Community-acquired Staphylococcus aureus bacteremia: Studies of risk and prognosis with special attention to diabetes mellitus and chronic heart failure.

Community-acquired Staphylococcus aureus bacteremia (CA-SAB) is a serious infection with detrimental clinical effects. Chronic diseases constitute some of the most important risk and prognostic factors for CA-SAB. The prevalence of diabetes and chronic heart failure (CHF) is rapidly increasing on a global scale, nevertheless, there are few data available specifically elucidating the influence of these chronic conditions on CA-SAB risk and outcome. Therefore, to extend the current knowledge, we aimed to I) elucidate the impact of different definitions of healthcare-associated (HCA) infection on the prevalence of HCA-SAB, patient characteristics, and mortality, II) to investigate whether diabetes is a risk factor for CA-SAB, III) to ascertain the prognostic influence of diabetes on CA-SAB outcome, and IV) to investigate the influence of CHF on mortality in patients with CA-SAB. The thesis is based on a cross-sectional study, a case-control study, and two cohort studies, all conducted in Northern Denmark, 2000-2011. Utilizing the unique civil registration number assigned to all Danish residents, we linked data from the local departments of clinical microbiology, the Danish Civil Registration System, the Danish National Patient Registry, the LABKA database, and the Aarhus University Prescription Database. In study I, we included 4,385 patients with SAB. The proportion of patients classified as HCA-SAB ranged between 29.8% and 71.7% across five different definitions of HCA infection. Use of different definition of HCA infection also influenced the distribution of patient characteristics, whereas estimates of 30-day mortality remained unchanged (~ 24%). Study II included 2,638 patients with CA-SAB and 26,379 population controls matched by age, gender, and residence. We found diabetes to be strongly associated with an increased risk of CA-SAB (adjusted odds ratio=2.8 (95% CI, 2.5-3.1)). Compared with persons without diabetes, the increased CA-SAB risk was most apparent among patients with type 1 diabetes, patients with a long diabetes history, patients with poor glycemic control, and patients with diabetes complications. In study III, we included 2,638 patients with CA-SAB, of whom 713 (27.0%) had diabetes. After adjustment for potential confounders, the mortality rate ratio for patients with diabetes was 1.01 (95% CI, 0.84-1.20) after 30 days of follow-up. No notable differences in 30-day mortality were observed among patients with and without recent healthcare contacts, and the finding remained robust according to gender, age, comorbidity level, and characteristics of patients with diabetes (e.g. diabetes type and duration of diabetes). In study IV, CHF was associated with a 24% increase in 90-day mortality in patients with CA-SAB. The excess risk of death associated with CHF was most pronounced among patients with concomitant valvular disease and patients using very high doses of loop diuretics, as compared to patient without CHF. In conclusion, we observed considerable variation in the proportion of patients classified as HCA-SAB when different definitions of HCA infection were applied. Diabetes was associated with a substantially increased risk of CA-SAB, whereas CA-SAB outcome was virtually unaffected by diabetes. In contrast, patients with CHF experienced increased 90-day mortality compared with patients without CHF.