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Objectives: Patients with bacteremia have a high mortality and generally require urgent treatment. The authors conducted a study to describe bacteremic patients in emergency departments (EDs) and to identify risk factors for mortality.
Methods: Bacteremic patients in EDs were identified retrospectively at a university hospital from January 2007 to December 2007. Demographic characteristics, underlying illness, clinical conditions, microbiology, and the source of bacteremia were collected and analyzed for their association with 28-day mortality.
Results: During the study period, 621 cases (50.2% male) were included, with a mean (±SD) age of 62.8 (±17.4) years. The most common underlying disease was diabetes mellitus (39.3%). Escherichia coli (39.2%) was the most frequently isolated pathogen. The most common source of bacteremia was urinary tract infection (41.2%), followed by primary bacteremia (13.2%). The overall 28-day mortality rate was 12.6%. Multivariate stepwise logistic regression analysis showed age > 60 years (odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.29 to 4.92, p = 0.007), malignancy (OR = 2.66, 95% CI = 1.44 to 4.91, p = 0.002), liver cirrhosis (OR = 2.08, 95% CI = 1.02 to 4.26, p = 0.044), alcohol use (OR = 5.73, 95% CI = 2.10 to 15.63, p = 0.001), polymicrobial bacteremia (OR = 3.99, 95% CI = 1.75 to 9.10, p = 0.001), anemia (OR = 2.33, 95% CI = 1.34 to 4.03, p = 0.003), and sepsis (OR = 1.94, 95% CI = 1.16 to 3.37, p = 0.019) were independent risk factors for 28-day mortality.
Conclusions: Bacteremic patients in the ED have a high mortality, particularly with these risk factors. It is important for physicians to recognize the factors that potentially contribute to mortality of bacteremic patients in the ED.
Fever is one of the leading reasons for visiting emergency departments (EDs), and it is the chief complaint at 5% of all visits in the United States.1 Blood culture is an important diagnostic tool to evaluate certain febrile patients in the ED. It is estimated that blood cultures are ordered in 2.8% of all ED visits, and about 3.1 million blood cultures are ordered annually in U.S. EDs.1 Although indications for the use of blood cultures are available,2,3 there are no generally acceptable guidelines for blood culture for patients with sepsis in the ED.
Patients who present with bacteremia in the ED have a high mortality and generally require urgent admission for further treatment with antimicrobial agents.4 Therefore, identification of bacteremic patients at risk for mortality is a critical issue in the ED. Furthermore, to guide empirical antimicrobial treatment, recognizing the most common pathogens responsible for bacteremia and the most frequent sites of infection causing bacteremia are crucial. However, few studies discuss the manifestations of bacteremia in the ED or evaluate the risk factors for their mortality.5,6 Therefore, we performed this study with the following objectives: 1) describe the clinical characteristics, 2) identify the most frequently isolated microorganisms, 3) define the most common sources of bacteremia, 4) describe survival rates, and 5) determine the independent predictive factors for the 28-day mortality of bacteremic patients in the ED.
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During the study period, there were 2,554 positive blood cultures among 62,715 ED visits. After excluding mycobacteria, fungi, contamination, and identical pathogens, 678 pathogens were isolated in 634 case episodes. Thirteen case episodes (2.1%) were lost to follow-up. A total of 664 pathogens isolated in 621 case episodes were included in our study. There were 312 males (50.2%) and 309 females (49.8%), with a mean ± SD age of 62.8 ± 17.4 years (range = 18–96 years). Diabetes mellitus was found in 39.3% of patients, followed by hypertension, malignancy, and liver cirrhosis (Table 1). Patients were found to have polymicrobial bacteremia in 6.3% of cases and to have Gram-negative bacteremia in 23.3%.
Table 1. Demographic Characteristics, Underlying Illnesses, and Clinical Conditions of 621 Bacteremic Case Episodes in the ED
|Age (yr), mean ± SD||62.8 ± 17.3|
|Sex, male||312 (50.2)|
| Diabetes mellitus||244 (39.3)|
| End-stage renal disease||28 (4.5)|
| Malignancy||124 (20.0)|
| Liver cirrhosis||87 (14.0)|
| Autoimmune disease||10 (1.6)|
| HIV infection||5 (0.8)|
| COPD||25 (4.0)|
| Coronary artery disease||20 (3.2)|
| Hypertension||226 (36.4)|
| Congestive heart failure||38 (6.1)|
| Immunosuppressant therapy||39 (6.3)|
| Intravenous drug abuse||17 (2.7)|
| Cerebrovascular event||71 (11.4)|
| Bedsore||19 (3.1)|
| Alcohol use||44 (7.1)|
| Monomicrobial bacteremia||582 (93.7)|
| Polymicrobial bacteremia||39 (6.3)|
| Gram-positive bacteremia*||155 (23.3)|
| Gram-negative bacteremia*||509 (76.7)|
| Anemia†||167 (26.9)|
| Neutropenia‡§||9 (1.5)|
| Thrombocytopenia¶||147 (23.7)|
| Sepsis||225 (36.2)|
Univariate analysis of risk factors for 28-day mortality is shown in Table 2. There were no significant differences in mortality by age or sex. However, mortality rates were different in the presence versus absence of malignancy, liver cirrhosis, immunosuppressant therapy, alcohol use, polymicrobial bacteremia, anemia, thrombocytopenia, and sepsis.
Table 2. Demographic Characteristics, Underlying Illnesses, and Clinical Conditions for 28-day Mortality of 621 Bacteremic Case Episodes in the ED
|Factors||28-day Mortality||OR (95% CI)||p-value|
|With Factor||Without Factor|
|Age > 60 yr||49/367 (13.4)||29/254 (11.4)||1.20 (0.73–1.95)||0.475|
|Sex, male||47/312 (15.1)||31/309 (10.0)||1.59 (0.98–2.58)||0.059|
| Diabetes mellitus||27/244 (11.1)||51/377 (13.5)||0.80 (0.48–1.31)||0.366|
| End-stage renal disease||4/28 (14.3)||74/593 (12.5)||1.17 (0.40–3.46)||0.769|
| Malignancy||28/124 (22.6)||50/497 (10.1)||2.61 (1.56–4.35)||<0.001|
| Liver cirrhosis||28/87 (32.2)||50/534 (9.4)||4.59 (2.69–7.85)||<0.001|
| Autoimmune disease||2/10 (20.0)||76/611 (12.4)||1.76 (0.37–8.44)||0.364|
| HIV infection||1/5 (20.0)||77/616 (12.5)||1.75 (0.19–15.86)||0.490|
| COPD||5/25 (20.0)||73/596 (12.2)||1.79 (0.65–4.92)||0.227|
| Immunosuppressant therapy||10/39 (25.6)||68/582 (11.7)||2.61 (1.22–5.58)||0.021|
| Alcohol use||17/44 (38.6)||61/577 (10.6)||5.33 (2.75–10.33)||<0.001|
| Polymicrobial bacteremia||13/39 (33.3)||65/582 (11.2)||3.98 (1.95–8.12)||<0.001|
| Anemia*||36/167 (21.6)||42/454 (9.3)||2.70 (1.66–4.39)||<0.001|
| Neutropenia†‡||3/9 (33.3)||72/603 (11.9)||3.69 (0.90–15.07)||0.086|
| Thrombocytopenia§||37/147 (25.2)||41/474 (8.6)||3.55 (2.17–5.81)||<0.001|
| Sepsis||39/225 (17.3)||39/396 (9.8)||1.92 (1.19–3.10)||0.007|
Figures 1 and 2 show the sources and species of bacteremia, respectively. The most common source of bacteremia was urinary tract infection, and the most frequent isolate was Escherichia coli. Patients with liver abscess, urinary tract infection, and bone or joint infection had the lowest mortality rates (3.7, 4.7, and 4.8%, respectively), and patients with respiratory tract infection (40.4%) and intraabdominal infection (44.1%) had the highest mortality rates. The ORs for mortality regarding different sources of bacteremia are shown in Table 3. There was no significant difference in mortality rate between Gram-positive and Gram-negative bacteremia (p = 0.727; Table 4). No significant differences were discovered among the Gram-positive pathogens. However, a statistically higher 28-day mortality rate was discovered in patients with Klebsiella spp., Pseudomonas spp., and Aeromonas spp. bacteremia when compared with E. coli.
Figure 1. Sources of infection among bacteremic patients in the ED. UTI = urinary tract infection; SSTI = skin and soft tissue infection; LRI = lower respiratory tract infection; BTI = biliary tract infection; ENT = ear, nose and throat; CNS = central nervous system.
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Figure 2. Isolated pathogens (n=664) of bacteremic ED patients. (a) ESBL-producing E. coli, 12/260 (4.6%); (b) ESBL-producing K. pneumoniae, 3/115 (2.6%); (c) oxacillin-resistant S. aureus (ORSA), 29/77 (37.7%); (d) ESBL-producing P. mirabilis, 2/19 (10.5%). ESBL = extended-spectrum β-lactamase.
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Table 3. Sites of Infection Associated with 28-day Mortality Among 621 Bacteremic Case Episodes in the ED
|Sites of Infection||Mortality (%)||OR (95% CI)||p-value|
|Urinary tract||12/256 (4.7)||1 (reference)|| |
|Lower respiratory tract||21/52 (40.4)||13.77 (6.18–30.71)||<0.001|
|Biliary tract||4/51 (7.8)||1.73 (0.54–5.60)||0.360|
|Skin and soft tissue||7/58 (12.1)||2.79 (1.05–7.43)||0.040|
|Intraabdomen||15/34 (44.1)||16.05 (6.59–39.14)||<0.001|
|Bone/joint||1/21 (4.8)||1.02 (0.13–8.22)||0.988|
|Liver abscess||1/27 (3.7)||0.78 (0.10–6.26)||0.817|
|Infective endocarditis||1/15 (6.7)||1.45 (0.18–11.98)||0.729|
|Catheter-related||2/12 (16.7)||4.07 (0.80–20.65)||0.091|
|Central nervous system||0/3 (0)||—|| —|
|Ear, nose, throat/mouth||0/5 (0)||—|| —|
|Intravascular infection||1/5 (20.0)||5.08 (0.53–49.04)||0.160|
|Primary bacteremia||13/82 (15.9)||3.83 (1.67–8.78)||0.001|
Table 4. Pathogens Associated with 28-day Mortality Among 582 Case Episodes With Monomicrobial Bacteremia in the ED
|Pathogens||Mortality (%)||OR (95% CI)||p-value|
|Gram-positive*||17/142 (12.0)||1.11 (0.62–2.00)||0.727|
| Staphylococcus spp.||10/77 (13.0)||1 (reference)||—|
| Streptococcus spp.||6/55 (10.9)||0.82 (0.28–2.41)||0.719|
| Enterococcus spp.||0/7 (0)||—||—|
| Others||1/3 (33.3)||—||—|
|Gram-negative||48/440 (10.9)|| || |
| Escherichia coli||15/235 (6.4)||1 (reference)||—|
| Klebsiella spp.||14/96 (14.6)||2.50 (1.16–5.42)||0.020|
| Pseudomonas spp.||4/19 (21.1)||3.91 (1.15–13.26)||0.029|
| Proteus mirabilis||0/15 (0)||—||—|
| Enterobacter spp.||1/12 (8.3)||1.33 (0.16–11.03)||0.790|
| Aeromonas spp.||3/12 (25.0)||4.89 (1.20–19.97)||0.027|
| Salmonella spp.||1/10 (10.0)||1.63 (0.19–13.73)||0.653|
| Acinetobacter spp.||2/8 (25.0)||4.89 (0.91–26.33)||0.065|
| Citrobacter spp.||1/6 (16.7)||2.93 (0.32–26.74)||0.340|
The overall mortality rates of all bacteremic cases in the ED were as follows: 3-day mortality, 4.0%; 7-day mortality, 6.8%; 14-day mortality, 10.3%; 21-day mortality, 11.4%; and 28-day mortality, 12.6%. The Kaplan-Meier survival curve is shown in Figure 3. More than half of the deaths (53.8%) occurred during the first week after the onset of bacteremia.
We tested the demographic data, underlying illnesses, and clinical conditions to identify independent risks for the 28-day mortality in a multivariate stepwise logistic regression model and found that age > 60 years, malignancy, liver cirrhosis, alcohol use, polymicrobial bacteremia, anemia, and sepsis were independent predicting factors (Table 5).
Table 5. Multivariate Forward Stepwise Logistic Regression Model of Risk Factors for 28-day Mortality of Bacteremic Case Episodes in the ED*
|Factors||OR (95% CI)||p-value|
|Age > 60 yr||2.52 (1.29–4.92)||0.007|
|Liver cirrhosis||2.08 (1.02–4.26)||0.044|
|Alcohol use||5.73 (2.10–15.63)||0.001|
|Polymicrobial bacteremia||3.99 (1.75–9.10)||0.001|
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Although bacteremia is a critical condition in the ED, there are few studies discussing bacteremia in adults visiting EDs. Javaloyas et al.4 reported that Gram-negative bacteria accounted for 65.0% of community-acquired bacteremia, and E. coli was the most frequent isolate (45.0%). Recently, Groeneveld12 evaluated the risk factors for community-acquired infections in febrile medical patients. The most frequent source of bacteremia was the respiratory system, and Enterobacteriaceae (including E. coli) were the most frequent isolates. These findings are similar to those of our study. However, neither of these studies were ED population-based, and they did not thoroughly examine and analyze the underlying illness, microbiology, and prognosis of bacteremic patients.
Patients with underlying malignancy are in an immunocompromised state and easily infected by many microorganisms. Mortality appears to increase in cancer patients complicated with bacteremia, particularly when a clinical site of infection exists.13,14 Liver cirrhosis and chronic alcohol use are also known to be associated with impaired immunity. In both cases, patients are frequently infected with highly virulent pathogens and consequently experience increased morbidity and mortality.15,16 This defect in the immune system could explain the higher mortality rate in patients with these underlying diseases.
Polymicrobial infection is frequently found in immunocompromised patients or in intraabdominal and complicated soft tissue infection.14 As a combination of several antimicrobial agents is usually needed to treat patients with polymicrobial infections, it is important to recognize the risks for polymicrobial bacteremia. However, no comprehensive study has been performed to evaluate the risks for polymicrobial infection in the ED. Our study showed polymicrobial infection was an independent factor for mortality in bacteremic patients. Further study investigating polymicrobial bacteremia in the ED is necessary.
The lower respiratory tract is one of the most frequent infection-related causes of death.17 Probable pathogens were found in 5%–14% of pretreatment blood cultures in a large series of nonselected patients with community-acquired pneumonia.18 Patients with community-acquired pneumonia complicated with bacteremia were reported to have a higher mortality rate (27.6%) than those with no bacteremia (12.6%).19 Our study also showed high mortality rate (40.4%) in bacteremic patients with lower respiratory tract infection.
With respect to the bacteremia etiology, we observed a significantly lower mortality rate with E. coli bacteremia and a higher mortality rate with Klebsiella spp., Pseudomonas spp., and Aeromonas spp. bacteremia. This result is also similar to another study.12 Moreover, Pedersen et al.20 reported a 30-day mortality rate of 13% to 15% in patients with primary bacteremia. The incidence (13.2%) and the mortality rate (15.9%) of primary bacteremia in our study were close to those of this previous report.
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In this general survey of bacteremic patients in the ED, we found that old age, malignancy, liver cirrhosis, alcohol use, polymicrobial bacteremia, anemia, and sepsis were independent predicting factors for 28-day mortality in bacteremic ED patients. The mortality rate differed between patients with urinary tract infection and other sources of infections. We also found that patients with E. coli bacteremia had a lower mortality rate than did those with sepsis due to Klebsiella, Pseudomonas, and Aeromonas spp. It is important for physicians to recognize these factors that potentially contribute to mortality in bacteremic ED patients.