Antibiotic prophylaxis for infective endocarditis: a systematic review and meta-analysis

Background: Cardiovascular and infective complications are commonly observed in patients receiving hemodialysis (HD) with cardiovascular events and infection-related complications being the first and second leading causes of death. Infective endocarditis (IE) is characterized by inflammation of the endocardium caused by infection, typically affecting the cardiac valves and can be in acute, subacute, or chronic forms. It is a serious complication within the HD population due to their predisposition for both infection and valvular damage. Considering the frailty and burden of comorbidities in those receiving HD, management of IE in the HD population is very challenging. There has been continuous discussion and debate on optimizing the diagnostic and treatment approach of IE in this patient group to improve their clinical outcomes. Currently, reported outcomes are relatively poor and there are updates from numerous guidelines relating to advances in IE management. Summary: In this review, we will evaluate the evidence in relation to the epidemiology of HD-associated IE and discuss the important risk factors of IE in patients requiring dialysis. We will also evaluate the current recommendations regarding diagnosis and treatment for suspected or confirmed IE cases amongst HD patients and present the updated data regarding clinical outcomes relating to HD-associated IE. Key Messages: The incidence of IE in HD patients is expected to increase going forward as HD becomes more easily accessible alongside an emerging uptake of home HD. A more thorough insight into this topic is required to improve clinical practice relating to IE prevention and management in the HD population, given relatively poor clinical outcomes.

Background/Introduction Despite improvements in diagnostic and therapeutic strategies, the mortality and morbidity of infective endocarditis (IE) remain high. The incidence, outcomes, and surgical intervention of IE, particularly in an Asian population, are poorly understood and characterised, and the effect of antibiotic prophylaxis guidelines revision on the incidence of IE remains unexplored. Purpose We aim to describe temporal changes in the epidemiology and surgical intervention for IE in Hong Kong in the past 2 decades. Methods From a well-validated territory-wide database in Hong Kong, all patients aged 20 or above diagnosed with incident IE from 2000–2019 were included. The temporal trends in the incidence of IE, rate of surgical intervention, and mean Charlson Comorbidity Index (CCI) were characterised using Poisson regression analysis and expressed in annual percentage change (APC [95% CI]). Interrupted time series analysis was used to evaluate the change in incidence after the revision of antibiotic prophylaxis guidelines. The association between surgical intervention and mortality was evaluated using propensity score analytics. Temporal trends in 1-year all-cause mortality were evaluated using multivariable Cox regression. Results A total of 5,657 patients (59.9±18.3 years, 37.2% females) were included. The crude incidence remained was stable from 2000 to 2019 (APC 0.1% [−0.5 to 0.7], P=0.675), and remained unchanged following the revision of antibiotic prophylaxis guidelines in 2008 (relative risk of change 0.90 [0.64 to 1.00], P=0.065) (Figure 1). Concordant with an increase in the mean age of IE patients (APC 0.9% [0.8 to 1.1], P<0.001), the comorbidity burden grew substantially from 2000 (CCI 0.55±1.27) to 2019 (CCI 1.09±1.66). The rate of surgical intervention significantly increased from 5.3% in 2000 to 17.8% in 2019 (APC 2.7% [1.1 to 4.3], P=0.004), and surgical intervention at 1 year was associated with a 45% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.55 [0.46 to 0.65], P<0.001). Nevertheless, the crude all-cause mortality rate at 1 year increased from 27.4% in 2000 to 31.5% in 2019, with no significant trend after adjustment for demographics and comorbidities (APC −0.7% [−1.6 to 0.1], P=0.087). Conclusions In this large cohort of Asian patients, the incidence of IE remained static and did not change following the revision of antibiotic prophylaxis guidelines. Over time, patients with IE have evolved to be older and more comorbid. Despite an increasing rate of surgical intervention that conferred improved survival, the mortality of IE remained irresistibly high. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical DisciplineThe Sanming Project of HKU-SZH Cardiology

For over a half century, guidelines for the prevention of infective endocarditis (IE) have recommended antibiotic prophylaxis for certain patients receiving dental care. Much emphasis has been attributed historically on the baseless concept that dental procedures are main cause of cases of IE and dentistry carried the blame for induce endocarditis without much supporting evidence. In 2007, the American Heart Association (AHA) and British Society for Antimicrobial Chemotherapy (BSAC) updated the recommendations for IE prophylaxis before dental procedures and those recommendations are clearly evidencebased 9 . The dental treatment is a very rarely cause of IE and antibiotic prophylaxis do not give assurances as preventive. So, the value of antibiotic prophylaxis in prevention of IE has been questioned for over 20 years 3 . In reviewing the literature 2 , we did not find support that antibiotic prophylaxis actually prevents endocarditis from dental procedure only an extremely small number of cases of IE might be prevented by antibiotic prophylaxis for dental procedure. There is increasing evidence that spontaneous bacteremia are more likely to cause IE in at risk patients than specific episodes of dental treatment 568 . The majority of infective endocarditis cases caused by oral bacteria result from chewing, flossing, tooth brushing and others daily activities, and the presence of dental disease may increase the risk of bacteremia associated with these daily events 8 . Anyway the role of dental procedures in the production of infective endocarditis has probably been overestimated in relation to oral health condition thus more attention should be given to the importance of good oral hygiene and control of dental biofilm in the prevention of IE. In short, the care of the oral health must be the first step in the prevention of infective endocarditis from dental origin than antibiotic prophylaxis. Almost a year after the issued of new recommendations for prevention of IE, we still seeing most patients and health care professionals resistant to adopt this new recommendations and persisting to prescribe antibiotic prophylaxis when the need no longer exists. Only a few patients will be elected to receive antibiotic prophylaxis according to the AHA and BSAC, thus only employ in the very highest risk patients 8 . (Tables 1, 2, 3) The prescription of antibiotics carries the risk for both, patient and community, through the undesirable effects and the fact of introducing microorganisms mutants or genetically transfer the microbial resistance, respectively. The scientific community has focused the link between the overuse of antibiotics and the increasing prevalence of the drug resistant organisms 14710 . This concern is overt when evaluating ambulatory patients wich receiving short courses of antibiotics and they became an important reservoir of resistant microorganisms 7 . Antibiotic resistance is a serious incident and capable to be prevented through common sense and clinical judgment. Health care professionals have misused antibiotics for too long and carry the blame of antibiotic resistance. The risks associated with widespread antibiotic use and lack of efficacy data take us back to rethink our practice The new guidelines should be seen as great progress based on evidence that currently exists and must be followed until more evidence arise. We need further debate, especially as there are increasing environmental concerns over the misuse of antibiotics. We are now experiencing a shift thus we need time to change this scenario. Antimicrobial prophylaxis against infective endocarditis for dental procedure. A brief commentary

Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures

Spontaneous pyogenic vertebral osteomyelitis and endocarditis: Incidence, risk factors, and outcome

BackgroundWe noted an increase in infective endocarditis (IE) cases in recent years. The purpose of the study was to examine the changes in incidence, risk factors, microbiology, complications and outcome of IE in our patient population.MethodsRecords of children < 18 yrs with discharge diagnosis of IE during 2002-2020 at Children’s Hospital of Michigan, Detroit were reviewed. Modified Duke criteria were used to determine “definite” and “possible” IE cases.Results101 patients with IE were identified, representing annual incidence of 4.9/10,000 admissions. During 2002-2011 (early period), the incidence was 2.8/10,000 (33 cases). However, during 2012-2020 (late period), the incidence was 7.0/10,000 (68 cases): a 2.5-fold increase. Males were 53.4%. The age range was 1 mo – 17 yrs (median 6 yrs). Of 101 patients, 37 (36.6%) met criteria for definitive and 64 (63.4%) for possible IE. The most common predisposing conditions included congenital heart disease (CHD) (50.5%), central venous catheter (CVC) (25.7%), and immunosuppression (13.9%). CHD was more frequent in the late period (41/68, 60.3%) compared to early period (10/33, 30.3%) (p = 0.0059). Cardiac surgery had been performed in 28/51 (55%) prior to IE diagnosis. CVC related infections were more frequent in the early period (16/33, 48.5%) than the late period (10/68, 14.7%), (p = 0.0005). Overall, 16 (15.8) cases were culture negative. In culture-positive IE, S. aureus was most common (33/101, 32.7%) followed by streptococci (17), S. epidermidis (10), Gram negative bacilli (8), Enterococci (7), fungi (5) and HACEK group (4). Causative organisms were similar in both periods except for fungal organisms (5) and B. henselae (1) in the late period only. Valve replacement or valvuloplasty were performed in 19 (18.8%) patients. Complications included acute kidney injury (9) and emboli to brain (10) and to lungs (7). Mortality occurred in 15 (14.8%): 8 had CHD, 5 had CVC and 1 had fulminant MRSA infection.ConclusionMost of our IE patients had underlying medical conditions. The higher incidence of IE during the late period is likely due to an increase in the number of patients with complex cardiac conditions who underwent surgery at our institution. S. aureus was the predominant pathogen followed by streptococci. Mortality rate in our patients was 14.8%.DisclosuresAll Authors: No reported disclosures.

<i>Circulation</i> : Clinical Summaries

Statins exhibit pleiotropic effects with potential benefits in several infectious diseases, but their role in infective endocarditis (IE) remains unclear. We evaluated the impact of statin use on the frequency of IE and on key clinical outcomes in patients with IE, specifically embolic events (EE) and mortality. We conducted a meta-analysis in which the primary outcome was the frequency of IE among statin users compared with non-users. Secondary outcomes included EE and follow-up mortality (6 months to 1 year). Eleven observational studies, eight retrospective and three prospective, were included, comprising a total of 35,844 patients. The frequency of IE was significantly lower in patients receiving statins compared with non-users (odds ratio (OR): 0.52; 95% confidence interval (CI): 0.34-0.80; P=0.003). Statin-treated IE patients also had fewer EE than non-users (OR: 0.50; 95% CI: 0.26-0.96; P=0.04). Follow-up mortality was significantly reduced in IE patients using statins compared with non-users (hazard ratio (HR): 0.70; 95% CI: 0.61-0.80; P<0.00001). Statins exert anti-inflammatory, endothelial-stabilizing, and antithrombotic effects that counteract key pathological mechanisms underlying IE. In this meta-analysis, statin use was associated with a lower frequency of IE, fewer EE, and reduced follow-up mortality. This meta-analysis suggests that statins may offer protective benefits against the incidence of IE and its complications. However, these findings should be interpreted with caution and highlight the need for further research.

Infective endocarditis (IE) is a rare disease with high mortality and morbidity. In recent years, an increase in the frequency of infective endocarditis has been observed due to the increase in the survival of cases with congenital heart diseases (CHDs) and the use of central catheters. In addition to revealing the incidence of IE in our clinic, this study aimed to evaluate the demographic characteristics, predisposing factors, clinical, laboratory, microbiological, and echocardiographic findings, and the complications of follow-up of our patients diagnosed with IE in light of the literature. Thirteen patients with IE who were hospitalized in Pediatric Cardiology Clinic, Pamukkale UniversityMedical Faculty Hospital between January 2016 and August 2021 were retrospectively reviewed. The patients included in the study were evaluated in terms of demographic characteristics, predisposing factors, clinical, laboratoryand microbiological findings, echocardiography data, surgical intervention needs, and complications. The incidence of IE in our clinic was defined as the rate of IE among patients admitted to the hospital and reported as the number of patients with IE per 100,000 hospital admissions. The median age of these 13 patients was 11 (7-14) years, and the male/female ratio was 6/7. The five-year IE incidence in Pediatric Cardiology Clinic, Pamukkale UniversityMedical Faculty Hospital, was found to be 2.5 in approximately 100,000 hospital admissions. A predisposing factor was detected in all patients. Six patients (46%) had CHDs, and four patients (31%) had acquired heart disease. The other three (23%) patients were receiving immunosuppressive therapy, and these patients had long-term port catheters.Eight (62%) patients had positive blood cultures.Streptococcusviridans, Streptococcus gordonii, Staphylococcus aureus, coagulase-negativeStaphylococcus, Brucella spp, and Candida albicans were isolated in the blood cultures of these patients. IE-related complications developed in seven (54%) patients. Five (38%) had heart failure, three patients (23%) had thromboembolic events, two (15%) had glomerulonephritis, and one (8%) had thrombophlebitis. Four patients were referred to early surgery. Two patients with recurrent IE attacks were referred to surgery after their treatment was completed. The incidence of IE has shown an increase recently with increased rates of survival attributable to corrective surgeries performed for congenital heart diseases, increased prosthetic materials used in cardiac surgeries, and increased use of permanent catheters. In our study, theincidence of IE was found to be 2.5 in 100,000 hospital admissions. Our results have shown that rheumatic heart diseases, besides CHDs, are still an important risk factor for Turkey. Due to the low number of cases in IE studies in the pediatric population, there is a need for further studies to be conducted in large series in this field.

When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. We aimed to identify independent risk factors for IE in patients with VGS BSI. This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. By crosslinking nationwide registries from 2010 to 2017, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. In total 69021, distributed with 15350, 16726, 19251, and 17694 BSIs were identified in the periods of 2010-2011, 2012-2013, 2014-2015, and 2016-2017, respectively. Patients with E. faecalis had the highest prevalence of IE (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis and Streptococcus spp. increased significantly (P = 0.0005 and P = 0.03, respectively). Male patients had a higher prevalence of IE for E. faecalis, Streptococcus spp., and CoNS compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI.

Prevalence of Infective Endocarditis in Patients with Positive Blood Cultures: A Danish Nationwide Study

Background Infective endocarditis (IE) is a complex infectious disease with high morbidity and mortality. The inflammation mechanism of IE is a complex network including interactions of inflammatory cytokines and other components of host response. As an important inflammation marker, the prediction ability of neutrophil-to-lymphocyte ratio (NLR) in IE deserves further investigation. Methods NLR values were measured and compared between IE patients and healthy controls, good and bad clinical outcome groups. The receiver operating characteristic curves (ROCs) of NLR and cut-off values were measured in IE patients, pathogen-subgroups, and different clinical outcome groups. Results There were 678 IE patients and 2520 healthy controls enrolled in our study. The number of good and bad clinical outcome patients was 537 and 141, respectively. The value of NLR was significantly higher in IE patients than healthy controls (6.29 ± 9.36 vs. 1.87 ± 0.34, p < 0.001), and the area under the ROC (AUC) was 0.817 (95% CI (0.794, 0.839), p < 0.001). The critical value of NLR for diagnosis of IE was 2.68, with a sensitivity of 69%, and a specificity of 88%. The value of NLR was significantly higher in bad clinical outcome patients than in good clinical outcome patients (5.8 ± 6.02 vs. 3.62 ± 2.61, p < 0.001). The critical value of NLR to predict the outcome of IE was 5.557, with a sensitivity of 39.0% and a specificity of 85.3%. Conclusions NLR is a predictive marker for IE patients, especially in Gram-negative bacteria and Gram-positive bacteria-infected IE patients. NLR also can predict the outcome of IE. Early detecting NLR upon admission may assist in early diagnosis and risk stratification of patients with IE.

Context: Surgical site infection (SSI) is responsible for significant morbidity, prolonged hospital stays, and increased costs. Infectious endocarditis (IE) is a rare but serious complication of bacteremia, particularly that resulting from Staphylococcus aureus SSI. The VIRSTA score predicts the risk of IE and determines the priority of transthoracic echocardiography (TTE) in patients with S. aureus bacteremia. The aim of the study was to (1) assess the performance of the VIRSTA score and (2) determine the usefulness of TTE in S. aureus bacteremia related to spinal SSI. Materials and Methods: We carried out a retrospective study of consecutive patients with spinal SSI and S. aureus bacteremia at two university hospitals in France (Bordeaux and Tours) from January 2009 to January 2023. We collected the patients' clinical and surgical characteristics at baseline, VIRSTA score items, TTE results, and medicosurgical management. The associations of these parameters with IE were assessed using the chi-square test and logistic regression models. Results: Of 82 patients with spinal SSI and S. aureus bacteremia, only 1 (1.21%) developed IE. Thirteen patients did not benefit from TTE during hospitalization and were considered free of IE after clinical follow-up. Diabetes mellitus (p < 0.04) and the presence of severe sepsis or septic shock (p < 0.03) were significantly associated with the presence of IE in this population. Conclusions: Incidence of IE in patients with spinal SSI and S. aureus bacteremia is low. The VIRSTA score has high sensitivity but is not accurate for identifying patients at high risk for IE and systematic performance of TTE is complex and not useful in this setting. Level of Evidence: IV.

Background: Infective endocarditis (IE) is a severe disease with high morbidity and mortality rate. Poor immune response and autoimmunity have been reported in patients with IE and result in different complications such as severe sepsis, glomerulonephritis, arthritis, coagulopathy and embolization. This study aims to investigate the role of immune system in the pathogenesis of IE through assessment of memory and naïve T and B lymphocytes and T regulatory cells (T regs). Methods: Twenty IE patients and twenty healthy age and sex matched donors were included in the study. Flow cytometry was used to asses the naïve and memory subsets of peripheral blood lymphocytes using cell surface markers CD4, CD19, CD45RO, CD45RA, CD27 and IgD. T regs were characterized by co-expression of CD25/FoxP3 among the CD4+ T cells. Results: IE patients had significant lower number of CD45RO+CD4+ memory T cells when compared to healthy control (p=0.03). No differences were observed regarding CD45RA+CD4+ naïve T cells, CD19+CD27+ memory B cells and CD19+IgD+ naïve B cells between the IE patients and healthy control. However, IE patients had significantly lower percentage and number of T regs (p=0.039, p=0.009 respectively). Conclusion: IE patients suffer from immune system dysfunction which contribute to the disease course and complications. The decrease in the CD45RO+CD4+ memory T cells can partly explain why IE patients cannot effectively clear the infection before the invading pathogen replicate and cause tissue damage. The defect in T regs may underlie the autoimmunity and occurrence of autoantibodies reported in IE patients