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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.)

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.)

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.

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).)

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.)

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.)

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.)

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.)

Background: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America., Methods: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included., Results: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%., Conclusions: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG)., Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site., Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%., Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control., (Copyright © 2021. Published by Elsevier Inc.)

Background: Despite safety communications from the Food and Drug Administration (FDA) regarding the outbreak of Mycobacterium chimaera infections (MCIs) from contaminated heater-cooler devices, new cases continue to be identified., Methods: We retrospectively reviewed confirmed cases of MCI that were managed at Mayo Clinic sites (Arizona, Florida, and Minnesota) from 09/2015 to 01/2021. Clinical histories including prior cardiovascular surgery were recorded. Diagnostic workup including ophthalmologic examination, imaging, and laboratory testing was reviewed. Treatment and survival outcomes on follow-up were obtained., Results: Twelve patients with MCI were included. All patients had aortic valve or graft replacement. Five patients had their surgical procedures following the 10/15/2015 FDA safety communication. The mean time from surgery to symptom onset (range) was 32 (13-73) months. Ten of 11 patients who underwent ophthalmologic examination had chorioretinal abnormalities. Three patients who underwent microbial cell-free deoxyribonucleic acid sequencing tested positive for M. chimaera, which was subsequently confirmed with blood culture growth. Echocardiography and positron emission tomography/computed tomography (PET/CT) revealed evidence of prosthetic valve/graft infection in 7/12 (58.3%) and 6/10 (60.0%) of cases, respectively. Seven patients (58.3%) underwent redo cardiovascular surgery. Of these, 1 patient died 2 days postdischarge, 1 experienced spinal osteomyelitis relapse, and another had interval prosthetic valve fluorodeoxyglucose (FDG) uptake on PET/CT suspicious for recurrent infection. Among 4 patients on medical therapy only, 3 expired or transitioned to hospice during follow-up., Conclusions: MCI continues to occur despite the FDA communications. Incorporation of ophthalmologic examination and use of advanced tools may improve MCI diagnosis. The mortality in these patients is high even with aggressive surgical/medical management., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The Watchman device (WD) is a commonly used alternative strategy to oral anticoagulation for stroke risk reduction in patients with atrial fibrillation who have an increased bleeding risk. There are rare case reports of WD-related infection. Currently, there is no formal study that has systematically evaluated the incidence and outcomes WD-related infections. The objective of this study was to evaluate the incidence, risk factors, and outcomes for WD-associated infections in a single-center cohort over a 14-year period. All patients who underwent WD implantation over a 14-year study period (July 2004 through December 2018) comprised our cohort. Baseline characteristics, procedural data, and postimplantation events were identified through a retrospective chart review. Primary study outcomes included WD-related infection, other cardiovascular device-related infection, bacteremia, and mortality. A total of 181 patients (119 males; 65.7%) with a mean age of 75 years at implantation were included in the analysis. A total of 534.7 patient years of follow-up was accrued, with an average of 2.9 years per patient. The most common indications for implantation included gastrointestinal bleeding (56 patients; 30.9%) and intracerebral bleeding (51 patients; 28.2%). During the follow-up period, 37 (20.4%) patients died. Six developed evidence of bacteremia. Only 1 developed an implantable cardioverter defibrillator infection that required a complete system extraction. None of the cohort developed a WD-related device infection during the study period. We concluded that there is a low risk of WD-related infection even in the setting of a blood stream infection., Competing Interests: R.C.W.: Mayo Clinic, Fellow. T.M.: Mayo Clinic, Resident. F.A.: Mayo Clinic, Resident. S.P.: Creighton University, Fellow. S.J.A.: Mayo Clinic, Professor of Medicine; royalties for work licensed through the Mayo Clinic to a privately held company for contributions related to the use of nerve signal modulation to treat central, autonomic, and peripheral nervous system disorders, including pain. The Mayo Clinic received royalties from and owns equity in this company and is copatent holder for a technique to minimize coagulum formation during radiofrequency ablation. Products or techniques related to the above disclosures are not discussed in this paper. Honoraria/speaker: Atricure, Biotronik, Boston Scientific, Medtronic, Abbott, Zoll, and Johnson & Johnson. L.M.B.: Mayo Clinic, Professor Emeritus of Medicine, supplemental employee; royalty payments (authorship duties): UpToDate, Inc.; consultant duties: Boston Scientific Corp., Botanix Pharmaceuticals Inc., and Roivant Sciences Inc. D.R.H.: Mayo Clinic, Professor of Medicine. D.C.D.: Mayo Clinic, Associate Professor of Medicine. C.V.D.: Mayo Clinic, Associate Professor of Medicine., (Copyright © 2021 by S. Karger AG, Basel.)

Objective: To develop a contemporary profile of infective endocarditis (IE) among a population in 6 counties of Olmsted, Dodge, Mower, Steele, Waseca, and Freeborn in southern Minnesota between 2014 and 2018., Patients and Methods: All possible and definite cases of IE (≥18 years) among residents of 6 counties in southern Minnesota, including Olmsted County, diagnosed between January 1, 2014, and December 31, 2018, were included in this retrospective, population-based investigation, using the Expanded Rochester Epidemiology Project (E-REP)., Results: Overall, 137 patients with IE developed incident IE in the 6-county region, corresponding to an age- and sex-adjusted incidence rate of 11.9 per 100,000 person-years. Men had a significantly higher incidence of IE (17.9 vs 6.8 per 100,000 person-years), and rates increased exponentially with age in both sexes. The median age of incident cases was 68.2 years, and 67.9% were male patients. The percentage of patients with histories of injection-drug use was low, at 6.7%. Bicuspid aortic valve was the most common (9.6%) native valve predisposing condition. Staphylococcus aureus was identified as the predominant pathogen in the overall group (34.8%), with viridans-group streptococci accounting for only 19.3% cases. Central nervous system and musculoskeletal complications were common. The 30-day readmission rate was 27.9%, and the 6-month mortality rate was 31.8%., Conclusion: To our knowledge, this is the first time that the population-based E-REP has been used to determine an age- and sex-adjusted IE incidence. Older male patients predominated, and S aureus was the most common pathogen. Based on these findings, it is not surprising that IE complications were frequently seen., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence., Methods and Results: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007., Conclusions: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Background: Nocardial brain abscesses are rare, and published literature describing brain abscesses due to Nocardia species is limited to individual case reports or small series. We report one of the largest contemporary retrospective studies describing risk factors, diagnostic evaluation, management, and outcomes of nocardial brain abscess., Methods: Retrospective review of all adults with brain abscess due to culture-confirmed Nocardia species at our institution between January 1, 2009, and June 30, 2020., Results: Overall, 24 patients had nocardial brain abscesses during the study period. The median age at presentation was 64 years, and 62.5% were immunocompromised. Pulmonary and cutaneous infections were the most common primary sites of nocardial infection. All 24 patients had magnetic resonance imaging performed, and the frontal lobe was the most commonly involved. The most common organism isolated was Nocardia farcinica , followed by Nocardia wallacei and Nocardia cyriacigeorgica . Thirteen patients were managed with antimicrobial therapy alone, while 11 had both medical and surgical management. In all patients, dual therapy was recommended for the initial 6 weeks of treatment, and 22 patients received at least 1 oral agent as part of their final antibiotic regimen, predominantly trimethoprim-sulfamethoxazole and linezolid. Fourteen patients achieved complete clinical and radiographic resolution of infection., Conclusions: Nocardia is an important cause of brain abscess in the immunocompromised host. Early diagnostic and therapeutic aspiration may help health care providers confirm the diagnosis, choose an appropriate antimicrobial regimen, and achieve source control., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: A population-based study of infective endocarditis (IE) in Olmsted County, Minnesota, provides a unique opportunity to define temporal and seasonal variations in IE incidence over an extended time period., Methods: This was a population-based review of all adults (≥18 years) residing in Olmsted County, Minnesota, with definite or possible IE using the Rochester Epidemiology Project from January 1, 1970, through December 31, 2018. Poisson regression was used to characterize the trends in IE incidence; models were fitted with age, sex, calendar time, and season, allowing for nonlinearity and nonadditivity of their effects., Results: Overall, 269 cases of IE were identified over a 49-year study period. The median age of IE cases was 67.2 years, and 33.8% were female. The overall age- and sex-adjusted incidence of IE was 7.9 cases per 100 000 person-years (95% CI, 7.0-8.9), with corresponding rates of 2.4, 2.4, 0.9, and 0.7 per 100 000 person-years for Staphylococcus aureus , viridans group streptococci (VGS), Enterococcus species, and coagulase-negative staphylococci IE, respectively. Temporal trends varied by age, sex, and season, but on average IE incidence increased over time ( P  = .021). Enterococcal IE increased the most ( P  = .018), while S. aureus IE appeared to increase but mostly in the winter months ( P  = .018). Between 1996 and 2018, the incidence of VGS IE was relatively stable, with no statistically significant difference in the trends before and after the 2007 AHA IE prevention guidelines., Conclusions: Overall, IE incidence, and specifically enterococcal IE, increased over time, while S. aureus IE was seasonally dependent. There was no statistically significant difference in VGS IE incidence in the periods before and after publication of the 2007 AHA IE prevention guidelines., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The improved life expectancy observed in patients living with human immunodeficiency virus (HIV) infection has made age-related cardiovascular complications, including arrhythmias, a growing health concern., Hypothesis: We describe the temporal trends in frequency of various arrhythmias and assess impact of arrhythmias on hospitalized HIV patients using the Nationwide Inpatient Sample (NIS)., Methods: Data on HIV-related hospitalizations from 2005 to 2014 were obtained from the NIS database using International Classification of Diseases, 9th Revision (ICD-9) codes. Data was further subclassified into hospitalizations with associated arrhythmias and those without. Baseline demographics and comorbidities were determined. Outcomes including in-hospital mortality, cost of care, and length of stay were extracted. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for analysis. A multivariable analysis was performed to identify predictors of arrhythmias among hospitalized HIV patients., Results: Among 2 370 751 HIV-related hospitalizations identified, the overall frequency of any arrhythmia was 3.01%. Atrial fibrillation (AF) was the most frequent arrhythmia (2110 per 100 000). The overall frequency of arrhythmias increased over time by 108%, primarily due to a 132% increase in AF. Arrhythmias are more frequent among older males, lowest income quartile, and nonelective admissions. Patients with arrhythmias had a higher in-hospital mortality rate (9.6%). In-hospital mortality among patients with arrhythmias decreased over time by 43.8%. The cost of care and length of stay associated with arrhythmia-related hospitalizations were mostly unchanged., Conclusions: Arrhythmias are associated with significant morbidity and mortality in hospitalized HIV patients. AF is the most frequent arrhythmia in hospitalized HIV patients., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Ascertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources., Methods: We retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs., Results: A total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse., Conclusions: Patients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To model and compare effect of digital contact tracing versus shelter-in-place on severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2) spread., Methods: Using a classical epidemiologic framework and parameters estimated from literature published between February 1, 2020, and May 25, 2020, we modeled two non-pharmacologic interventions - shelter-in-place and digital contact tracing - to curb spread of SARS-CoV-2. For contact tracing, we assumed an advanced automated contact tracing (AACT) application that sends alerts to individuals advising self-isolation based on individual exposure profile. Model parameters included percentage population ordered to shelter-in-place, adoption rate of AACT, and percentage individuals who appropriately follow recommendations. Under influence of these variables, the number of individuals infected, exposed, and isolated were estimated., Results: Without any intervention, a high rate of infection (>10 million) with early peak is predicted. Shelter-in-place results in rapid decline in infection rate at the expense of impacting a large population segment. The AACT model achieves reduction in infected and exposed individuals similar to shelter-in-place without impacting a large number of individuals. For example, a 50% AACT adoption rate mimics a shelter-in-place order for 40% of the population and results in a greater than 90% decrease in peak number of infections. However, as compared to shelter-in-place, with AACT significantly fewer individuals would be isolated., Conclusion: Wide adoption of digital contact tracing can mitigate infection spread similar to universal shelter-in-place, but with considerably fewer individuals isolated., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Infective endocarditis (IE), initially described more than 350 years ago, involves infection of the endocardial surface of the heart. The clinical manifestations of IE can involve every organ system, and the cardiac manifestations can include valvular vegetation, abscess, periannular extension of infection, and myopericarditis. Echocardiography is crucial in the diagnosis of IE, but alternative imaging modalities are playing an increasing role in the diagnosis and management of IE. Multidisciplinary care is imperative to the management of IE, often requiring the expertise of cardiologists, cardiothoracic surgeons, infectious diseases specialists, radiologists, and neurologists. We performed a literature search of the PubMed database from January 1st, 2000, to September 30th, 2019, using the terms infective endocarditis, diagnosis, and management to find the most pertinent and highest-quality evidence. This review summarizes key aspects of IE, with a focus on emerging advances in diagnosis. We also highlight growing patient populations at risk for IE, including patients with intracardiac devices and congenital heart disease., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the influence of acetylsalicylic acid (ASA) use on risk and outcome of community-acquired Staphylococcus aureus bacteremia (CA-SAB)., Method: We used population-based medical databases to identify all patients diagnosed in northern Denmark with first-time CA-SAB and matched population controls from 2000-2011. Categories for ASA users included current users (new or long-term users), former users, and nonusers. The analyses were adjusted for comorbidities, comedication use, and socioeconomic indicators., Results: We identified 2638 patients with first-time CA-SAB and 26 379 matched population controls. Compared with nonusers, the adjusted odds ratio (aOR) for CA-SAB was 1.00 (95% confidence interval [CI], 0.88-1.13) for current users, 1.00 (95% CI, 0.86-1.16) for former users, 2.04 (95% CI, 1.42-2.94) for new users, and 0.95 (95% CI, 0.84-1.09) for long-term users. Thirty-day cumulative mortality was 28.0% among current users compared with 21.6% among nonusers, yielding an adjusted hazard rate ratio (aHRR) of 1.02 (95% CI, 0.84-1.25). Compared with nonusers, the aHRR was 1.10 (95% CI, 0.87-1.40) for former users, 0.60 (95% CI, 0.29-1.21) for new users, and 1.06 (95% CI, 0.87-1.31) for long-term users. We observed no difference in the risk or outcome of CA-SAB with increasing ASA dose or by presence of diseases commonly treated with ASA., Conclusions: Use of ASA did not seem to influence the risk or outcome of CA-SAB. The apparent increased risk among new users may relate to residual confounding from the circumstances underlying ASA treatment initiation. Our finding of no association remained robust with increasing ASA dose and across multiple patient subsets., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To describe and compare the clinical presentation, management, and outcomes of cardiovascular implantable electronic device (CIED) infections due to gram-negative bacteria (GNB) and CIED infections due to gram-positive bacteria (GPB)., Patients and Methods: We retrospectively reviewed all CIED infection cases at Mayo Clinic from January 1, 1992, through December 31, 2015. Cases were classified based on positive microbiology data from extracted devices or blood cultures., Results: Of the 623 CIED infections during the study period, 31 (5.0%) were caused by GNB and 323 (51.8%) by GPB. Patients in the GNB group were more likely to present with local inflammatory findings at the pocket site (90.3% vs 72.4%; P=.03). All patients with bacteremia due to GNB had concomitant pocket infection compared with those with GPB (100% vs 33.9%; P=.002). After extraction, 41.9% of patients in the GNB group were managed with oral antibiotics vs 2.4% in the GPB group (P<.001). There were no statistically significant differences in infection relapse/recurrence or 1-year survival rates between the 2 groups., Conclusion: Compared with CIED infections caused by GPB, those due to GNB are more likely to present with pocket infection. Device-related GNB bacteremia almost always originates from the generator pocket. After extraction, oral antibiotic drug therapy may be a reasonable option in select cases of pocket infections due to GNB. No difference in outcomes was observed between the 2 groups., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Generator pocket infection is the most frequent presentation of cardiovascular implantable electronic device (CIED) infection. We aim to identify predictors of underlying bloodstream infection (BSI) in patients presenting with CIED pocket infection., Methods: We retrospectively reviewed all adults with CIED pocket infection cared for at our institution from January 2005 through January 2016. The CIED pocket infection cases were then subclassified as with or without associated BSI. Variables with P values <.05 at univariate analysis were included in a multivariable model to identify independent predictors of underlying BSI., Results: We screened 429 cases of CIED infection, and 95 met the inclusion criteria. Of these, 68 cases (71.6%) were categorized as non-BSI and 27 (28.4%) as BSI. There were no statistically significant differences in patient comorbid conditions or device characteristics between the 2 groups. In multivariable analysis, the presence of systemic inflammatory response syndrome criteria (tachycardia, tachypnea, fever or hypothermia, and leukocytosis or leukopenia) and hypotension were independent predictors of underlying BSI in patients presenting with CIED pocket infection. Overall, patients in the non-BSI group who did not receive pre-extraction antibiotics had a higher frequency of positive intraoperative pocket/device cultures than those with pre-extraction antibiotic exposure (79.4% vs 58.6%; P = .06)., Conclusions: Patients with CIED pocket infection who meet systemic inflammatory response syndrome criteria and/or are hypotensive at admission are more likely to have underlying BSI and should be started on empiric antibiotics after blood cultures are obtained. If these features are absent, it may be reasonable to withhold empiric antibiotics to optimize yield of pocket/device cultures during extraction.