Lars Olaison

Clinical Presentation, Etiology, and Outcome of Infective Endocarditis in the 21st Century: The International Collaboration on Endocarditis–Prospective Cohort Study

BACKGROUND We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. METHODS Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. RESULTS The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. CONCLUSIONS In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

EPIDEMIOLOGIC ASPECTS OF INFECTIVE ENDOCARDITIS IN AN URBAN POPULATION. A 5-YEAR PROSPECTIVE STUDY

A prospective study of the epidemiology of infective endocarditis (IE) in a well-defined urban population of 428,000 inhabitants during a 5-year period was carried out. All patients were treated in the same institution, and history, diagnostic procedures, and treatment were standardized. Of 233 consecutive suspected episodes of IE, 127 fulfilled the modified von Reyn criteria. After patients not living in the defined area were excluded, 99 episodes in 90 patients were analyzed in the epidemiologic part of the study. Of these, 33 episodes were definite endocarditis, verified by surgery or autopsy; 35 probable; and 31 possible endocarditis episodes. Another 34 episodes were found retrospectively and are included in the incidence calculation. The crude incidence was calculated to be 6.2/100,000 inhabitants per year, which is high compared to earlier studies. Adjusted to the population of Sweden, the incidence was 5.9/100,000 inhabitants per year. The annual incidence was higher for women, 6.6/100,000, than for men, 5.8/100,000. In the oldest age-group (80-89 years) the annual incidence was 22/100,000 in the prospective study and 30/100,000 if retrospective cases were included. Contrary to almost all other studies, we did not find a male predominance among our cases. Only 7% of patients were intravenous drug abusers, and 15% had a prosthetic valve. The most common bacteria were methicillin-susceptible Staphylococcus aureus (31%) and alpha-streptococci (28%); 12% of episodes were culture negative. The mortality from IE in the population was 1.4/100,000 inhabitants per year. A higher-than-expected incidence of IE was found, especially among older patients and women.

Staphylococcus aureus Native Valve Infective Endocarditis: Report of 566 Episodes from the International Collaboration on Endocarditis Merged Database

BACKGROUND Staphylococcus aureus native valve infective endocarditis (SA-NVIE) is not completely understood. The objective of this investigation was to describe the characteristics of a large, international cohort of patients with SA-NVIE. METHODS The International Collaboration on Endocarditis Merged Database (ICE-MD) is a combination of 7 existing electronic databases from 5 countries that contains data on 2212 cases of definite infective endocarditis (IE). RESULTS Of patients with native valve IE, 566 patients [corrected] had IE due to S. aureus, and 1074 patients had IE due to pathogens other than S. aureus (non-SA-NVIE). Patients with S. aureus IE were more likely to die (20% vs. 12%; P < .001), to experience an embolic event (61% [corrected] vs. 31%; P < .001), or to have a central nervous system event (21% [corrected] vs. 13%; P < .001) and were less likely to undergo surgery (26% vs. 39%; P < .001) than were patients with non-SA-NVIE. Multivariate analysis of prognostic factors of mortality identified age (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7), periannular abscess (OR, 2.4; 95% CI, 1.0 [corrected] -5.6), heart failure (OR, 3.9; 95% CI, 2.3-6.7), and absence of surgical therapy (OR, 2.3; 95% CI, 1.3-4.2) as variables that were independently associated with mortality in patients with SA-NVIE. After adjusting for patient-, pathogen-, and treatment-specific characteristics by multivariate analysis, geographical region was also found to be associated with mortality in patients with SA-NVIE (P < .001). CONCLUSIONS S. aureus is an important and common cause of IE. The outcome of SA-NVIE is worse than that of non-SA-NVIE. Several clinical parameters are independently associated with mortality for patients with SA-NVIE. The clinical characteristics and outcome of SA-NVIE vary significantly by geographic region, although the reasons for such regional variations in outcomes of SA-NVIE are unknown and are probably multifactorial. A large, prospective, multinational cohort study of patients with IE is now under way to further investigate these observations.

Analysis of the Impact of Early Surgery on In-Hospital Mortality of Native Valve Endocarditis Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment-Selection Bias

Background— The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. Methods and Results— Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] −5.9%, P<0.001). With a combined instrument, the instrumental-variable–adjusted ARR in mortality associated with early surgery was −11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR −10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR −17.3%, P<0.001), systemic embolization (ARR −12.9%, P=0.002), S aureus NVE (ARR −20.1%, P<0.001), and stroke (ARR −13%, P=0.02) but not those with valve perforation or congestive heart failure. Conclusions— Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.

Cerebrovascular Complications in Patients with Left-Sided Infective Endocarditis Are Common: A Prospective Study Using Magnetic Resonance Imaging and Neurochemical Brain Damage Markers

Background. @nbsp; Cerebrovascular complications (CVCs) have remained a major therapeutic and prognostic challenge associated with infective endocarditis, and definite risk factors have not been fully elucidated. This prospective study was designed to the evaluate the total incidence of CVC associated with infective endocarditis and major risk factors. Methods. @nbsp; During 2 study periods, from June 1998 through April 2001 and from September 2002 through January 2005, patients were prospectively enrolled in the study regardless of neurological symptoms. Study patients underwent neurological examinations and magnetic resonance imaging of the brain, and cerebrospinal fluid analyses of inflammatory and neurochemical markers of brain damage (neurofilament protein and glial fibrillary acidic protein) were performed. Results. @nbsp; Sixty patients who experienced episodes of left-sided infective endocarditis were evaluated; 35% of these patients experienced a symptomatic CVC. Silent cerebral complications were detected in another 30% of the patients, and the total CVC rate was 65% (95% confidence interval, 58%-72%). Five percent of patients experienced their first neurological symptom after the initiation of antibiotic treatment without prior surgery. No new symptomatic CVCs were detected after 10 days of antibiotic treatment. No neurological deterioration was observed after surgery in patients who were established to have a symptomatic CVC preoperatively. A larger heart valvular vegetation size was a risk factor for both symptomatic and silent CVCs; Staphylococcus aureus etiology conferred a higher risk for symptomatic cerebral complication only. Conclusions. @nbsp; The use of sensitive methods of detection indicates that the incidence of CVC associated with infective endocarditis is high, but the risk for neurological deterioration during cardiac surgery after a CVC is lower than previously assumed. The major mechanism behind cerebral complications associated with infective endocarditis is cerebral embolization, although the dominant neurological symptoms vary considerably.

Current best practices and guidelines: Indications for surgical intervention in infective endocarditis

Optimal diagnosis and management of patients with infective endocarditis requires sound clinical judgment based on extensive experience. This is especially important in regard to the indications and timing for surgery. To achieve the best possible outcomes, surgical intervention during treatment is required in 25% to 30% of patients with infective endocarditis. Heart failure and progressive left-sided valvular dysfunction are the most common indications for operation. Valve repair should be considered as an alternative to valve replacement whenever feasible, especially in younger patients. Successful management of perivalvular abscesses and prosthetic valve infections requires radical removal of infected tissue followed by reconstructive procedures performed by experienced surgeons. Emergency or urgent surgery should seldom be delayed.

Enterococcal Endocarditis in Sweden, 1995-1999: Can Shorter Therapy with Aminoglycosides Be Used?

A 5-year nationwide prospective study in Sweden during 1995-1999 identified 881 definite episodes of infective endocarditis. Definite enterococcal endocarditis was diagnosed in 93 episodes (11%), the largest series of enterococcal endocarditis so far presented. Mortality during treatment was 16%, the relapse rate was 3%, and clinical cure was achieved in the remaining 81% of the episodes. Clinical cure was achieved with a median duration of cell wall-active antimicrobial therapy of 42 days combined with an aminoglycoside (median treatment time, 15 days). International guidelines generally recommend a 4-6-week combined synergistic treatment course with a cell wall-active antibiotic and an aminoglycoside. Treatment regimens in Sweden often include a shortened aminoglycoside treatment course in order to minimize adverse effects in older patients. Fatal outcome seemed not to be due to the shortened aminoglycoside therapy course. In many enterococcal endocarditis episodes, duration of aminoglycoside therapy could probably be shortened to 2-3 weeks.

Native Valve Endocarditis Due to Coagulase-Negative Staphylococci: Report of 99 Episodes from the International Collaboration on Endocarditis Merged Database

Using a large cohort of patients from the International Collaboration on Endocarditis Merged Database, we compared coagulase-negative staphylococcal (CoNS) native-valve endocarditis (NVE) to NVE caused by more common pathogens. Rates of heart failure and mortality were similar between patients with CoNS NVE and patients with Staphylococcus aureus NVE, but rates for both groups were significantly higher than rates for patients with NVE due to viridans streptococci. These results emphasize the importance of CoNS as a cause of NVE and the potential for serious complications with this infection.

Prognostic Factors in 61 Cases of Staphylococcus aureus Prosthetic Valve Infective Endocarditis from the International Collaboration on Endocarditis Merged Database

Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with a high mortality rate, but prognostic factors have not been clearly elucidated. The International Collaboration on Endocarditis merged database (ICE-MD) contained 2212 cases of definite infective endocarditis (as defined using the Duke criteria), 61 of which were SA-PVIE. Overall mortality rate was 47.5%, stroke was associated with an increased risk of death, and early valve replacement was not associated with a significant survival benefit in the whole population; however, patients who developed cardiac complications and underwent early valve replacement had the lowest mortality rate (28.6%).

A clinical study of culture-negative endocarditis.

Culture-negative infective endocarditis (CNE) is a diagnostic problem in spite of improved echocardiographic and blood culturing techniques. We conducted the present study to estimate the proportion of CNE in patients with infective endocarditis, to investigate data regarding risk factors, and to evaluate the Duke and the modified Beth Israel criteria in patients with CNE.We evaluated 820 consecutive suspected episodes of infective endocarditis in adults at the Departments of Infectious Diseases in Göteborg and Borås, Sweden (1984–1996). All patients were diagnosed and treated according to a protocol; 487 episodes were identified as infective endocarditis. Episodes with absence of bacterial growth at blood culture were defined as CNE and were classified with the Duke and the modified Beth Israel criteria.We identified 116 CNE episodes (median age, 67 yr). Mortality was 7%, and in 15%, cardiac surgery was performed. The Duke criteria classified 20 definite, 80 possible, and 16 reject episodes. The modified Beth Israel criteria distinguished 13 definite, 15 probable, 27 possible, and 61 reject episodes. The proportion of CNE among patients with infective endocarditis varied from 19% to 27% at the 2 departments. Antibiotic treatment preceded blood culture in 45% of the CNE episodes.About 20% in a Scandinavian population of infective endocarditis patients have CNE. Antibiotic pretreatment explains less than 50% of all CNE episodes. The Duke criteria are more sensitive but less specific than the modified Beth Israel criteria in classifying patients with CNE.