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In this randomized, controlled trial conducted at Danish cardiac centers, intravenous antibiotic therapy was compared with partial oral antibiotic therapy for the treatment of bacterial endocarditis. The outcomes were similar in the two groups.

BACKGROUNDNovel therapeutic approaches are critically needed for Staphylococcus aureus bloodstream infections (BSIs), particularly for methicillin-resistant S. aureus (MRSA). Exebacase, a first-in-class antistaphylococcal lysin, is a direct lytic agent that is rapidly bacteriolytic, eradicates biofilms, and synergizes with antibiotics.METHODSIn this superiority-design study, we randomly assigned 121 patients with S. aureus BSI/endocarditis to receive a single dose of exebacase or placebo. All patients received standard-of-care antibiotics. The primary efficacy endpoint was clinical outcome (responder rate) on day 14.RESULTSClinical responder rates on day 14 were 70.4% and 60.0% in the exebacase + antibiotics and antibiotics-alone groups, respectively (difference = 10.4, 90% CI [-6.3, 27.2], P = 0.31), and were 42.8 percentage points higher in the prespecified exploratory MRSA subgroup (74.1% vs. 31.3%, difference = 42.8, 90% CI [14.3, 71.4], ad hoc P = 0.01). Rates of adverse events (AEs) were similar in both groups. No AEs of hypersensitivity to exebacase were reported. Thirty-day all-cause mortality rates were 9.7% and 12.8% in the exebacase + antibiotics and antibiotics-alone groups, respectively, with a notable difference in MRSA patients (3.7% vs. 25.0%, difference = -21.3, 90% CI [-45.1, 2.5], ad hoc P = 0.06). Among MRSA patients in the United States, median length of stay was 4 days shorter and 30-day hospital readmission rates were 48% lower in the exebacase-treated group compared with antibiotics alone.CONCLUSIONThis study establishes proof of concept for exebacase and direct lytic agents as potential therapeutics and supports conduct of a confirmatory study focused on exebacase to treat MRSA BSIs.TRIAL REGISTRATIONClinicaltrials.gov NCT03163446.FUNDINGContraFect Corporation.

The 5-year outcomes from the Partial Oral Treatment of Endocarditis (POET) trial show continued effectiveness of oral antibiotic therapy as compared with intravenous antibiotic therapy for endocarditis.

The timing of surgery in the context of acute endocarditis associated with valvular failure and large vegetations is controversial. In this randomized trial in South Korea, early surgery was associated with fewer clinically significant embolic events than conventional treatment. Despite advances in medical and surgical treatment, infective endocarditis remains a serious disease that carries a considerable risk of death and morbidity. 1 , 2 The role of surgery in the treatment of infective endocarditis has been expanding, and current guidelines advocate surgical management for complicated left-sided infective endocarditis. 2 , 3 Early surgery is strongly indicated for patients with infective endocarditis and congestive heart failure, 1 , 4 but the indications for surgical intervention to prevent systemic embolism remain to be defined. 5 Early identification of patients with large vegetations and a high risk of embolism, 6 increased experience with complete excision of infected tissue and valve . . .

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p  = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

•What is already known:•Much of the previous studies on infective endocarditis(IE) is often based on cohorts from tertiary hospitals or retrospective registry studies, which may not represent the whole IE population, creating a need for nationwide characterization.•What this study adds:•The NIDUS registry is a validated national cohort encompassing all IE cases in Denmark from 2016 to 2021, including 3,557 patients (79.6% classified as definite IE and 20.4% as possible IE).•It provides comprehensive insights into IE demographics, clinical features, comorbidities, and outcomes from a contemporary nationwide cohort: most patients presented with fever (61.1%), followed by dyspnea (33.0%) and myalgias (27.0%). Sepsis was identified in 828 (23.3%) patients, and 378 (10.6%) exhibited signs of embolization at admission.•In the NIDUS registry, in-hospital mortality was 17.3%, 1-year mortality reached 31.3%, 19.4% of the patients underwent surgical treatment during hospitalization, and Staphylococcus aureus was the most common pathogen. Most knowledge on infective endocarditis (IE) comes from large IE cohorts that include patients from tertiary hospitals, leading to referral bias and retrospective population-based studies. This highlights the need for a more detailed characterization of IE in unselected patient cohorts. In the National Danish Endocarditis Studies (NIDUS) registry, all hospitalizations in Denmark from 2016 to 2021 with an IE diagnosis were reviewed and validated using electronic medical records (EMR) by healthcare professionals under the supervision of IE experts. Episodes meeting the European Society of Cardiology 2015 modified diagnostic criteria for possible or definite IE were included. We screened 4390 unique patients, of whom 3557 (81%) were included in the NIDUS registry. Of the 3557 unique patients, 2832 (79.6%) were classified as definite IE and 725 (20.4%) as possible IE. The age was 73.7 years, and most patients were men (68.3%). In total, 689 (19.4%) underwent surgery during hospitalization. The most frequent comorbidities were diabetes (23.7%), heart failure (18.7%), and chronic kidney disease (17.4%). Most patients presented with fever (61.1%), followed by dyspnea (33.0%) and myalgias (27.0%). Sepsis was found in 828 (23.3%) patients, while 378 (10.6%) had signs of embolization at admission. Positive blood cultures were identified in 3191 (89.7%) patients, and the most frequent microbiological etiology was Staphylococcus aureus (31.9%). The in-hospital mortality was 17.3%, and the 1-year mortality rate was 31.3%. The NatIonal Danish endocarditis studies (NIDUS) registry provides comprehensive, granular, and nationwide data on a cohort of patients with infective endocarditis, revealing that when selection is not restricted to tertiary hospitals or voluntary registries, some important differences emerge. Patients with IE are on average older, have a similar burden of comorbidities, and less often undergo surgery. Minimizing selection bias with the use of a national registry provides a clearer picture of IE as it occurs in real-world clinical settings. [Display omitted]

Infective endocarditis (IE) is an increasingly prevalent condition with relatively high mortality, whose epidemiology has become more complex with an aging population, an increased number of comorbidities, and an increasing incidence of health-care associated IE. Epidemiological data on the causative microorganisms of IE, prevalence of involvement of the different cardiac valves, and IE-associated mortality are clinically relevant. Eligible studies were identified through a systematic search of PubMed/MEDLINE database from 2010 to 2020, and a random effects model meta-analysis was conducted. 133 studies comprising 132,584 patients from six continents were included in this systematic review. The most common causative agents were Staphylococci species in 36% of cases, followed by Streptococci species (26%) and Enterococci species (10%). Out of studies that provided further speciation, the predominant species was Staphylococcus aureus with an incidence of 29%, followed by Viridans group Streptococcus (12%). The short-term mortality rate (defined as in-hospital or 30-day mortality) was 17%. The highest mortality was reported in studies from Latin America with a mean mortality rate of 33% and the lowest mortality was reported in studies from Oceania at 13%. The aortic valve was the most commonly affected valve (46%), followed closely by the mitral valve (43%). The prevalence of tricuspid valve IE was 7% and multivalvular IE occurred in 14% of cases. Our study highlights a shift in epidemiological profile of IE over the last decade with S. aureus identified as the most common causative microorganism of IE. PROSPERO CRD42024602342.

Despite improvements in medical and surgical therapies, infective endocarditis is associated with poor prognosis and remains a therapeutic challenge. Many factors affect the outcome of this serious disease, including virulence of the microorganism, characteristics of the patients, presence of underlying disease, delays in diagnosis and treatment, surgical indications, and timing of surgery. We review the strengths and limitations of present therapeutic strategies and propose future directions for better management of endocarditis according to the most recent research. Novel perspectives on the management of endocarditis are emerging and offer hope for decreasing the rate of residual deaths by accelerating the process of diagnosis and risk stratification, reducing delays in starting antimicrobial therapy, rapid transfer of high-risk patients to specialised medico-surgical centres, development of new surgical methods, and close long-term follow-up.

BackgroundStaphylococcus aureus infective endocarditis (SA-IE) remains a serious condition, with in-hospital mortality rates ranging between 30% and 40%. While current guidelines suggest surgery may be considered in all SA-IE cases, robust data comparing outcomes between patients undergoing surgery and those receiving medical therapy alone are scarce.MethodsUsing the NatIonal Danish endocarditis stUdieS registry, we identified all patients with left-sided SA-IE between 2016 and 2021. Patients were categorised into two groups: surgical and non-surgical. Baseline characteristics were assessed, and in-hospital mortality was analysed using crude estimates and multivariable Cox regression.ResultsOf 918 patients identified, 160 (17%) patients underwent surgery (median age 63.7 years; 73% male), and 758 (83%) were treated non-surgically (median age 75.0 years; 58% male). Surgical patients had fewer comorbidities, including diabetes (18% vs 27%) and congestive heart failure (6% vs 19%). Surgical patients presented at admission with more severe conditions, including larger vegetations (56% vs 21%), sepsis (53% vs 33%) and emboli (24% vs 10%). Crude in-hospital mortality was lower in the surgical group (17% vs 28%), as was 1 year mortality (21% vs 45%). After adjusting for confounders, there was no significant difference in adjusted in-hospital mortality between the groups (HR 0.75 (95% CI 0.47 to 1.19)); however, 1-year mortality was statistically significantly lower in surgical patients (HR 0.61 (95% CI 0.41 to 0.91)).ConclusionIn patients with SA-IE, surgical patients were younger and had fewer comorbidities, but had more severe disease status at admission, compared with non-surgical patients. Surgery was associated with lower 1-year mortality, but the heterogeneity of this patient population limits firm conclusions about the superiority of either treatment strategy.

ObjectiveTo develop and validate a calculator to predict the risk of in-hospital mortality in patients with active infective endocarditis (IE) undergoing cardiac surgery.MethodsThousand two hundred and ninety-nine consecutive patients with IE were prospectively recruited (1996–2014) and retrospectively analysed. Left-sided patients who underwent cardiac surgery (n=671) form our study population and were randomised into development (n=424) and validation (n=247) samples. Variables statistically significant to predict in-mortality were integrated in a multivariable prediction model, the Risk-Endocarditis Score (RISK-E). The predictive performance of the score and four existing surgical scores (European System for Cardiac Operative Risk Evaluation (EuroSCORE) I and II), Prosthesis, Age ≥70, Large Intracardiac Destruction, Staphylococcus, Urgent Surgery, Sex (Female) (PALSUSE), EuroSCORE ≥10) and Society of Thoracic Surgeons’s Infective endocarditis score (STS-IE)) were assessed and compared in our cohort. Finally, an external validation of the RISK-E in a separate population was done.ResultsVariables included in the final model were age, prosthetic infection, periannular complications, Staphylococcus aureus or fungi infection, acute renal failure, septic shock, cardiogenic shock and thrombocytopaenia. Area under the receiver operating characteristic curve in the validation sample was 0.82 (95% CI 0.75 to 0.88). The accuracy of the other surgical scores when compared with the RISK-E was inferior (p=0.010). Our score also obtained a good predictive performance, area under the curve 0.76 (95% CI 0.64 to 0.88), in the external validation.ConclusionsIE-specific factors (microorganisms, periannular complications and sepsis) beside classical variables in heart surgery (age, haemodynamic condition and renal failure) independently predicted perioperative mortality in IE. The RISK-E had better ability to predict surgical mortality in patients with IE when compared with other surgical scores.