Study design
This single-center, ambidirectional cohort study proceeded at the ED of a university hospital in Japan between August 1, 2018 and August 31, 2019. The hospital is an 882-bed university teaching hospital with 8,000 adults presenting to the ED annually. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines were used to design and report the results from this study.10
Ethics and Consent to Participate
The Institutional Review Board (IRB) at Osaka Medical College approved the study protocol (No. 675(2476)) and waived the need for written, informed consent. All investigations were carried out in accordance with relevant guidelines and regulations. The need for consent was waived by an IRB.
Patients
This study included 548 consecutive patients ≥ 20 years old from whom blood was sampled in the ED. Inclusion criteria were: age ≥ 20 years; and at least one pair of blood cultures collected in the ED. Patients were excluded if all blood samples were collected elsewhere. If one pair of blood samples was collected at our ED and another was collected elsewhere or no second pair was collected, then only the pair collected at our ED was analyzed. One or more of the following comorbidities of patients were recorded: malignancy, diabetes mellitus, hypertension, prior stroke, dementia, chronic renal insufficiency, liver cirrhosis and coronary artery disease.11,12,13,14
Death data were also analyzed in February 2021.
Blood cultures
Nurses and other medical staff at our institution are not permitted to collect blood for cultures. Only physicians, typically first- or second-year interns, are permitted to collect blood samples for blood culture in the ED.
Blood (14–20 mL) from peripheral veins or arteries was sampled for aerobic and anaerobic cultures (7–10 mL each) in BacT/Alert FA Plus and FN Plus resin bottles (bioMérieux Inc., Durham, NC, USA). Physicians selected the topical disinfectant such as 1% ACHX, 10% PVI, alcohol and others available in the ED, according to their personal preferences. A blood culture was considered contaminated if one or more of the following organisms were identified in one of the two blood cultures: coagulase-negative staphylococci (CoNS), Propionibacterium acnes, Micrococci, Corynebacteria, Bacillus species other than Bacillus anthracis, or Clostridium perfringens.7,15,16 Viridans group streptococci are regarded as contaminants based on the described criteria,7,15 but are not considered as contaminants in our institute. Polymicrobial cultures showing a mixture of contaminant and true pathogens were regarded as contaminated.14 A culture was defined as “negative” when bacterial growth was absent or when a bacterium was regarded by the attending microbiologist as having low pathogenicity. The source of infection was identified based on chart review with other cultures such as sputum, urine, ascites and so on, or with other modalities including ultrasonography, X-ray, computed tomography (CT), and magnetic resonance imaging (MRI). Details are described in Table 1.
Table 1
Characteristics of patients with blood cultures in the emergency department.
Characteristics of patients | True bacteremia | Contamination | True negative | P |
n = 114 | n = 110 | n = 324 |
Mean age, y (SD) | 72.6 | (11.8) | 74.3 | (11.4) | 67.3 | (16.7) | < 0.001 |
Male sex, n (%) | 64 | (56.1) | 75 | (68.2) | 189 | (58.3) | 0.126 |
Major comorbidities, n (%) | | | | | | |
Malignancy | 50 | (43.9) | 40 | (36.4) | 124 | (38.4) | 0.473 |
Diabetes mellitus | 26 | (22.8) | 25 | (22.7) | 58 | (18.0) | 0.383 |
Hypertension | 41 | (36.0) | 43 | (39.1) | 80 | (24.8) | 0.005 |
Previous stroke | 10 | (8.8) | 9 | (8.2) | 24 | (7.4) | 0.888 |
Chronic renal insufficiency | 14 | (12.3) | 7 | (6.4) | 29 | (9.0) | 0.302 |
Liver cirrhosis | 5 | (4.4) | 1 | (0.9) | 9 | (2.8) | 0.288* |
Coronary artery disease | 10 | (8.8) | 9 | (8.2) | 19 | (5.9) | 0.488 |
Dementia | 7 | (6.1) | 13 | (11.8) | 21 | (6.5) | 0.153 |
Quick SOFA, n (%) | | | | | | 0.087 |
0 | 37 | (32.5) | 40 | (36.4) | 125 | (38.6) | |
1 | 33 | (29.0) | 41 | (37.3) | 114 | (35.2) | |
2 | 35 | (30.7) | 23 | (20.9) | 77 | (23.8) | |
3 | 9 | (7.9) | 6 | (5.5) | 8 | (2.5) | |
Origin of infection, n (%) | | | | | | |
Central nervous system | 1 | (0.9) | 0 | 0.0 | 3 | (0.9) | 0.823* |
Pulmonary | 12 | (10.5) | 41 | (37.3) | 94 | (29.0) | < 0.001 |
Cardiovascular system | 6 | (5.3) | 0 | 0.0 | 2 | (0.6) | 0.003* |
Abdomen | 19 | (16.7) | 12 | (10.9) | 35 | (10.8) | 0.234 |
Urinary tract | 47 | (41.2) | 13 | (11.8) | 53 | (16.4) | < 0.001 |
Skin | 6 | (5.3) | 9 | (8.2) | 9 | (2.8) | 0.283 |
Other or unknown | 26 | (22.8) | 39 | (35.5) | 137 | (42.3) | 0.001 |
Death | 37 | (32.5) | 35 | (31.8) | 99 | (30.6) | 0.92 |
Death within 30 days | 11 | (9.7) | 5 | (4.6) | 34 | (10.5) | 0.169 |
SD, standard deviation; SOFA, sequential organ failure assessment |
* Fisher’s exact test was performed because of small numbers of patients in several cells. Other comparisons were analyzed using the χ2 test and one-way analysis of variance. |
Origin of infection means the cause of infection according to a medical chart review with several cultures and with diagnostic modalities. |
Central nervous system includes meningitis, encephalitis and brain abscess. Pulmonary includes pneumonia, bronchitis, pleuritis and upper respiratory infection. Cardiovascular system includes endocarditis and pericarditis. Abdomen includes cholangitis, gastroenteritis, cancer of the gastrointestinal tract, hepatitis, cholecystitis, appendicitis and pancreatitis. Urinary tract includes pyelonephritis, cystitis and prostatitis. Skin includes decubitus, cellulitis, impetigo and erysipelas. Other or unknown includes febrile neutropenia, and cases where the source of infection cannot be identified. |
Statistical analysis
Categorical variables are described as frequencies and percentages (%) and continuous variables are shown as mean with standard deviation (SD). Data were compared using one-way analysis of variance, the χ2 test and Fisher’s exact test, as appropriate. Differences in risk and robust 95% confidence intervals (CIs) of contamination according to sites and topical disinfectants were estimated using uni- and multivariate analyses with modified least-squares regression and a robust standard error estimator.1718 The same patients were considered as a random effect in the above model. Age, sex and disease status were adjusted as confounders in multivariate analyses. Because blood can be sampled from few sites, we also included blood in five categories: CV catheter, blood sampled from a newly inserted central venous (CV) catheter; Femoral, blood sampled from the femoral artery or vein; Other, blood sampled from a newly inserted arterial catheter and implanted port; Venous, blood sampled from venipuncture without catheter insertion; and Venous catheter, blood sampled from a newly inserted venous catheter. Because we did not have many topical disinfectants to assess, we included only PVI, ACHX and Other types (alcohol and benzalkonium) in analyses. We did not impute missing values. For all statistical investigations, values of P < 0.05 were taken as significant. All analyses were performed using STATA version 16.1 (Stata Corp., College Station, TX, USA).