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A quarter of patients with implanted cardiac devices have a patent foramen ovale (PFO). Thrombus is frequently noted on intravascular leads that in the presence of a PFO could result in cerebral vascular embolic events. However, whether this mechanism of stroke occurs is not clearly known. We report three patients with PFO, implanted leads with thrombus, and stroke, including a patient where thrombus partially attached to the lead was seen traversing the PFO. [ABSTRACT FROM AUTHOR]

Objective: Patients with bicuspid aortic valves (BAV) are at increased risk of infective endocarditis (IE). Information of the clinical presentation and the microbiology of BAV-associated IE, however, is limited. Therefore, our study aimed to characterise the clinical features native valve endocarditis (NVE) in the setting of BAV and compared them to patients with prosthetic valve endocarditis (PVE) following BAV replacement., Methods: Adult patients with BAV or history of BAV with aortic valve replacement (AVR) and a definite or possible IE diagnosis within the Mayo Clinic Enterprise (USA) from January 2008 to December 2021, were included. BAV was confirmed by trans-oesophageal echocardiography. IE was defined according to the modified Duke criteria and only an initial episode was included. Statistical analyses were performed to compare clinical characteristics, microbiology, and IE complications., Results: Overall, 161 patients with BAV and IE (NVE [n=60], 37.3%) and PVE [n=101, 62.7%) were included. Mean age±SD was 56.5±16.1 years, and 139 (86.3%) patients were males. PVE patients were older (p<0.01) and had a higher rate of hypertension (p<0.01), chronic heart failure (p<0.01), chronic kidney disease (p<0.01), and perivalvular abscess (p<0.01). BAV patients with NVE had a higher prevalence of isolated mitral valve IE (p<0.01), moderate to severe aortic valve regurgitation (p<0.01) and combined aortic with mitral valve IE (p<0.01). Streptococcus mitis was the most common pathogen in NVE (30.0%) while Staphylococcus aureus was the most common in PVE (15.8%)., Conclusions: Patients with BAV are at risk of both NVE and PVE. Each syndrome has unique clinical features, including microbiologic findings, that should be appreciated in IE diagnosis and management., Competing Interests: Disclosures L.M.B. reports UpToDate, royalty payments (authorship duties); Boston Scientific, consultant duties; and philanthropic funding from Eva and Gene Lane. The other authors had no disclosures or conflicts of interest., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Cardiac implantable electronic device infection in the context of corynebacterial bloodstream infection (BSI) remains poorly understood. From 2012 to 2023 at Mayo Clinic, 4 of 12 patients with corynebacterial BSI had cardiac implantable electronic device infection: 1 patient was diagnosed during a relapsing BSI episode. Undefined source, persistent BSI, and the presence of a prosthetic cardiac valve were common characteristics., Competing Interests: Potential conflicts of interest. L. M. B.: UpToDate, Inc (royalty payments–authorship duties), Boston Scientific (consultant duties). M. R. S.: Medtronic (research funding, honoraria/consulting fees), Philips (honoraria/consulting fee), AngioDynamics (honoraria/consulting fee). B. R. P.: Armor Health (consulting fee). M. M.: CERTITUDE registry, BIOTRONIK Inc (steering committee member); Boston Scientific (research funding). All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: We performed a cross-sectional study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyze the trends in cardiac implantable electronic device (CIED) infection-related mortality from 1999 to 2020., Methods: We analyzed the death certificate data from the CDC WONDER database from 1999 to 2020 for CIED infections in the US population aged ≥25 years using International Classification of Diseases, Tenth Revision (ICD-10) codes, listed as the underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual mortality trends, we employed the Joinpoint regression model, calculating the annual percent change (APC) in AAMR and corresponding 95% CIs., Results: Overall, there was an observed declining trend in AAMRs related to CIED infection-related mortality. Males accounted for 55% of the total deaths, with persistently higher AAMRs compared to females over the study duration. Both males and females had an overall decreasing trend in AAMRs throughout the study duration. On race/ethnicity stratified analysis, non-Hispanic (NH) Blacks exhibited the highest overall AAMR, followed by NH American Indians or Alaska Natives, NH Whites, Hispanic or Latinos, and NH Asian or Pacific Islanders. On a stratified analysis based on region, the South region had the highest overall AAMR, followed by the Midwest, West, and Northeast regions., Conclusion: Our study demonstrates a significant decline in CIED infection-related mortality in patients over the last two decades. Notable gender, racial/ethnic, and regional differences exist in the rates of mortality related to CIED infections., (© 2024 Wiley Periodicals LLC.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest . L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest. L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) encompasses a range of clinical syndromes, including valvular, device lead, and bloodstream infections. However, accurately diagnosing CIED-IE remains challenging owing in part to diverse clinical presentations, lack of standardized definition, and variations in guideline recommendations. Furthermore, current diagnostic modalities, such as transesophageal echocardiography and [ 18 F]-fluorodeoxyglucose positron emission tomography-computed tomography have limited sensitivity and specificity, further contributing to diagnostic uncertainty. This can potentially result in complications and unnecessary costs associated with inappropriate device extraction. Six hypothetical clinical cases that exemplify the diverse manifestations of CIED-IE are addressed herein. Through these cases, we highlight the importance of optimizing diagnostic accuracy and stewardship, understanding different pathogen-specific risks for bloodstream infections, guiding appropriate device extraction, and preventing CIED-IE, all while addressing key knowledge gaps. This review both informs clinicians and underscores crucial areas for future investigation, thereby shedding light on this complex and challenging syndrome., Competing Interests: Funding Support and Author Disclosures Dr Baddour has received royalty payments from and served authorship duties for UpToDate; and has served as a consultant for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Given the challenges of conventional therapies in managing right-sided infective endocarditis (RSIE), percutaneous mechanical aspiration (PMA) of vegetations has emerged as a novel treatment option. Data on trends, characteristics, and outcomes of PMA, however, have largely been limited to case reports and case series., Aims: The aim of the current investigation was to provide a descriptive analysis of PMA in the United States and to profile the frequency of PMA with a temporal analysis and the patient cohort., Methods: The International Classification of Diseases, 10th Revision codes were used to identify patients with RSIE in the national (nationwide) inpatient sample (NIS) database between 2016 and 2020. The clinical characteristics and temporal trends of RSIE hospitalizations in patients who underwent PMA was profiled., Results: An estimated 117,955 RSIE-related hospital admissions in the United States over the 5-year study period were estimated and 1675 of them included PMA. Remarkably, the rate of PMA for RSIE increased 4.7-fold from 2016 (0.56%) to 2020 (2.62%). Patients identified with RSIE who had undergone PMA were young (medial age 36.5 years) and had few comorbid conditions (median Charlson Comorbidity Index, 0.6). Of note, 36.1% of patients had a history of hepatitis C infection, while only 9.9% of patients had a cardiovascular implantable electronic device. Staphylococcus aureus was the predominant (61.8%) pathogen. Concomitant transvenous lead extraction and cardiac valve surgery during the PMA hospitalization were performed in 18.2% and 8.4% of admissions, respectively. The median hospital stay was 19.0 days, with 6.0% in-hospital mortality., Conclusions: The marked increase in the number of PMA procedures in the United States suggests that this novel treatment option has been embraced as a useful tool in select cases of RSIE. More work is needed to better define indications for the procedure and its efficacy and safety., (© 2024 Wiley Periodicals LLC.)

The American Heart Association sponsored the first iteration of a scientific statement that addressed all aspects of cardiovascular implantable electronic device infection in 2010. Major advances in the prevention, diagnosis, and management of these infections have occurred since then, necessitating a scientific statement update. An 11-member writing group was identified and included recognized experts in cardiology and infectious diseases, with a career focus on cardiovascular infections. The group initially met in October 2022 to develop a scientific statement that was drafted with front-line clinicians in mind and focused on providing updated clinical information to enhance outcomes of patients with cardiovascular implantable electronic device infection. The current scientific statement highlights recent advances in prevention, diagnosis, and management, and how they may be incorporated in the complex care of patients with cardiovascular implantable electronic device infection.

There have been no published prospective randomized clinical trials that have: (1) established an association between invasive dental and nondental invasive procedures and risk of infective endocarditis; or (2) defined the efficacy and safety of antibiotic prophylaxis administered in the setting of invasive procedures in the prevention of infective endocarditis in high-risk patients. Moreover, previous observational studies that examined the association of nondental invasive procedures with the risk of infective endocarditis have been limited by inadequate sample size. They have typically focused on a few potential at-risk surgical and nonsurgical invasive procedures. However, recent investigations from Sweden and England that used nationwide databases and demonstrated an association between nondental invasive procedures, and the subsequent development of infective endocarditis (in particular, in high-risk patients with infective endocarditis) prompted the development of the current science advisory.

Background: Shotgun and targeted metagenomic sequencing have been shown in separate studies to be potentially useful for culture-free pathogen identification in blood and/or plasma of patients with infective endocarditis (IE). However, the 2 approaches have not been directly compared. The aim of this study was to compare shotgun metagenomic sequencing with targeted metagenomic sequencing (tMGS) for organism identification in blood or plasma of patients with IE., Methods: Patients with possible or definite IE were prospectively enrolled from October 2020 to July 2021. Shotgun metagenomic sequencing was performed with the Karius test, which uses microbial cell-free DNA (mcfDNA) sequencing to detect, identify, and quantitate DNA-based pathogens in plasma. tMGS was performed using a 16S ribosomal RNA (rRNA) polymerase chain reaction assay targeting the V1 to V3 regions of the 16S rRNA gene. Results were compared using the McNemar test of paired proportions., Results: Samples from 34 patients were investigated. The Karius test was positive in 24/34 (71%), including 3/6 (50%) with blood culture-negative endocarditis (BCNE), which was not significantly different from the positivity rate of tMGS ( P = .41). Results of the Karius test were concordant with tMGS in 75% of cases. The Karius test detected 2 cases of methicillin-resistant Staphylococcus aureus among the 7 S. aureus detections, in accordance with results of phenotypic susceptibility testing. The combination of blood cultures, the Karius test, and tMGS found a potential causative pathogen in 33/34 (97%), including 5/6 with BCNE., Conclusions: The Karius test and tMGS yielded comparable detection rates; however, beyond organism identification, the Karius test generated potentially useful antibiotic resistance data., Competing Interests: Potential conflicts of interest. L.F., C.R.F., and M.W. have no conflicts of interest. R.P. reports grants from ContraFect, TenNor Therapeutics Limited, and BioFire. R.P. is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Day Zero Diagnostics, Mammoth Biosciences, and Qvella; monies are paid to Mayo Clinic. Mayo Clinic and Dr. Patel have relationships with Adaptive Phage Therapeutics and Pathogenomix. R.P. is also a consultant to Netflix and CARB-X. In addition, R.P. has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued. R.P. receives honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort., Methods: The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality., Results: During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%-6.4%), with rates of 4.0% (95% CI, 1.8%-6.2%) in the EVAR group and 5.8% (95% CI, 2.9%-8.6%) in the OSR group ( P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases ( P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%-34.0%), 55.8% (95% CI, 32.1%-71.2%), and 76.8% (95% CI, 44.3%-90.3%), respectively., Conclusions: The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort., Competing Interests: Potential conflicts of interest. L. M. B. has received royalty payments (authorship duties) from UpToDate and has served as a consultant for Boston Scientific. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease ( p = 0.002) and a foreign cardiovascular material ( p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS ( p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis , confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Objective: To describe the incidence, epidemiology, and outcomes of vascular graft infection (VGI) in a population-based study in southern Minnesota., Patients and Methods: Retrospective review of all adult patients from 8 counties who underwent arterial aneurysm repair between January 1, 2010, and December 31, 2020. Patients were identified through the expanded Rochester Epidemiology Project. The Management of Aortic Graft Infection Collaboration criteria were used to define VGI., Results: A total of 643 patients underwent 708 aneurysm repairs: 417 endovascular (EVAR) and 291 open surgical (OSR) repairs. Of these patients, 15 developed a VGI during median follow-up of 4.1 years (interquartile range, 1.9-6.8 years), corresponding to a 5-year cumulative incidence of 1.6% (95% CI, 0.6% to 2.7%). The cumulative incidence of VGI 5 years after EVAR was 1.4% (95% CI, 0.2% to 2.6%) compared with 2.0% (95% CI, 0.3% to 3.7%) after OSR (P=.843). Of the 15 patients with VGI, 12 were managed conservatively without explantation of the infected graft/stent. Ten died during median follow-up from VGI diagnosis of 6.0 years (interquartile range, 5.5-8.0 years), including 8 of the 12 patients treated conservatively., Conclusion: The VGI incidence in this study was overall low. There was no statistically significant difference in VGI incidence after OSR and EVAR. The all-cause mortality rate after VGI was high and reflected an older cohort with multiple comorbid conditions., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Bloodstream infection (BSI) in patients with cardiac implantable electronic devices (CIEDs) is common and can prompt challenges in defining optimal management. We provide a contemporary narrative review of this topic and propose a pathogen-dependent clinical approach to patient management., Recent Findings: BSI due to staphylococci, viridans group streptococci, and enterococci is associated with an increased risk of underlying CIED infection, while the risk of CIED infection due to other organisms is poorly defined. There is growing evidence that positron emission tomography-computed tomography may be helpful in some patients with BSI and underlying CIED. Twenty studies were included to examine the impact of microbiologic findings on the risk of CIED infection among patients with BSI. Diagnosis of CIED infection in patients with BSI without pocket findings is often difficult, necessitating the use of novel diagnostic tools to help guide the clinician in subsequent patient management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The influence of different bicuspid aortic valve (BAV) morphology in the clinical course of infective endocarditis (IE) has not yet been investigated. This study aimed to describe the clinical and echocardiographic features of IE in patients with BAV (BAVIE) according to valve morphology., Methods: Patients with definite BAVIE prospectively enrolled in 4 high-volume referral centers from 2000 to 2019 were evaluated and divided into 2 groups according to the echocardiographic definition of fused BAV morphology: right-left coronary (RL type) and right noncoronary or left noncoronary (non-RL type) cusp fusion. All patients were followed up for 1 year., Results: One hundred thirty-eight patients with BAVIE were included (77.7% male; median age, 52 [36.83-61.00] years): 112 patients with RL type (81%) and 26 patients with non-RL type BAV (19%), with no significant differences in age, sex, and comorbidities between groups. Although 43% of the cohort had known BAV, the referral was late after symptom onset, particularly for the RL phenotype; time from symptom onset to hospitalization >30 days (31.3% vs 11.5%; P = .032) and New York Heart Association class ≥ II (64.3% vs 42.3%; P = .039) were more frequent in patients with RL type BAV than in patients with non-RL type BAV. Conversely, patients with non-RL type BAV had a higher incidence of hemorrhagic stroke (19.2% vs 5.4%; P = .034) and high-grade atrioventricular block (11.5% vs 0.9%; P = .021). Streptococcus viridans was more frequently isolated in patients with non-RL type BAV than in patients with RL type BAV (44% vs 24.1%; P = .045). No difference in short- and intermediate-term mortality was observed between groups., Conclusions: Clinical profile and echocardiographic features in BAVIE patients may differ according to valve morphology, and patients with BAVIE appear to be referred late, even when BAV disease is previously known., (Copyright © 2023 American Society of Echocardiography. All rights reserved.)

Background: In contrast to bloodstream infection due to a variety of bacteria in patients with cardiovascular implantable electronic devices (CIED), there are limited data regarding candidemia and risk of CIED infection., Methods: All patients with candidemia and a CIED at Mayo Clinic Rochester between 2012 and 2019 were reviewed. Cardiovascular implantable electronic device infection was defined by (1) clinical signs of pocket site infection or (2) echocardiographic evidence of lead vegetations., Results: A total of 23 patients with candidemia had underlying CIED; 9 (39.1%) cases were community onset. None of the patients had pocket site infection. The duration between CIED placement and candidemia was prolonged (median 3.5 years; interquartile range, 2.0-6.5). Only 7 (30.4%) patients underwent transesophageal echocardiography and 2 of 7 (28.6%) had lead masses. Only the 2 patients with lead masses underwent CIED extraction, but device cultures were negative for Candida species. Two (33.3%) of 6 other patients who were managed as candidemia without device infection subsequently developed relapsing candidemia. Cardiovascular implantable electronic device removal was done in both patients and device cultures grew Candida species. Although 17.4% of patients were ultimately confirmed to have CIED infection, CIED infection status was undefined in 52.2%. Overall, 17 (73.9%) patients died within 90 days of diagnosis of candidemia., Conclusions: Although current international guidelines recommend CIED removal in patients with candidemia, the optimal management strategy remains undefined. This is problematic because candidemia alone is associated with increased morbidity and mortality as seen in this cohort. Moreover, inappropriate device removal or retention can both result in increased patient morbidity and mortality., Competing Interests: Potential conflicts of interest. LMB reports the following: royalty payments—authorship duties from UpToDate, Inc.; consultant duties for Boston Scientific; and consultant duties for Roivant Sciences. MRS reports the following: research funding and honoraria/consulting fees from Medtronic; and honoraria/consulting fee from Spectranetics, Boston Scientific, and Philips. BRP reports consulting fees from Armor Health. MM reports the following: consulting for Convatec, Biotronik Inc., and Biosense Webster; and research funding from Boston Scientific. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE., Methods: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups., Results: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates., Conclusion: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification., Competing Interests: Declarations of competing interest Dr Larry M Baddour: UpToDate, Inc. – royalty payments (authorship duties); Boston Scientific - consultant duties; Roivant Sciences - consultant duties. The other authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P  = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P  = 0.86) or cefazolin (10.3% versus 11.9%, P  = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Objectives: To provide an evaluation of predictors of 6-month mortality in incident Staphylococcus aureus bacteraemia cases., Methods: A retrospective population-based study of 541 adult residents of Olmsted County, MN with monomicrobial S. aureus bacteraemia from 1 January 2006 through 31 December 2020. Multivariable Cox regression was used to investigate risk factors of 6-month mortality., Results: The median (interquartile range [IQR]) age of 541 patients with S. aureus bacteraemia was 66.8 (54.4-78.5) years and 39.6% were female. The median (IQR) Charlson Comorbidity Index was 6 (3-9). Overall, 144 patients died during the six-month period following their initial episode (30-day and 6-month mortality = 16.5% and 26.7%, respectively). In a multivariable analysis, older age, ICU admission, and unknown source of infection were significant predictors of increased 6-month mortality. In contrast, having an infectious diseases (ID) consultation was associated with reduced mortality in the first 2 weeks of follow-up. Secondary analyses revealed an early benefit of ID consultation during the first 30 days of follow-up and that infective endocarditis was an additional predictor of 6-month mortality., Conclusions: To our knowledge, this investigation represents the only US population-based study evaluating predictors of mortality in patients with S. aureus bacteraemia. The finding of a short-term survival benefit associated with early ID consultation may be due to more extensive diagnostic efforts.

Background: Deep brain stimulator (DBS)-related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections., Methods: This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester., Results: There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9-6.9) months. The odds of infection were higher with longer operative length ( P = .002), higher body mass index (BMI; P = .006), male sex ( P = .041), and diabetes mellitus ( P = .002). The association between infection and higher BMI ( P = .002), male sex ( P = .016), and diabetes mellitus ( P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation ( P = .015). Only 1 individual had complications with brain abscess at failure., Conclusions: Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications., Competing Interests: Potential conflicts of interest. Hussam Tabaja: no conflict. Jason Yuen: no conflict. Don Bambino Geno Tai: no conflict. Cristina Corsini Campioli: no conflict. Supavit Chesdachai: no conflict. Daniel C. DeSimone: no conflict. Anhar Hassan: no conflict. Bryan T. Klassen: no conflict. Kai J. Miller: no conflict. Kendall H. Lee: stockholder and board member of NaviNetics. Maryam Mahmood: no conflict. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cardiovascular implantable electronic device (CIED) infection carries significant morbidity and mortality with bacteremia being a possible marker of device infection. A clinical profile of non- Staphylococcus aureus gram-positive cocci (non-SA GPC) bacteremia in patients with CIED has been limited., Objective: To examine characteristics of patients with CIED who developed non-SA GPC bacteremia and risk of CIED infection., Methods: We reviewed all patients with CIED who developed non-SA GPC bacteremia at the Mayo Clinic between 2012 and 2019. The 2019 European Heart Rhythm Association Consensus Document was used to define CIED infection., Results: A total of 160 patients with CIED developed non-SA GPC bacteremia. CIED infection was present in 90 (56.3%) patients, in whom 60 (37.5%) were classified as definite and 30 (18.8%) as possible. This included 41 (45.6%) cases of coagulase-negative Staphylococcus (CoNS), 30 (33.3%) cases of Enterococcus , 13 (14.4%) cases of viridans group streptococci (VGS), and 6 (6.7%) cases of other organisms. The adjusted odds of CIED infection in cases due to CoNS, Enterococcus , and VGS bacteremia were 19-, 14-, and 15-fold higher, respectively, as compared with other non-SA GPC. In patients with CIED infection, the reduction in risk of 1-year mortality associated with device removal was not statistically significant (hazard ratio 0.59; 95% confidence interval 0.26-1.33; P = .198)., Conclusions: The prevalence of CIED infection in non-SA GPC bacteremia was higher than previously reported, particularly in cases due to CoNS, Enterococcus species, and VGS. However, a larger cohort is needed to demonstrate the benefit of CIED extraction in patients with infected CIED due to non-SA GPC., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform.

Objective: To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US)., Methods: A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups., Results: Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3-2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection ( p = 0.008) and less likely to be community-acquired cases ( p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12-3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96-3.87, p = 0.064)., Conclusions: To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases.

Objective: To estimate the incidence of invasive pneumococcal disease (IPD) in the pre-13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods., Patients and Methods: Using the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018., Results: Overall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non-7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%)., Conclusion: A marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: The American Heart Association has sponsored both guidelines and scientific statements that address the diagnosis, management, and prevention of infective endocarditis. As a result of the unprecedented and increasing incidence of infective endocarditis cases among people who inject drugs, the American Heart Association sponsored this original scientific statement. It provides a more in-depth focus on the management of infective endocarditis among this unique population than what has been provided in prior American Heart Association infective endocarditis-related documents., Methods: A writing group was named and consisted of recognized experts in the fields of infectious diseases, cardiology, addiction medicine, and cardiovascular surgery in October 2021. A literature search was conducted in Embase on November 19, 2021, and multiple terms were used, with 1345 English-language articles identified after removal of duplicates., Conclusions: Management of infective endocarditis in people who inject drugs is complex and requires a unique approach in all aspects of care. Clinicians must appreciate that it requires involvement of a variety of specialists and that consultation by addiction-trained clinicians is as important as that of more traditional members of the endocarditis team to improve infective endocarditis outcomes. Preventive measures are critical in people who inject drugs and are cured of an initial bout of infective endocarditis because they remain at extremely high risk for subsequent bouts of infective endocarditis, regardless of whether injection drug use is continued.

Initial microbiologic diagnosis of infective endocarditis (IE) relies on blood cultures and Bartonella and Coxiella burnetii serology. Small case series and one prospective study have preliminarily reported application of metagenomic sequencing on blood or plasma for IE diagnosis. Here, results of a prospective pilot study evaluating targeted metagenomic sequencing (tMGS) for blood-based early pathogen detection and identification in IE are reported. Subjects diagnosed with possible or definite IE at a single institution were prospectively enrolled with informed consent from October 2020 to July 2021. Blood was drawn and separated into whole blood and plasma. Both specimen types were subjected to nucleic acid extraction and PCR targeting the V1-V3 region of the 16S ribosomal RNA gene, followed by next-generation sequencing on an Illumina MiSeqTM platform. 35 subjects, 28 (80%) with definite and 7 (20%) with possible IE were enrolled, including 6 (17%) with blood culture-negative endocarditis (BCNE). Overall, 20 whole blood (59%) and 16 plasma (47%) samples tested positive ( P  = 0.47). When results of whole blood and plasma testing were combined, a positive tMGS result was found in 23 subjects (66%). tMGS identified a potential pathogen in 5 of 6 culture-negative IE cases. Although further study is needed, the results of this pilot study suggest that blood-based tMGS may provide pathogen identification in subjects with IE, including in culture-negative cases.

Background: Gram-negative bacteremia (GNB) as a manifestation of cardiovascular implantable electronic device (CIED) infection is uncommon. Moreover, echocardiography may be nonspecific in its ability to differentiate whether CIED lead masses are infected. We aimed to determine the rate of CIED infection in the setting of GNB., Methods: All patients with CIED who were hospitalized with GNB during 2012-2019 at Mayo Clinic were investigated. The definition of CIED infection was based on criteria recommended by the 2019 European Heart Rhythm Association document., Results: A total of 126 patients with CIED developed GNB. None of them had signs of pocket infection. Twenty (15.9%) patients underwent transesophageal echocardiography. Overall, 4 (3%) patients had definite CIED infection. None of them underwent CIED extraction; 3 died within 12 weeks and 1 received long-term antibiotic suppression. Ten (8%) patients had possible CIED infection; despite no CIED extraction, no patient had relapsing GNB. We observed a higher rate of CIED infection in patients with Serratia marcescens bacteremia as compared to that in patients with other GNB., Conclusions: The rate of CIED infection following GNB was relatively low. However, accurate classification of CIED infection among patients presenting with GNB remains challenging, in part, due to a case definition of CIED infection that is characterized by a low pretest probability in the setting of GNB. Prospective, multicenter studies are needed to determine accurate identification of CIED infection among GNB, so that only patients with true infection undergo device removal., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Pyogenic brain abscess poses a significant management challenge to clinicians, hence early diagnosis and interventions are critical. Our objective was to assess predictors of failure of therapy among patients with pyogenic brain abscesses according to surgical versus medical treatment., Methods: Retrospectively reviewed adults with pyogenic brain abscesses at our institution between 2009 and 2020. Treatment was classified as early surgical intervention and no early surgical treatment (medical therapy). Propensity score (PS) adjustment and multivariable regression were used to assess risk of treatment failure from surgical intervention and baseline covariates., Results: A total of 224 patients had pyogenic brain abscess, of whom 106 (47.3%) had early surgical treatment and 118 (52.7%) had medical treatment only. Significant predictors of surgical (vs. medical) treatment included essential hypertension (odds ratio [OR] 95% confidence interval [95% CI] = 2.06 [1.01-4.18]), abscesses number (single vs. multiple, OR [95% CI] =4.81 [1.64-14.08]), midline shift (OR [95% CI] = 3.09 [1.22-7.82]). At 6 months, treatment failure cumulative incidence was 27.1% in the medical group (n = 31) and 21.3% in early surgical group (n = 22). PS-adjusted analysis showed beneficial effect of early surgical treatment (hazard ratio [HR] [95% CI] = 0.55 [0.31-0.98]). Multivariable regression showed similar but statistically nonsignificant estimate of surgical benefit (HR [95% CI] =0.59 [0.34-1.01]; P  = 0.056), and significant associations of Charlson Comorbidity Index (CCI) ( P  = 0.019) and pre-existing central nervous system hardware ( P  = 0.034) with increased risk of treatment failure., Conclusions: Higher CCI and pre-existing CNS hardware were significant risk factors associated with treatment failure. In propensity-adjusted analysis, early surgery was associated with a 45% reduction in risk of 6-month treatment failure., Competing Interests: J.C.O. has received consulting fees from Bates College and Elsevier Inc. not related to the present work. LM.B. has received royalty payments (authorship duties) from UpToDate, Inc., and consulting fees from Boston Scientific, and Roivant Sciences over the past 12 months. MR.S.: Honoraria/Consulting fee: Medtronic Inc., Philips, and Aziyo Biologics, Inc. (All < US$10K). Research Grant: 10.13039/100004374Medtronic (all unrelated to current research). J.J.V.G. has no conflicts related to this research however is named inventor for intellectual property licensed to Cadence Neuroscience Inc, which is co-owned by Mayo Clinic. BNL has waived contractual rights to royalties. J.J.V.G. is an investigator for the Medtronic Deep Brain Stimulation Therapy for Epilepsy Post-Approval Study (EPAS) as well as Mayo Clinic Medtronic NIH Public Private Partnership (UH3-NS95495). All other authors: None., (© 2022 The Author(s).)

Background: There is insufficient evidence regarding postoperative systemic antibiotic prophylaxis use for more than 24 h following cardiovascular implantable electronic devices (CIED) implantation and its impact on infection prevention. However, this strategy remains a common practice in many institutions., Methods: We conducted a systematic review and meta-analysis including studies that compared the outcomes of patients: (1) who received preoperative plus 24 h or more of postoperative antibiotic prophylaxis (intervention group); and (2) who received either preoperative only or preoperative plus less than 24 h of antibiotic prophylaxis (control group). Risk of bias was assessed with ROBINS-I and ROB-2 tools. Risk ratio (RR) was pooled using random-effect meta-analyses with inverse variance method., Results: Eight studies that included two randomized controlled trials (RCTs) and six cohort studies with a total of 26,187 patients were included in the analysis. Overall, there were no differences in outcomes between the two groups, which included rates of CIED infection (RR 0.77, 95% CI 0.42, 1.42), mortality (RR 1.19, 95% CI 0.69, 2.06), pocket hematoma (RR 1.15, 95% CI 0.44, 3.00) or reintervention (RR 0.87, 95% CI 0.22, 3.46). Of note, the results were primarily impacted by the larger RCT., Conclusions: There was no benefit of postoperative antibiotic prophylaxis for more than 24 h following CIED implantation in the current systematic review and meta-analysis. This supports the practice advocated by current guidelines which foster antibiotic stewardship and may result in reductions of adverse drug events, selection for antibiotic resistance, and financial costs of prolonged postoperative antibiotic prophylaxis., (© 2022 Wiley Periodicals LLC.)

Objectives: Spinal cord stimulation (SCS) is considered a minimally invasive and reversible neuromodulation therapy for various chronic pain disorders. The rates of infection following SCS surgery reported in the literature range from 2.8% to 10%. Several studies indicated no potential benefit of postoperative antibiotics (beyond 24 hours) on subsequent device infection. This study aimed to understand the characteristics of postoperative antibiotic prescriptions and subsequent infections following SCS surgery., Materials and Methods: The study was a retrospective cohort using the IBM® MarketScan® Commercial and Medicare Supplemental Databases from 2013 to 2018. Adult patients undergoing SCS surgical procedures with at least 90 days of follow-up were identified using Current Procedural Terminology (CPT®) codes. Postprocedural oral antibiotics within 14 days and preprocedural corticosteroid use within seven days were identified using National Drug Codes (NDC). Administrative claims were analyzed to understand the characteristics of prescribed postoperative antibiotics. Infection-related complications within 90 days were identified using administrative codes., Results: A total of 18,105 patients (age 55.5 ± 13.1 years, 40.2% male) underwent SCS surgery during the study period. Postprocedural oral antibiotics and preprocedural steroids were prescribed for 35.3% and 2.6%, respectively, for SCS surgery patients. The most commonly used postprocedural antibiotics were cephalexin (55.4%) and sulfamethoxazole-trimethoprim (10.6%). The most common duration of antibiotic prescriptions was seven, ten, and five days in our study, from most to least common duration. Superficial surgical site infection (SSI), deep SSI, device infection, or any infection within 90 days occurred in 2.9%, 1.0%, 1.8%, and 4%, respectively, of the patients undergoing SCS surgery., Conclusions: Prospective studies are needed to understand the reasons for noncompliance with expert consensus recommendations on postoperative antibiotic use beyond 24 hours of SCS surgery. Neuromodulation team members should play an important role in antibiotic stewardship., (Copyright © 2021 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients., Methods: Our search was conducted in 8 databases for all published reports of probable or definite IE in patients with a prior COVID-19 confirmed diagnosis. After ensuring an appropriate inclusion of the articles, we extracted data related to clinical characteristics, modified duke criteria, microbiology, outcomes, and procedures., Results: Searches generated a total of 323 published reports, and 20 articles met our inclusion criteria. The mean age of patients was 52.2 ± 16.9 years and 76.2% were males. Staphylococcus aureus was isolated in 8 (38.1%) patients, Enterococcus faecalis in 3 patients (14.3%) and Streptococcus mitis/oralis in 2 (9.5%) patients. The mean time interval between COVID-19 and IE diagnoses was 16.7 ± 15 days. Six (28.6%) patients required critical care due to IE, 7 patients (33.3%) underwent IE-related cardiac surgery and 5 patients (23.8%) died during their IE hospitalization., Conclusions: Our systematic review provides a profile of clinical features and outcomes of patients with a prior COVID-19 infection diagnosis who subsequently developed IE. Due to the ongoing COVID-19 pandemic, it is essential that clinicians appreciate the possibility of IE as a unique complication of COVID-19 infection., Competing Interests: Conflicts of interest Larry M. Baddour, M.D. reports UpToDate, royalty payments (authorship duties); Boston Scientific, consultant duties; Botanix Pharmaceuticals, consulting duties; Roivant Sciences Inc., consultant duties. None of the other authors had disclosures., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine incidence trends of Staphylococcus aureus bacteremia (SAB) from population-based studies from multiple countries., Methods: A contemporary systematic review was conducted using Ovid Cochrane Central Register of Controlled Trials (1991+), Ovid Embase (1974+), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE) (1946+ including epub ahead of print, in-process & other non-indexed citations), and Web of Science Core Collection (Science Citation Index Expanded 1975+ and Emerging Sources Citation Index 2015+). Two authors (J.R.H. and J.A.Q.M.) independently reviewed all studies and included those that reported population-based incidence of SAB in patients aged 18 years and older., Results: Twenty-six studies met inclusion criteria with the highest number (n=6) of studies conducted in Canada. The incidence of SAB ranged from 9.3 to 65 cases/100,000/year. The median age of patients with SAB ranged from 62 to 72 years and SAB cases were more commonly observed in men than in women. The most common infection sources were intravascular catheters and skin and soft tissue infections. SAB incidence trends demonstrated high variability for geographic regions and calendar years. Overall, there was no change in the incidence trend across all studies during the past two decades., Conclusion: Multiple factors, both pros, and cons are likely responsible for the overall stable SAB incidence in countries included in this systematic review. Some of these factors vary in geographic location and prompt additional investigations from countries not included in the current review so that a more global characterization is defined., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Hindy et al.)

Objective: Non-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients., Methods: Adults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up., Results: Forty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively)., Conclusions: NBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality., Competing Interests: Competing interests: LMB reports the following: UpToDate, royalty payments (authorship duties); Boston Scientific, consultant duties; Botanix Pharmaceuticals, consulting duties; Roivant Sciences, consultant duties. None of the other authors had disclosures., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020., Methods: This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester., Results: Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4-78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0-36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0-51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1-27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period ( P  = .093)., Conclusions: Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past 2 decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED, and determination of device infection often is difficult., Objectives: The purpose of this study was to examine the rate and clinical characteristics of SAB in patients living with CIED using the 2019 European Heart Rhythm Association (EHRA) international consensus document., Methods: We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from 2012 to 2019. Patients who met CIED infection criteria after SAB based on EHRA criteria were identified. A descriptive statistic and time-dependent Cox model were used., Results: Overall, 110 patients with CIED developed SAB, of whom 92 (83.6%) underwent transesophageal echocardiogram (TEE). Fifty-seven (51.8%) and 31 (28.2%) patients met criteria for definite and possible CIED infections, respectively. At 30-day follow-up, the cumulative rate of patients undergoing complete device extraction was 80.0% in the definite CIED infection group, compared with 38.8% and 32.9% in the possible and rejected CIED infection groups, respectively. We found that CIED extraction was associated with an 83% reduction in risk of 1-year mortality in the definite CIED infection group., Conclusion: The rate of CIED infections after SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria likely were operative, in part, in accounting for the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with definite CIED infection to improve 1-year mortality., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Differences in management and outcomes of brain abscesses due to gram-positive (GPB) versus gram-negative bacteria (GNB) are not well defined., Methods: A retrospective review of adult patients with brain abscesses due to monomicrobial infection from 2009 through 2020 was performed., Results: A total 177 patients had a monomicrobial brain abscess; 143 (80.8%) caused by GPB and 34 (19.2%) by GNB. Patients with GNB had more history of head/neck surgery than those with GPB (58.8% vs 36.4%; P = 0.02). Pathogens in the GNB group included Pseudomonas aeruginosa (29.4%), Klebsiella spp (20.6%), and Enterobacter spp (20.6%). Pathogens in the GPB group included Staphylococcus aureus (32.2%) and Streptococcus spp (31.5%). Most patients had combined medical/surgical management (64.7% GNB vs 63.6% GPB). The median duration of antibiotic therapy was 42 days, and there was no significant difference in infection relapse or 3-month survival rate. Patients with GNB were more likely to have therapeutic failure than those with GPB (44.1% vs 22.4%; P = 0.01)., Conclusions: Compared with brain abscesses caused by GPB, those due to GNB were more likely to occur in patients who had undergone prior head and neck surgery . No statistically significant difference in outcomes was observed between the groups; however, patients with GNB had a higher therapeutic failure rate than those with GPB., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of this study was to determine the incidence, epidemiology, and associated risk factors of bloodstream infection (BSI) in patients who had previously undergone cardiac valve repair., Methods: A population-based study that included 7 counties in southeastern Minnesota using the expanded Rochester Epidemiology Project (e-REP) for adults (≥18 years) who underwent valve repair between 1 January 2010 and 31 December 2018 was conducted. Electronic health records were screened for development of BSI and infective endocarditis (IE) from the date of valve repair through 30 July 2020. A 1:4 nested case-control analysis was performed to determine an association, if any, of male sex, Charlson comorbidity index (CCI), and county of residence with BSI., Results: A total of 335 patients underwent valve repair, of whom 28 (8.3%) developed an index case of BSI, with 14 episodes occurring within 1 year of surgery. The median age of patients with BSI was 70 years, and 79% were male. The crude incidence of BSI was 1671 cases per 100000 person-years and Escherichia coli was the most common pathogen. Case-control analysis demonstrated a significant correlation between CCI and incidence of BSI ( P  < .001). Only 4 (14.3%) patients developed IE concurrent with the onset of BSI, and no patients developed IE subsequent to BSI., Conclusions: The crude incidence of BSI following valve repair was higher in our e-REP cohort than previous population-based studies, and half of the BSI cases occurred within 1 year of surgery. Patients with a higher CCI at baseline were at increased risk of subsequent BSI., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To evaluate incidence and risk factors of bloodstream infections (BSI) in patients with transcatheter aortic valve replacement (TAVR)., Methods: We conducted a population-based study in southeastern Minnesota using the expanded Rochester Epidemiology Project (e-REP) for all adult (≥18 years) patients who underwent TAVR from January 1, 2010 to December 31, 2018., Results: The incidence of BSI following TAVR was 1300 episodes/100,000 persons per annum. The median time to BSI following TAVR was 610 days and 84% were community-acquired. Forty percent of BSI cases developed infective endocarditis. Viridans group streptococci (VGS) were the most common pathogens and 80% of patients with VGS BSI had IE., Conclusions: The high incidence of BSI among TAVR patients is alarming and is likely due to advanced age and comorbid conditions. Because 40% of BSI patients also developed IE, further investigation of modifiable risk factors associated with BSI is warranted., Competing Interests: Declaration of competing interest Larry M. Baddour, M.D. reports UpToDate, royalty payments (authorship duties); Boston Scientific, consultant duties; Botanix Pharmaceuticals, consulting duties; Roivant Sciences Inc., consultant duties. M. Rizwan Sohail, M.D. reports receiving funds from TYRX Inc. and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic Inc., Philips, and Aziyo Biologics, Inc. Research Grant: Medtronic (significant - $40K), Honoraria: Medtronic (significant $20K), and Aziyo Biologics (modest $5K). Dr. St Sauver reports grants from National Institute on Aging, during the conduct of the study; grants from National Institute of Health and grants from Exact Sciences, outside the submitted work. The authors report no relevant conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

Despite advances in the diagnosis and management of brain abscess, significant associated morbidity and mortality remain high. We retrospectively reviewed adults who presented with pyogenic brain abscess from January 1, 2009, through June 30, 2020. Overall, 247 patients were identified. The median age was 59 years, and 33.6% had a history of head and neck surgery or traumatic brain injury. Diagnostic brain magnetic resonance imaging (MRI) was performed in the bulk (93.1%) of patients. A total of 205 patients (83%) were managed with medical and surgical treatment. The most common definitive antibiotic regimen was monotherapy (48.2%). The median duration of antimicrobial therapy was 42 days. Compared with those who received combined therapy, patients with medical therapy alone had a higher mortality rate (21.4% vs 6%; P =. 003) with more neurologic sequelae (31% vs 27.1%; P = .5). Most patients with brain abscesses are older with multiple underlying comorbidities, and one-third had antecedent head and neck surgery. A prompt combined surgical and medical approach with prolonged antimicrobial therapy may cure the infection with avoidance of permanent residual neurologic deficits., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe., Methods: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence., Results: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%., Conclusion: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase., Trial Registeration Number: CRD42020191196., Competing Interests: Competing interests: LMB, M.D. reports Boston Scientific, consultant duties; UpToDate, royalty payments (authorship duties); Botanix Pharmaceuticals, consulting duties; Roivant Sciences, consultant duties. MRS, M.D. reports receiving funds from TYRX and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic, Philips and Aziyo Biologics. Research Grant: Medtronic. MJD, M.B.B.S. reports payments from Biotronik unrelated to this study. IMT, M.D. reports UpToDate, royalty payments (authorship duties). The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)