Patient demographics
After excluding recurrent episodes and polymicrobial bacteremia, there were 293, 88, and 118 episodes of mEB in the hospital A, B and C, respectively, were included for the analysis (Fig. 1). The crude in-hospital mortality rate was similar in three hospitals: 15%, 16%, and 13%, respectively. Overall, this study involved 499 adults with an average age of 75 years and their crude in-hospital mortality rate was 15%. Female gender (263, 53%) predominated. Common comorbidities of the included patients included hypertension, diabetes mellitus, old stroke, chronic kidney diseases, and malignancy, and in this study major microorganisms causing mEB were E. coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, and Citrobacter koseri (Table 1).
Table 1
Factors associated with in-hospital crude mortality in patients with monomicrobial Enterobacteriaceae bacteremia.
Variables | Total | Patient numbers (%) | P value |
n = 499 | Survived, n = 426 | Expired, n = 73 |
Age, years, mean ± SD | 74.5 ± 12.9 | 74.1 ± 13.0 | 77.3 ± 11.5 | 0.05 |
Gender, male | 236 (47.3) | 201 (47.2) | 35 (47.9) | 1.00 |
Comorbidities | | | | |
Hypertension | 286 (57.3) | 246 (57.7) | 40 (54.8) | 0.70 |
Diabetes mellitus | 207 (41.5) | 177 (41.5) | 30 (41.1) | 1.00 |
Old stroke | 105 (21.0) | 86 (20.2) | 19 (26.0) | 0.28 |
Chronic kidney diseases | 79 (15.8) | 64 (15.0) | 15 (20.5) | 0.23 |
Malignancy | 66 (13.2) | 54 (12.7) | 12 (16.4) | 0.36 |
Coronary artery disease history | 58 (11.6) | 48 (11.3) | 10 (13.7) | 0.55 |
Liver cirrhosis | 22 (4.4) | 18 (4.2) | 4 (5.5) | 0.55 |
Congestive heart failure | 14 (2.8) | 13 (3.1) | 1 (1.4) | 0.70 |
Charlson comorbidity index, mean ± SD | 1.2 ± 1.2 | 1.2 ± 1.1 | 1.4 ± 1.3 | 0.15 |
Nosocomial bacteremia | 112 (22.4) | 91 (21.4) | 21 (28.8) | 0.17 |
Time-to-positivity, hours | 25.1 ± 17.4 | 24.5 ± 17.4 | 28.5 ± 19.4 | 0.10 |
Antimicrobial-susceptible isolates | | | | |
Second GCs | 223 (44.7) | 197 (46.2) | 26 (35.6) | 0.10 |
Third GCs | 327 (65.5) | 290 (68.1) | 37 (50.7) | 0.005 |
Fourth GCs | 363 (72.7) | 316 (74.2) | 47 (64.4) | 0.09 |
Amoxicillin/clavulanic acid | 297 (57.5) | 250 (58.7) | 37 (50.7) | 0.20 |
Fluoroquinolones | 259 (51.9) | 224 (52.6) | 35 (47.9) | 0.53 |
Ertapenem | 465 (93.2) | 403 (94.6) | 62 (84.9) | 0.009 |
Major causative microorganisms | | | | |
Escherichia coli | 310 (62.1) | 275 (64.6) | 35 (47.9) | 0.009 |
Klebsiella pneumoniae | 104 (20.8) | 80 (18.8) | 24 (32.9) | 0.008 |
Proteus mirabilis | 31 (6.2) | 27 (6.3) | 4 (5.5) | 1.00 |
Providencia stuartii | 11 (2.2) | 10 (2.3) | 1 (1.4) | 1.00 |
Citrobacter koseri | 8 (1.6) | 7 (1.6) | 1 (1.4) | 1.00 |
GC = generation cephalosporin; SD = standard deviation. |
Data are given as number (percent), unless otherwise specified. |
Boldface indicates statistical significance in the univariate analysis, i.e., a P value of < 0.05. |
Risk Factors Of In-hospital Crude Mortality
As compared with the survivors, fatal patients with mEB were less likely to be infected by 3GC- (68% vs. 51%, P = 0.005) or ertapenem-susceptible isolates (95% vs. 85%, P = 0.009) and E. coli (65% vs. 48%, P = 0.008) (Table 1), but were often associated with K. pneumoniae infections (19% vs. 33%, P = 0.008). No significant association between the in-hospital mortality and patient age, gender male, comorbidity types or Charlson comorbidity index was disclosed. Notably, in the multivariate analysis for risk factors of in-hospital crude mortality, only one independent variable, 3GC-NS, was recognized (adjusted odds ratio [AOR], 1.78; 95% confident interval [CI] 1.02–3.11; P = 0.04) (Table 2).
Table 2
Multivariate analysis of risk factors for in-hospital crude mortality among adults with monomicrobial Enterobacteriaceae bacteremia.
Characters | Adjusted odds ratio | 95% confidence interval | P value |
3GC non-susceptibility | 1.78 | 1.02–3.11 | 0.04 |
Ertapenem non-susceptibility | 1.55 | 0.61–3.91 | 0.36 |
Klebsiella pneumoniae | 1.12 | 0.51–2.49 | 0.78 |
Escherichia coli | 0.60 | 0.31–1.19 | 0.14 |
3GC = third-generation cephalosporin. |
Predictors of 3GC-non-susceptibility among Enterobacteriaceae bacteremia
Patients infected by 3GC-NS isolates were older (mean age: 77 years vs. 74 years; P = 0.009) and more likely to be male gender (58% vs. 42%, P < 0.001), or to have comorbidities of chronic kidney diseases (23% vs. 12%, P = 0.003) or the use of nasogastric tubes (61% vs. 37%, P < 0.001) or urinary catheters (55% vs. 38%, P < 0.001) than those by 3GC-susceptible microorganisms, as shown in Table 3. Otherwise, less episodes of P. mirabilis bacteremia (3% vs. 8%, P = 0.03) and more K. pneumoniae bacteremia (30% vs. 16%, P < 0.001) were noted in patients with 3GC-NS Enterobacteriaceae bacteremia (Table 3). Since chronic kidney disease was the only parameter in Charlson comorbidity index with statistically correlated with 3GC-NS, chronic kidney disease, instead of Charlson comorbidity index, was placed in the multivariate analysis. In the multivariate analysis, male patients (AOR 2.02, 95% CI 1.33–3.05; P = 0.001), nosocomial-acquired bacteremia (AOR 2.77, 95% CI 1.72–4.47; P < 0.001), and usage of nasogastric tube (AOR 2.01, 95% CI 1.28–3.16; P = 0.002) were positively associated with 3GC-NS (Table 4). In contrast, P. mirabilis bacteremic episodes (AOR 0.28, 95% CI 0.10–0.77; P = 0.01) and age (AOR 0.98, 95% CI 0.97–0.99; P = 0.04) were negatively linked to 3GC-NS.
Table 3
Clinical predictors of third-generation cephalosporin-non-susceptibility in the episodes of monomicrobial Enterobacteriaceae bacteremia.
Variables | Patient numbers (%) | P value |
Susceptible, n = 327 | Non-susceptible, n = 172 |
Age, years, mean ± SD | 73.5 ± 13.0 | 76.6 ± 12.3 | 0.009 |
Charlson comorbidity index, mean ± SD | 1.1 ± 1.1 | 1.4 ± 1.2 | 0.007 |
Gender, male | 137 (41.9) | 99 (57.6) | < 0.001 |
Comorbidities | | | |
Hypertension | 190 (58.1) | 96 (55.8) | 0.64 |
Diabetes mellitus | 133 (40.7) | 74 (43.0) | 0.63 |
Old stroke | 68 (20.8) | 37 (21.5) | 0.91 |
Chronic kidney disease | 40 (12.2) | 39 (22.7) | 0.003 |
Malignancy | 43 (13.1) | 23 (13.4) | 1.00 |
Coronary artery disease | 32 (9.8) | 26 (15.1) | 0.08 |
Liver cirrhosis | 12 (3.7) | 10 (5.8) | 0.26 |
Congestive heart failure | 8 (2.4) | 6 (3.5) | 0.57 |
Nosocomial bacteremia | 48 (14.7) | 64 (37.2) | < 0.001 |
Catheter dependence | | | |
Nasogastric tube | 120 (36.9) | 104 (60.8) | < 0.001 |
Urinary catheter | 124 (37.9) | 94 (55.3) | < 0.001 |
Major causative microorganisms | | | |
Escherichia coli | 210 (64.2) | 100 (58.1) | 0.21 |
Klebsiella pneumoniae | 51 (15.6) | 52 (30.2) | < 0.001 |
Proteus mirabilis | 26 (7.9) | 5 (2.9) | 0.03 |
Providencia stuartii | 10 (3.1) | 1 (0.6) | 0.11 |
Citrobacter koseri | 6 (1.8) | 2 (1.2) | 0.72 |
SD = standard deviation. |
* Data are given as number (percent), unless otherwise specified. Boldface indicates statistical significance in the univariate analysis, i.e., a P value of < 0.05. |
Table 4
Multivariate analysis of risk factors of third-generation cephalosporin non-susceptibility among the episodes of monomicrobial Enterobacteriaceae bacteremia.
Characters | Adjusted odds ratio | 95% confidence interval | P value |
Patient demographics | | | |
Male | 2.02 | 1.33–3.05 | 0.001 |
Age, years | 0.98 | 0.97–0.99 | 0.04 |
Nosocomial bacteremia | 2.77 | 1.72–4.47 | < 0.001 |
Catheter dependence | | | |
Nasogastric tubes | 2.01 | 1.28–3.16 | 0.002 |
Urinary catheters | 1.39 | 0.89–2.18 | 0.15 |
Causative microorganisms | | | |
Klebsiella pneumoniae | 1.48 | 0.90–2.45 | 0.13 |
Proteus mirabilis | 0.28 | 0.10–0.77 | 0.01 |
Underlying chronic kidney diseases | 1.58 | 0.93–2.69 | 0.09 |
Antimicrobial Therapy And Clinical Outcomes
The common antimicrobials empirically administered for patients with 3GC-susceptible Enterobacteriaceae bacteremia were 3GCs (32%), 2GCs (16%), and piperacillin-tazobactam (14%). Appropriate empirical (30% vs. 82%, P < 0.001) or definitive (80% vs. 94%, P < 0.001) therapy was less commonly prescribed among patients infected by 3GC-NS isolates, compared to those by 3GC-susceptible isolates (Table 5). Furthermore, patients with 3GC-NS Enterobacteriaceae bacteremia more often had septic shock at presentation (20% vs. 11%, P = 0.007) and had a higher in-hospital crude mortality rate (21% vs. 11%, P = 0.005) than those infected by 3GC-susceptible isolates (Table 5).
Table 5. Bacteremia severity, antimicrobial therapy and outcomes of patients with monomicrobial Enterobacteriaceae bacteremia, stratified by third-generation cephalosporin susceptibility.
Variables
|
Patient numbers (%)
|
P value
|
|
Susceptible, n=327
|
Non-susceptible, n=172
|
Bacteremia severity
|
|
|
|
Blood leukocyte, x103/mm3, mean ± SD
|
13.3 ± 7.4
|
13.0 ± 6.0
|
0.72
|
Time-to-positivity, hours, mean ± SD (n=392)
|
24.5 ± 16.6
|
26.1 ± 19.5
|
0.39
|
Initial presentation of septic shock
|
36 (11.0)
|
35 (20.3)
|
0.007
|
Requirement of intensive care
|
61 (18.7)
|
33 (19.2)
|
0.90
|
Appropriate antimicrobial therapy
|
|
|
|
Empirical
|
267 (81.7)
|
52 (30.2)
|
<0.001
|
Definitive
|
307 (93.9)
|
138 (80.2)
|
<0.001
|
Outcomes
|
|
|
|
Length of hospitalization, days, mean ± SD
|
20.2 ± 58.1
|
26.9 ± 41.3
|
0.15
|
In-hospital crude mortality
|
37 (11.3)
|
36 (20.9)
|
0.005
|
SD = standard deviation.
* Data are given as number (percent), unless otherwise specified. Boldface indicates statistical significance under the univariate analysis, i.e., a P value of <0.05.