Bloodstream infections in Finland with particular focus on early death

Bloodstream infections (BSI) are a major global health burden. Mortality of BSI has remained high despite advances in antimicrobial therapy and intensive care. A notable proportion, up to one third of BSI-associated deaths occur early, already within 2 days after the first positive blood culture specimen. Overall, limited population-based data are available regarding the incidence and outcome of BSIs, as well as the timing of death and factors related to early fatal outcome. The aims of the study were to analyze patient characteristics, causative pathogens, and accuracy of treatment of BSIs leading to early death and to assess the effect of comorbidity, underlying factors, and microbial etiology on the outcome and timing of death of both community-acquired BSIs (CA-BSI) and healthcare-associated BSIs (HA-BSI), and of nosocomial BSIs. In addition, nationwide temporal trends in the incidence, mortality and causative agents of BSIs were explored. For studies I, III and IV, BSIs were identified from the National Infectious Diseases Register. Data on death within 2 days (i.e., early death) and 1 month after the positive blood culture were gathered from the Population Information System (Studies I–IV). Study I included all patients with BSI residing in the Hospital District of Helsinki and Uusimaa in 2007 who died within 2 days of the blood culture specimen. Study II consisted of nosocomial BSIs reported by hospitals taking part in national surveillance in Finland during 1999–2014. Studies III and IV comprised all BSIs in Finland during 2004–2018. Data on the origin of BSI and patients’ underlying diseases were gathered from the National Hospital Discharge Register. In study I, Streptococcus pneumoniae (29%) and Escherichia coli (24%) were the most common causative microbes of CA-BSIs leading to early death, while Pseudomonas aeruginosa (24%) and Staphylococcus aureus (18%) among HA-BSIs. Initial antimicrobial treatment was more often inappropriate in HA-BSIs leading to early death compared to CA-BSIs (50% vs. 12%). Treatment delays tended to be longer in CA-BSIs. In total, 17,767 nosocomial BSIs were identified of which 3% were fatal within 2 days and 14% within 1 month (Study II). Of the fatal nosocomial BSIs, 23% led to early death. The patients who died early were older and their BSIs were more frequently caused by gram-negative bacteria (39% vs. 27%) and related to intensive care, as compared to those who were alive at 1 month. In study III, 173,715 BSIs were identified in the nationwide surveillance of BSIs during 2004–2018. The annual incidence rose from 150 to 309 BSI episodes/100,000 population, and the rise was most prominent in the elderly. The 1-month case fatality declined slightly, from 13.0% to 12.6%, while the all-cause mortality increased from 20 to 39 deaths/100,000. The proportion of E. coli BSIs of all BSIs rose from 26% to 30% and those caused by multidrug-resistant microbes from 0.4% to 2.8%, mostly due to a rise in extended-spectrum β-lactamase-producing E. coli. An increase from 67% to 78% was observed in the proportion of CA-BSIs and from 14% to 23% in patients with severe comorbidity. Of all BSIs, 13% were fatal within 1 month and of these fatal episodes, 28% occurred early (Study IV). The 2-day and 1-month case fatalities of HA-BSIs (5.4% and 21%) were higher compared to those of CA-BSIs (3.0% and 9.8%). Compared to BSI patients who were alive at day 3, those who died early were older and had more severe underlying comorbidities. Furthermore, BSIs leading to early death were more often polymicrobial (12% vs. 6.3%) and caused by P. aeruginosa (6.2% vs. 2.0%), fungi (2.9% vs. 1.4%) and multi-drug resistant (MDR) microbes (2.2% vs. 1.8%), compared to other BSIs. In conclusion, the incidence and mortality of BSIs increased considerably in Finland over time. Despite a rising proportion of aged and comorbid patients, the case fatality of BSIs did not increase possibly reflecting advancements in recognition and treatment of BSIs. The rising trend in CA-BSIs and in resistance of E. coli causes concern and calls for preventive measures and guidance of antimicrobial therapy. Nearly 30% of BSI-associated deaths occurred early. Polymicrobial, fungal, P. aeruginosa and MDR etiology were overrepresented among BSIs with early fatal outcome. These causative agents are a challenge for clinicians with respect to the choice of empiric antimicrobial regimen. The findings underline the importance of preventive interventions and prompt identification of infection and initiation of effective antimicrobial treatment according to the origin of infection and local resistance pattern.