The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections

Adult patients (≥ 18 years old) admitted to one of two teaching hospital between January 2019 and December 2019 were enrolled. The participating institutions were Samsung Changwon Hospital and Inje University Busan Paik Hospital located in Changwon and Busan, Korea, respectively. Electronic medical records were reviewed to collect data of laboratory results and clinical characteristics of patients.

We defined BSIs contributing mortality as a BSI within the 2-weeks before death, as prior studies have used a 14-day mortality to represent short-term mortality from BSI [8]. The results of blood cultures performed on the study population during the 2-weeks before death were collected. When bacteria or fungi were isolated from more than two separate blood samples or from a single blood sample in patients with explainable clinical symptoms and focuses other than skin commensals, they were considered as true BSIs [13]. We only considered isolated pathogens from true BSI as the pathogens contributing to mortality.

Patients and their isolated pathogens were classified by their acquisition sites: Community-acquired (CA)-, healthcare-associated (HCA)- and HA-BSI. HCA infection was defined as infected patients with at least one of the four elements: (1) Parenteral treatment within 30 days, (2) outpatient chemotherapy or hemodialysis within 30 days, (3) hospitalization for ≥ 2 days in the preceding 90 days and (4) nursing home residence [14]. To compare baseline characteristics of patients and pathogens in CA-, HCA-, and HA-BSI groups, the following data were collected: age, sex, underlying disease, prior major surgery (within 4 weeks), prior antibiotics use (within 4 weeks), infection focus of BSI, and appropriateness of empirical antimicrobial treatment. Appropriate empirical antibiotic use was defined when agents to which the microbes were susceptible were administered within 48 h after obtaining the blood culture sample. In addition, the antimicrobial susceptibility of each pathogen was classified into four major resistance patterns: cefotaxime-resistant Enterobacteriaceae (not including carbapenem-resistant), carbapenem-resistant GNB (CRGNB), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). Stenotrophomonas maltophilia, which has intrinsic resistance to carbapenem, was also classified as CRGNB [15]. In addition, difficult-to-treat resistance (DTR), defined as nonsusceptibility to all β-lactams and fluoroquinolones tested, was identified among CRGNB [16, 17].

Blood was taken via a peripheral vein and/or a central line. Blood was drawn for two sets of blood culture bottles (aerobic and anaerobic, 8-10 cc blood for each bottle), and culture bottles were incubated in the Bactec-9240 system (Becton Dickinson, Sparks, MD) or BacT/Alert 3D system (bioMérieux Inc., Marcy l’Etoile, France).). All samples were cultured in blood agar and MacConkey agar plates in a 35 °C incubator for 24 h and identified using the Vitek MS system (BioMérieux, Hazelwood, MI, USA). All antimicrobial susceptibility tests (ASTs) were performed using A Vitek II automated system (bioMérieux Inc.) according to the Clinical and Laboratory Standards Institute 2018 guidelines [18]. All procedures were performed according to the manufacturer’s instructions.

During the study period, a total of 1849 patients died. There were 331 patients with positive blood culture during the 2-weeks prior to death. After excluding two patients under 18 years of age and 49 patients with contaminated blood cultures, 280 (15.1%) patients were included in this study. The mean age of the study population was 69.92 years, and the ratio of males to females was 3:2. Seventy-one (25.4%), 53 (18.9%), and 156 (55.7%) patients were classified as CA-, HCA- and HA-BSI acquired infection, respectively. Whereas liver disease was more frequently observed in the CA-BSI group, cardiovascular disease was more frequently observed in the HA-BSI group. Malignancy and prior antibiotic use were more frequently observed in HCA- and HA-BSI groups than in the CA-BSI group (Table 1).

A total of 316 pathogens were isolated from blood culture, and 74 (23.4%), 58 (18.4%) and 184 (58.2%) pathogens were identified from the CA-, HCA- and HA-BSI groups, respectively. Of the 280 patients, 34 patients experienced polymicrobial BSI in single BSI event or more than 2 consecutive BSI events, of which the HA-BSI group accounted for ~ 75% (26/34).

The five most common pathogens were Klebsiella pneumonia (17.1%), Escherichia coli (16.4%), Staphylococcus aureus (11.4%), Acinetobacter baumannii (10.8%), and Candida species (9.2%). The commonest pathogen in CA-, HCA-, and HA-BSI groups were E. coli, K. pneumoniae and A. baumannii (Table 2). Common isolated pathogens from each hospital were relatively similar and are described in Additional file 1: Tables S1 and S2. No difference in patient age was observed among the pathogen groups (Additional file 1: Table S3).

Overall, 54.5% (85/156) of patients in the HA-BSI group had a central venous catheter, and 37.2% (58/156) of patients were admitted to the intensive care unit when BSI occurred (not shown in Table). In addition, 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The most commonly isolated pathogen during carbapenem therapy was A. baumannii (Additional file 1: Table S4).

Figure 1 shows the characteristics of each BSI group. Almost all of the fungi were isolated from the HA-BSI group. Candida species comprised 96.6% (28/29) of fungi isolates, and C. albicans was the most predominant (17 cases of 28 Candida species) (Fig. 1A). Meanwhile, the most common portal of BSI entry was primary or from an unknown focus. Central venous catheter-related infection was more frequently observed in the HA-BSI group (28.3%) than in the HCA-BSI group (3.4%) or the CA-BSI group (0%) (Fig. 1B).

The most frequently observed drug resistance was cefotaxime-resistant Enterobacteriaceae, which was distributed relatively evenly amongst in the CA-BSI (21.6%), HCA-BSI (20.6%), and HA-BSI groups (17.9%). There was no significant difference in the VRE and MRSA proportions in the three BSI groups. However, CR-GNB was the predominant drug resistant pathogen in the HA-BSI group (21.9%) (Fig. 1C). The DTR pattern was identified in 81.8% (36/44) of CRGNBs. The most common species of CRGNB was A. baumannii (24 isolates), which rarely or never contributed to mortality in HCA- (6.9%) or CA-BSIs (0%). Inappropriate empirical antimicrobial treatment was more frequently observed in HA-BSIs (51.9%) compared with HCA- (37.7%) and CA-BSIs (21.1%) (Fig. 1D). In our study population, 65 cases of BSI were empirically treated with type 2 carbapenems and glycopeptides. However, the treatment was still inappropriate in 26.2% of these patients due to drug resistance (data not shown).