The incidence and prognosis of patients with bacteremia.

Bacteremia is associated with increased morbidity and mortality, and ranks among the top seven causes of death in Europe and North America. The occurrence of bacteremia has increased for decades while short-term prognosis has remained unchanged or improved only slightly. Consequently, we are facing an increased number of bacteremia survivors for whom we know little about long-term survival and causes of death. Contemporary knowledge on the epidemiology and outcome of bacteremia is important to assess its impact on public health and is a prerequisite for any effective prevention and improvement of prognosis. This thesis is based on data from a bacteremia database (The Danish Observational Registry of Infectious Syndromes) comprising all bacteremias in Funen County, Denmark, between May 1999 and December 2008. Data on bacteremias were cross-linked with various administrative and research healthcare registries and we conducted 3 studies on adult bacteremia patients with the aims: to investigate the occurrence of and trends in first-time bacteremia and distribution of microorganisms in the general population; overall and by place of acquisition (study I), to investigate the overall and daily incidences of bacteremia among hospitalized patients (study II), to investigate and compare long-term mortality and causes of death after bacteremia with the general population (study III). Study I: In a population-based observational study, we identified 7786 residents of Funen County with first-time bacteremia for an overall incidence rate of 215.7 per 100,000 person years including 99.0 for community-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. The overall incidence rate decreased by 23.3% (95% CI, 17.8%-28.4%) from year 2000 to 2008 (3.3% per year, p<.001) due to decreasing rates of community-acquired bacteremia (3.7% per year, p < <0.001) and nosocomial bacteremia (4.2% per year, p<0.001). The incidence rate of healthcare-associated bacteremia remained more or less stable throughout the study period (p=0.17). The crude incidence rates decreased for Escherichia coli, Staphylococcus aureus, co-agulase-negative staphylococci and Streptococcus pneumoniae, and increased for Pseudomonas aeruginosa and enterococci species (p<0.05 for all the mentioned microorganisms). Regard-less of place of acquisition, the proportion of bacteremias caused by coagulase-negative staphylococci decreased while the proportion caused by Enterococcus species increased. Study II: In a multicenter hospital-based cohort study, we included 276,586 adult patients with 724,339 admissions to hospitals in Funen County for a total of 4,531,744 bed days. Among the hospitalized patients, we identified 10,281 first-time bacteremias per admission for an overall incidence of 14.2 per 1000 admissions and 23.6 per 10,000 bed days; highest for males, elderly individuals (> 65 years), and patients initially admitted to the Departments of Hematology, Nephrology, Internal Medicine, Urology or Oncology. The daily incidence was highest on the day of admission and declined rapidly to a low level on Day 3-7. Hereafter it increased steadily until Day 12 followed by more or less constant daily incidences. The daily incidences varied considerably with patient and clinical characteristics. Study III: In a population-based cohort study, we included 7783 patients with first-time bacteremia and 38,906 population controls matched on sex, year of birth and residency. We found that the cumulative mortality in bacteremia patients and population controls was 22.0% vs. 0.2% (30 days), 41.4% vs. 2.6% (1 year), and 75.8% vs. 36.6% (10 years). Bacteremia patients were consistently at increased risk of death compared with population controls throughout 12 years of follow-up and the risk of death remained 2-fold increased even among 5-year survivors of bacteremia (adjusted MRR: 2.1; 95% CI: 1.8-2.3). The most common causes of death after bacteremia were cancer and cardiovascular diseases. Compared with population controls, bacteremia patients were at the highest risk of death from genitourinary diseases and infectious diseases within 1 year of bacteremia. Among 1-year survivors of bacteremia, the risk of death was increased for all major causes of death compared with population controls. We conclude that the occurrence of bacteremia is decreasing in the general population. However, bacteremia is associated with a very poor short- and long-term prognosis and the risk of death remains increased for years compared with the general population. The most common causes of death after bacteremia are cancer and cardiovascular diseases. Among hospitalized patients, the incidence of bacteremia is highest within days of admission and varies with patient and clinical characteristics.