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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 . . .

To evaluate trends in bacterial causes of valvular endocarditis in swine, we retrospectively analyzed 321 cases diagnosed at Iowa State University Veterinary Diagnostic Laboratory (Ames, IA, USA) during May 2015--April 2020. Streptococcus gallolyticus was the causative agent for 7.59% of cases. This emerging infection in swine could aid study of endocarditis in humans.

The data on infective endocarditis after transcatheter aortic valve implantation (TAVI) is scarce and limited to case reports and case series in the literature. It is the need of the hour to analyze the available data on post-TAVI infective endocarditis from the available literature. The objectives of this systematic review were to evaluate the incidence of infective endocarditis after transcatheter aortic valve implantation, its microbiological profile and clinical outcomes. It will help us to improve the antibiotic prophylaxis strategies and treatment options for infective endocarditis in the context of TAVI. EMBASE, Medline and the CENTRAL trials registry of the Cochrane Collaboration were searched for articles on infective endocarditis in post-TAVI patients till October 2018. Eleven articles were included in the systematic review. The outcomes assessed werethe incidence of infective endocarditis, its microbiological profile andclinical outcomes including major adverse cardiac event (MACE), net adverse clinical event (NACE), surgical intervention and valve-in-valve procedure. The incidence of infective endocarditis varied from 0%-14.3% in the included studies, the mean was3.25%. The average duration of follow-up was 474 days (1.3 years). Enterococci were the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus (16.1%) and coagulase-negative Staphylococcus species (14.7%). The mean in-hospital mortality and mortality at follow-up was 29.5% and 29.9%, respectively. The cumulative incidence of heart failure, stroke and major bleeding were 37.1%, 5.3% and 11.3%,respectively. Only a single study by Martinez-Selles et al. reported arrhythmias in 20% cases. The septic shock occurred in 10% and 27.7% post-TAVI infective endocarditis patients according to 2 studies. The surgical intervention and valve-in-valve procedure were reported in 11.4% and 6.4% cases, respectively. The incidence of post-TAVI infective endocarditis is low being 3.25% but it is associated with high mortality and complications. The most common complication is heart failure with a cumulative incidence of 37.1%. Enterococciare the most common causative organism isolated from 25.9% of cases followed by Staphylococcus aureus in 16.1% of cases. Appropriate measures should be taken to prevent infective endocarditis in post-TAVI patients including adequate antibiotics prophylaxis directed specifically against these organisms. PROSPERO registration number CRD42018115943.

•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]

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.

In patients with Staphylococcus aureus bacteremia or right-sided endocarditis, daptomycin was shown to be noninferior to standard antimicrobial therapy (vancomycin or an antistaphylococcal penicillin with low-dose gentamicin). Microbiologic evidence of treatment failure was more common in the daptomycin group, whereas treatment failure caused by an adverse event occurred more often in the standard-therapy group. In patients with Staphylococcus aureus bacteremia or right-sided endocarditis, daptomycin was shown to be noninferior to standard antimicrobial therapy. Staphylococcus aureus is a leading cause of bacteremia 1 , 2 and endocarditis. 3 , 4 S. aureus bacteremia is associated with serious complications, including endocarditis, in 30 to 40 percent of cases. 5 , 6 Treatment options for bacteremia and endocarditis caused by S. aureus, particularly methicillin-resistant S. aureus (MRSA), are limited. Vancomycin, the standard therapy for bloodstream infections attributable to MRSA, has been associated with suboptimal outcomes. 7 – 10 New agents for the treatment of S. aureus bacteremia and endocarditis are needed. Daptomycin is a cyclic lipopeptide antibiotic that is rapidly bactericidal in vitro against most clinically relevant gram-positive bacteria, including S. aureus . 11 – . . .

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.