Staphylococcus aureus bacteremia (SAB) remains a significant contributor to both community-acquired and healthcare-associated bloodstream infections. SAB exhibits a high recurrence rate and mortality rate, leading to numerous clinical treatment challenges. Particularly, since the outbreak of COVID-19, there has been a gradual increase in SAB patients, with a growing proportion of (Methicillin-resistant Staphylococcus aureus) MRSA infections. Therefore, we have constructed and validated a pediction model for recurrent SAB using machine learning. This model aids physicians in promptly assessing the condition and intervening proactively.

The patients data is sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database version 2.2. The patients were divided into training and testing datasets using a 7:3 random sampling ratio. The process of feature selection employed two methods: Recursive Feature Elimination (RFE) and Least Absolute Shrinkage and Selection Operator (LASSO). Prediction models were built using Extreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), Support Vector Machine (SVM), and Artificial Neural Network (ANN). Model validation included Receiver Operating Characteristic (ROC) analysis, Decision Curve Analysis (DCA), and Precision-Recall Curve (PRC). We utilized SHAP (SHapley Additive exPlanations) values to demonstrate the significance of each feature and explain the XGBoost model.

After screening, MRSA, PTT, RBC, RDW, Neutrophils_abs, Sodium, Calcium, Vancomycin concentration, MCHC, MCV, and Prognostic Nutritional Index(PNI) were selected as features for constructing the model. Through combined evaluation using ROC、 DCA and PRC, XGBoost demonstrated the best predictive performance, achieving an AUC value of 0.76 (95% CI: 0.66-0.85) in ROC and 0.56 (95% CI: 0.37-0.75) in PRC. Building a website based on the Xgboost model. SHAP illustrated the feature importance ranking in the XGBoost model and provided examples to explain the XGBoost model.

The adoption of XGBoost for model development holds widespread acceptance in the medical domain. The prediction model for recurrent SAB, developed by our team, aids physicians in timely diagnosis and treatment of patients.

Staphylococcus aureus (S. aureus) bloodstream infection (SAB) remains a major clinical challenge despite appropriate antimicrobial therapy. Recent studies have suggested the potential benefits of P2Y12 inhibitors in SAB treatment, but controversy persists regarding their optimal use. Moreover, the effects of P2Y12 inhibitors in Japanese patients remain unclear. This study aimed to evaluate the effects of using P2Y12 inhibitors before admission on outcomes in Japanese patients with SAB.

This retrospective study involved Japanese patients aged 18 years and older with S. aureus-positive blood cultures at Aichi Medical University Hospital in Japan from March 2015 to April 2023. The primary outcome was the rate of persistent bacteremia among patients with follow-up blood cultures within seven days. The secondary outcomes were 30-day and in-hospital mortality rates and bleeding events during hospitalization.

During the study period, 238 patients with SAB (19 P2Y12 inhibitor users and 219 non-users) were enrolled. The median age was 77 years, and 38.7% of the patients were female individuals. The overall rate of methicillin-resistant S. aureus as a percentage of S. aureus was 37.9%, with no significant difference between the groups. The rate of persistent bacteremia was significantly lower in P2Y12 inhibitor users than in non-users (0% vs. 20.6%, p=0.03). The Kaplan-Meier survival curve for the 30-day and in-hospital mortality rates showed no significant difference between the groups (log-rank test, p=0.25 and p=0.20, respectively). No bleeding events occurred in either group.

This retrospective study suggests that Japanese patients with SAB using P2Y12 inhibitors prior to admission as adjunctive therapy have a higher rate of microbiological clearance than non-users. However, further prospective studies are needed to determine the benefits of adding P2Y12 inhibitors to standard antimicrobial therapy for SAB.

Numerous cellular processes are regulated in response to the metabolic state of the cell, and one such regulatory mechanism involves lysine acetylation. Lysine acetylation has been proven to play an important role in the virulence of Streptococcus mutans, a major cariogenic bacterial species. S. mutans' glucosyltransferases (Gtfs) are responsible for synthesizing extracellular polysaccharides (EPS) and contributing to biofilm formation. One of the most common nonsteroidal anti-inflammatory drugs is acetylsalicylic acid (ASA), which can acetylate proteins through a nonenzymatic transacetylation reaction. Herein, we investigated the inhibitory effects of ASA on S. mutans. ASA treatment was observed to impede the growth of S. mutans, leading to a reduction in the production of water-insoluble EPS and the formation of biofilm. Moreover, ASA decreased the enzyme activity of Gtfs while increasing the protein acetylation level. The in vivo anticaries efficacy of ASA has further been proved using the rat caries model. In conclusion, ASA as an acetylation agent attenuated the cariogenic virulence of S. mutans, suggesting the potential value of protein acetylation on antimicrobial and anti-biofilm applications to S. mutans.

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate the ability of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, such as when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis.

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo-inflammatory response. Platelet P2Y12 receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet-leucocyte aggregation and activation via platelet P-selectin. Much evidence for the role of platelet P2Y12 receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y12 receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y12 receptors are prominent mediators of inflammation and P2Y12 receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.

Staphylococci sp. are the most commonly associated pathogens in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations, and the protracted infection courses, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid's version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. Thirty-five studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored, giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. The goal of this study is to attain a better understanding on the molecular pathways involved in infective endocarditis supported by S. aureus and whether therapeutic avenues for the prevention and treatment of IE can be obtained. The use of antibiotic-treated allogeneic tissues have marked antibacterial action, thereby becoming the ideal substitute in native and prosthetic valvular infections. However, the development of effective vaccines against S. aureus still requires in-depth studies.

Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.

Objectives: This present study aimed to infer the association between aspirin exposure prior to ICU admission and the clinical outcomes of patients with Sepsis-associated acute respiratory failure (S-ARF). Methods: We obtained data from the Medical Information Mart for Intensive Care IV 2.0. Patients were divided into pre-ICU aspirin exposure group and Non-aspirin exposure group based on whether they took aspirin before ICU admission. The primary outcome is 28-day mortality. Augmented inverse propensity weighted was used to explore the average treatment effect (ATE) of the pre-ICU aspirin exposure. A generalized additive mixed model was used to analyze the longitudinal data of neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), oxygenation index (P/F), dynamic lung compliance (Cdyn), mechanical power (MP), and mechanical power normalized to predicted body weight (WMP) in the two groups. A multiple mediation model was constructed to explore the possible mediators between pre-ICU aspirin exposure and outcomes of patients with S-ARF. Results: A total of 2090 S-ARF patients were included in this study. Pre-ICU aspirin exposure decreased 28-day mortality (ATE, -0.1945, 95% confidence interval [CI], -0.2786 to -0.1103, p < 0.001), 60-day mortality (ATE, -0.1781, 95% Cl, -0.2647 to -0.0915, p < 0.001), and hospital mortality (ATE, -0.1502, 95%CI, -0.2340 to -0.0664, p < 0.001). In subgroup analysis, the ATE for 28-day mortality, 60-day mortality, and hospital mortality were not statistically significant in the coronary care unit group, high-dose group (over 100 mg/d), and no invasive mechanical ventilation (IMV) group. After excluding these non-beneficiaries, Cdyn and P/F ratio of the pre-ICU aspirin exposure group increased by 0.31mL/cmH₂O (SE, 0.21, p = 0.016), and 0.43 mmHg (SE, 0.24, p = 0.041) every hour compared to that of non-aspirin exposure group after initialing IMV. The time-weighted average of NLR, Cdyn, WMP played a mediating role of 8.6%, 24.7%, and 13% of the total effects of pre-ICU aspirin exposure and 28-day mortality, respectively. Conclusion: Pre-ICU aspirin exposure was associated with decreased 28-day mortality, 60-day mortality, and hospital mortality in S-ARF patients except those admitted to CCU, and those took a high-dose aspirin or did not receive IMV. The protective effect of aspirin may be mediated by a low dynamic level of NLR and a high dynamic level of Cdyn and WMP. The findings should be interpreted cautiously, given the sample size and potential for residual confounding.

Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE. In addition, the experimental approaches used in IE research to improve the understanding of disease mechanisms and the current diagnostic pipelines are discussed, as well as potential innovative diagnostic and therapeutic strategies. This will ultimately help towards deriving better diagnostic tools and treatments to improve IE patient outcomes.

The incidence of infective endocarditis (IE) is increasing worldwide, resulting in a higher number of patients with IE being admitted to intensive care units (ICU). Nearly half of patients with IE develop a complication during their clinical course. However, few well conducted studies or reviews are devoted to critically ill IE patients. This review discusses the contemporary perioperative and intensive care literature.

IE epidemiology is changing towards elderly and frail patients. ICU patients are at risk of risk of developing IE because they are often in a pro-inflammatory state and many also have several indwelling catheters, which favors infection. Increased performance and recent advances in cardiac imaging allow for easier diagnosis of EI, but the applicability of these techniques to ICU patients is still relatively limited. New developments in antibiotic treatment and adjunctive therapies are explored further in this review.

The lack of evidence on ICU patients with IE highlights the critical importance of multidisciplinary decision-making and the need for further research.

Infective endocarditis remains an illness that carries a significant burden to healthcare resources. In recent times, there has been a shift from Streptococcus sp. to Staphylococcus sp. as the primary organism of interest. This has significant consequences, given the virulence of Staphylococcus and its propensity to form a biofilm, rendering non-surgical therapy ineffective. In addition, antibiotic resistance has affected treatment of this organism. The cohorts at most risk for Staphylococcal endocarditis are elderly patients with multiple comorbidities. The innovation of transcatheter technologies alongside other cardiac interventions such as implantable devices has contributed to the increased risk attributable to this cohort. We examined the pathophysiology of infective endocarditis carefully. Inter alia, the determinants of Staphylococcus aureus virulence, interaction with host immunity, as well as the discovery and emergence of a potential vaccine, were investigated. Furthermore, the potential role of prophylactic antibiotics during dental procedures was also evaluated. As rates of transcatheter device implantation increase, endocarditis is expected to increase, especially in this high-risk group. A high level of suspicion is needed alongside early initiation of therapy and referral to the heart team to improve outcomes.