 0.812–0.848; P < 0.001) in the qSOFA score and 0.712 (95% CI, 0.689–0.735; P < 0.001) in the SIRS score; thus the ability to discriminate between survivors and fatal patients was proper in the SIRS score and excellent in the qSOFA score.