Background: Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs. Methods: We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device. Results: Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5–7.8). The lowest IE prevalence was found with Streptococcus pneumoniae ( S pneumoniae ) 1.2% (0.8–1.6) and Spyogenes 1.9% (0.9–3.3). An intermediary IE prevalence was found with Sanginosus 4.8% (3.0–7.3), Ssalivarius 5.8% (2.9–10.1), and Sagalactiae 9.1% (6.6–12.1). The highest IE prevalence was found with Smitis/oralis 19.4% (15.6–23.5), Sgallolyticus (formerly Sbovis ) 30.2% (24.3–36.7), Ssanguinis 34.6% (26.6–43.3), Sgordonii 44.2% (34.0–54.8), and Smutans 47.9% (33.3–62.8). In multivariable analysis using S pneumoniae as reference, all species except S pyogenes were associated with significantly higher IE risk, with the highest risk found with S gallolyticus odds ratio (OR) 31.0 (18.8–51.1), S mitis/oralis OR 31.6 (19.8–50.5), S sanguinis OR 59.1 (32.6–107), S gordonii OR 80.8 (43.9–149), and S mutans OR 81.3 (37.6–176). Conclusions: The prevalence of IE in streptococcal BSIs is species dependent with S mutans, S gordonii, S sanguinis, S gallolyticus , and S mitis/oralis having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.

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Background Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival and reduce complications, but the balance between benefit and harm is difficult and may be closely related to age and type of surgical intervention. We aimed to examine how age and type of left-sided surgical intervention modified mortality in patients undergoing surgery for IE. Methods By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment 2000–2017. Patients were grouped by age < 60 years, 60–75 years, and ≥ 75 years. Multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality. Results We included 1767 patients with IE undergoing surgery, 735 patients < 60 years (24.1% female), 766 patients 60–75 years (25.8% female), and 266 patients ≥75 years (36.1% female). The proportions of patients undergoing surgery were 35.3, 26.9, and 9.1% for patients < 60 years, 60–75 years, and > 75 years, respectively. Mortality at 90 days were 7.5, 13.9, and 22.3% (p < 0.001) for three age groups. In adjusted analyses, patients 60–75 years and patients ≥75 years were associated with a higher mortality, HR = 1.84 (95% CI: 1.48–2.29) and HR = 2.47 (95% CI: 1.88–3.24) as compared with patients < 60 years. Factors associated with 90-day mortality were: mitral valve surgery, a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, age, diabetes, and prosthetic heart valve implantation prior to IE admission. Conclusions In patients undergoing surgery for IE, mortality increased significantly with age and 1 in 5 died above age 75 years. Mitral valve surgery as well as multiple valve interventions augmented mortality further.

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Background Infective endocarditis (IE) is diagnosed in 7–8% of streptococcal bloodstream infections (BSIs), yet it is unclear when to perform transthoracic (TTE) and transoesophageal echocardiography (TOE) according to different streptococcal species. The aim of this sub-study was to propose a flowchart for the use of echocardiography in streptococcal BSIs. Methods In a population-based setup, we investigated all patients admitted with streptococcal BSIs and crosslinked data with nationwide registries to identify comorbidities and concomitant hospitalization with IE. Streptococcal species were divided in four groups based on the crude risk of being diagnosed with IE (low-risk < 3%, moderate-risk 3–10%, high-risk 10–30% and very high-risk > 30%). Based on number of positive blood culture (BC) bottles and IE risk factors (prosthetic valve, previous IE, native valve disease, and cardiac device), we further stratified cases according to probability of concomitant IE diagnosis to create a flowchart suggesting TTE plus TOE (IE > 10%), TTE (IE 3–10%), or “wait & see” (IE < 3%). Results We included 6393 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men). BSIs with low-risk streptococci (S. pneumoniae, S. pyogenes, S. intermedius) are not initially recommended echocardiography, unless they have ≥3 positive BC bottles and an IE risk factor. Moderate-risk streptococci (S. agalactiae, S. anginosus, S. constellatus, S. dysgalactiae, S. salivarius, S. thermophilus) are guided to “wait & see” strategy if they neither have a risk factor nor ≥3 positive BC bottles, while a TTE is recommended if they have either ≥3 positive BC bottles or a risk factor. Further, a TTE and TOE are recommended if they present with both. High-risk streptococci (S. mitis/oralis, S. parasanguinis, G. adiacens) are directed to a TTE if they neither have a risk factor nor ≥3 positive BC bottles, but to TTE and TOE if they have either ≥3 positive BC bottles or a risk factor. Very high-risk streptococci (S. gordonii, S. gallolyticus, S. mutans, S. sanguinis) are guided directly to TTE and TOE due to a high baseline IE prevalence. Conclusion In addition to the clinical picture, this flowchart based on streptococcal species, number of positive blood culture bottles, and risk factors, can help guide the use of echocardiography in streptococcal bloodstream infections. Since echocardiography results are not available the findings should be confirmed prospectively with the use of systematic echocardiography.

Background Streptococcal bloodstream infection (BSI) is a common cause of infective endocarditis (IE), yet prognostic factors for mortality are poorly investigated. Purpose To investigate risk factors associated with in-hospital and one-year mortality in streptococcal IE. Methods All patients with a streptococcal BSI, from 2008 to 2017, were included in a regional population-based setup. Based on microbiological identification of phylogenetic relationship, streptococcal species were classified into eight main subgroups: Anginosus, Bovis, Mitis, Mutans, Salivarius, Pyogenic, nutritionally variant streptococci, and S. pneumoniae. Data were crosslinked with nationwide registries for identification of demographics, concomitant hospitalization with IE, medical history, seasonal variation, and socioeconomic status. Patients were followed up until death or a maximum of 365 days after admittance, whichever came first. Using a multivariable adjusted Cox proportional hazard analysis, independent risk factors associated with in-hospital and one-year mortality were identified. Results Among 6,224 patients with a streptococcal BSI, 435 (7.0%) patients with streptococcal IE (mean age 69.0 (SD 14.8), 66% men) were included. The in-hospital mortality in IE patients was 11% (n=48), while the one-year mortality was 23% (n=100). Patients infected with species from the Bovis group had the lowest crude one-year mortality (13%), while patients infected with the Salivarius group had the highest crude mortality (36%). The proportion of deaths among women with IE were significantly higher than among men, both in-hospital (15% versus 9%, p=0.04) and after one year (29% versus 20%, p=0.02). Further, patients dying within one year had a significantly higher prevalence of ischemic heart disease (IHD) (p=0.02), congestive heart failure (CHF) (p&lt;0.0001), cerebral vascular disease (CVD) (p=0.004), cancer (p=0.04), chronic obstructive pulmonary disease (COPD) (p=0.01), and renal disease (p=0.01) than survivors. In the adjusted analysis, age (Hazard Ratio (HR) 1.03, p=0.036) and renal disease (HR 2.46, p=0.045) were associated with higher in-hospital mortality. Furthermore, three independent significant factors associated with one-year mortality were identified; CHF (HR 2.18 [95% confidence interval (CI) 1.30–3.63]), cancer (HR 1.95 [95% CI 1.01–3.77]), and age (HR 1.03 [95% CI 1.01–1.05]) (Figure 1). However, patients infected with species from the Bovis group, had significantly lower risk of death at one-year (HR 0.30 [95% CI 0.10–0.89]) (Figure 1). Conclusion Having a renal disease at the time of IE diagnosis was associated with a higher in-hospital mortality in patients with streptococcal infective endocarditis. Further, congestive heart failure and cancer were associated with a higher one-year mortality, while the Bovis group was associated with a lower one-year mortality. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Zealand University Hospital Roskilde and Helsefonden (20-B-0340) Figure 1. Adjusted risk of one-year mortality

Background Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB &gt;48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86–2.41]). No difference in mortality was observed with 0–40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83–1.37]), while with 41–365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53–.95]). Conclusions Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

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