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Purpose: Patients with non-beta-hemolytic streptococcal bacteremia (NBHSB) are at risk of infective endocarditis (IE). Patients with cardiac implantable electronic device (CIED) have been described to have an increased risk of IE. The aim of the study was to describe a population-based cohort of patients with NBHSB and CIED and variables associated with IE and recurrent NBHSB., Methods: All episodes with NBHSB in blood culture from 2015 to 2018 in a population of 1.3 million inhabitants were collected from the Clinical Microbiology Laboratory, Lund, Sweden. Through medical records, patients with CIED during NBHSB were identified and clinical data were collected. Patients were followed 365 days after NBHSB., Results: Eighty-five episodes in 79 patients with CIED and NBHSB constituted the cohort. Eight patients (10%) were diagnosed with definite IE during the first episode, five of whom also had heart valve prosthesis (HVP). In 39 patients (49%) transesophageal echocardiography (TEE) was performed of which six indicated IE. Four patients had the CIED extracted. Twenty-four patients did not survive (30%) the study period. Four patients had a recurrent infection with NBHSB with the same species, three of whom had HVP and had been evaluated with TEE with a negative result during the first episode and diagnosed with IE during the recurrency., Conclusion: The study did not find a high risk of IE in patients with NBHSB and CIED. Most cases of IE were in conjunction with a simultaneous HVP. A management algorithm is suggested., (© 2024. The Author(s).)

Background: The 2023 Duke-International Society of Cardiovascular Infectious Diseases (ISCVID) criteria for infective endocarditis (IE) were introduced to improve classification of IE for research and clinical purposes. External validation studies are required., Methods: We studied consecutive patients with suspected IE referred to the IE team of Amsterdam University Medical Center (from October 2016 to March 2021). An international expert panel independently reviewed case summaries and assigned a final diagnosis of "IE" or "not IE," which served as the reference standard, to which the "definite" Duke-ISCVID classifications were compared. We also evaluated accuracy when excluding cardiac surgical and pathologic data ("clinical" criteria). Finally, we compared the 2023 Duke-ISCVID with the 2000 modified Duke criteria and the 2015 and 2023 European Society of Cardiology (ESC) criteria., Results: A total of 595 consecutive patients with suspected IE were included: 399 (67%) were adjudicated as having IE; 111 (19%) had prosthetic valve IE, and 48 (8%) had a cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than either the modified Duke or 2015 ESC criteria (84.2% vs 74.9% and 80%, respectively; P < .001) without significant loss of specificity. The 2023 Duke-ISCVID criteria were similarly sensitive but more specific than the 2023 ESC criteria (94% vs 82%; P < .001). The same pattern was seen for the clinical criteria (excluding surgical/pathologic results). New modifications in the 2023 Duke-ISCVID criteria related to "major microbiological" and "imaging" criteria had the most impact., Conclusions: The 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients with suspected IE., Competing Interests: Potential conflicts of interest. L. M. B. reports consulting fees from Boston Scientific and Roivant Sciences; UpToDate royalty payments, paid to the author (authorship duties); and consultant duties, paid to the author, from Botanix Pharmaceuticals. A. S. B. reports research grants from the National Institute of Allergy and Infectious Diseases, Akagera Medicines, ContraFect, and Riovant Pharmaceuticals and payment for expert testimony from Harrison, Skemp & Sleik and Patrick J. Higgins, Law. E. D. M. reports research funding for his institution from MSD, Pfizer, Angelini, Infectopharm, and Advanz Pharma; grants or contracts from Menarini and Shionogi; and personal fees, fees for participation on advisory boards, or speaker honoraria from Roche, Genentech, Pfizer, MSD, Angelini, Advanz Pharma, Bio-Merieux, Shionogi, Menarini, AbbVie, Sanofi-Aventis, Medtronic, Trx, and DiaSorin; and a role as secretary of the International Society for Cardiovascular Infectious Diseases. T. L. H. reports grants or contracts from Karius (adjudication committee) and the National Institutes of Health; royalties or licenses from UpToDate; consulting fees from Aridis, Pfizer, Lysovant, and Affinivax; and participation on a data and safety monitoring board for a platform trial for the SNAP Trial and on an advisory board for Basilea. A. W. K. reports a research grant from Karius (investigator-initiated grant to study plasma cell-free pathogen DNA in patients with endocarditis or infected cardiac implantable electronic device (CIEDs) having the intravascular site of infection removed); honoraria from Pfizer for service on a data and safety monitoring board; personal fees for consulting from Debio Pharma; royalties from UpToDate for chapters on infected CIEDs and prosthetic valve endocarditis; ownership of stock options in Pfizer, AbbVie, and Johnson & Johnson; and payment or honoraria for a chapter on infective endocarditis from McGraw-Hill education. J. M. M. reports consulting honoraria and/or research grants from Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Lysovant, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside the submitted work. P. M. reports support for meeting fees and travel as a member of the organizing committee (no direct payment) for the 16th International Society for Cardiovascular Infectious Diseases Symposium in Barcelona, Spain, 18–22 June 2022. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, 374 Achaogen, Affinium, The Medicines Company, MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer, grants from the National Institutes of Health, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the Infectious Diseases Society of America for service as the associate editor of Clinical Infectious Diseases; a sepsis diagnostics patent pending; and support from Contrafect for presenting phase 2 data at the 2019 European Congress of Clinical Microbiology and Infectious Diseases. 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.)

Background: Revised diagnostic criteria for infective endocarditis (IE), the 2023 Duke-ISCVID criteria, were recently presented and need validation. Here, we compare the 2000 modified Duke criteria for IE with Duke-ISCVID among patients with bacteremia and relate the diagnostic classification to IE treatment., Methods: We reanalyzed patient cohorts with Staphylococcus aureus, Staphylococcus lugdunensis, non-β-hemolytic streptococci, Streptococcus-like bacteria, Streptococcus dysgalactiae, Enterococcus faecalis, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) bacteremia. Episodes were classified as definite, possible, or rejected IE with the modified Duke and Duke-ISCVID criteria. Reclassification included the microbiology criteria, positron emission tomography-computed tomography, and cardiac implanted electronic devices. To calculate sensitivity, patients treated for IE were considered as having IE., Results: In 4050 episodes of bacteremia, the modified Duke criteria assigned 307 episodes (7.6%) as definite IE, 1190 (29%) as possible IE, and 2553 (63%) as rejected IE. Using the Duke-ISCVID criteria, 13 episodes (0.3%) were reclassified from possible to definite IE, and 475 episodes (12%) were reclassified from rejected to possible IE. With the modified Duke criteria, 79 episodes that were treated as IE were classified as possible IE, and 11 of these episodes were reclassified to definite IE with Duke-ISCVID. Applying the decision to treat for IE as a reference standard, the sensitivity of the Duke-ISCVID criteria was 80%. None of the 475 episodes reclassified to possible IE were treated as IE., Conclusions: The Duke-ISCVID criteria reclassified a small proportion of episodes to definite IE at the expense of more episodes of possible IE. Future criteria should minimize the possible IE group while keeping or improving sensitivity., Competing Interests: Potential conflicts of interest. The authors: no reported conflicts of interest. 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.)

Background: Patients with bacteraemia caused by gram-positive bacteria are at risk for infective endocarditis (IE). Because IE needs long antibiotic treatment and sometimes heart valve surgery, it is very important to identify patients with IE., Objectives: In this narrative review we present and discuss how to determine which investigations to detect IE that are needed in individual patients with gram-positive bacteraemia., Sources: Published original studies and previous reviews in English, within the relevant field are used., Content: First, the different qualities of the bacteraemia in relation to IE risk are discussed. The risk for IE in bacteraemia is related to the species of the bacterium but also to monomicrobial bacteraemia and the number of positive cultures. Second, patient-related factors for IE risk in bacteraemia are presented. Next, the risk stratification systems to determine the risk for IE in gram-positive bacteraemia caused by Staphylococcus aureus, viridans streptococci, and Enterococcus faecalis are presented and their use is discussed. In the last part of the review, an account for the different modalities of IE-investigations is given. The main focus is on echocardiography, which is the cornerstone of IE-investigations. Furthermore, 18 F-fluorodesoxyglucose positron emission tomography/computed tomography and cardiac computed tomography are presented and their use is also discussed. A brief account for investigations used to identify embolic phenomena in IE is also given. Finally, we present a flowchart suggesting which investigations to perform in relation to IE in patients with gram-positive bacteraemia., Implications: For the individual patient as well as the healthcare system, it is important both to diagnose IE and to decide when to stop looking for IE. This review might be helpful in finding that balance., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cardiac surgery is required in up to half of the patients with infective endocarditis (IE). Positive valve cultures have been associated with higher in-hospital mortality. The aims were to identify risk factors for positive valve cultures and its relation to outcome., Methods: Patients subjected to heart valve cultures due to surgery for IE in Skåne University Hospital, Lund, between 2012 and 2021 were identified through microbiology records. Risk factors for positive valve cultures and information on mortality and relapse were retrieved through medical records. Univariable and multivariable logistic regressions were performed., Results: A total of 345 episodes with IE in 337 patients subjected to cardiac surgery were included and valve cultures were positive in 78 (23%) episodes. In multivariable logistic regression, preoperative fever (adjusted odds ratio (AOR) 2.6, 95% confidence interval (CI) 1.2-5.6, p  = 0.02), prosthetic heart valve (AOR 3.3, CI 1.4-7.9, p  = 0.01), a single affected valve (AOR 4.8, CI 1.2-20, p  = 0.03), blood culture findings of S. aureus , enterococci, or coagulase negative staphylococci compared to viridans streptococci (AOR 20-48, p  < 0.001), and a shorter duration of antibiotic treatment ( p  < 0.001), were associated to positive valve culture. One-year mortality was 13% and a relapse was identified in 2.5% of episodes. No association between positive valve cultures and one-year mortality or relapse was identified., Conclusions: Positive valve cultures were associated to short preoperative antibiotic treatment, IE caused by staphylococci, preoperative fever and prosthetic valve but not to relapse or mortality.

Background/aim: Enterococcus faecalis and Enterococcus faecium cause human infections including bacteraemia and infective endocarditis (IE). Only few studies describing non-faecalis and non-faecium Enterococcus (NFE) infections have been conducted. We aimed to describe the incidence, prognosis, and focus of infection of bacteraemia with NFE., Methods: This retrospective population-based study included all episodes of patients having a blood culture with growth of NFE between 2012 and 2019 in Region Skåne, Sweden. Information was collected from medical records. Episodes of bacteraemia caused by NFE were compared to episodes of bacteraemia caused by E. faecalis and E. faecium., Results: During the study period, 136 episodes with NFE bacteraemia were identified corresponding to an incidence of NFE bacteraemia of 16 cases per 1,000,000 person-years among adults. Enterococcus casseliflavus (n=45), Enterococcus gallinarum (n=34), and Enterococcus avium (n=29) were the most common species. The most common foci of infection were biliary tract infections (n=17) followed by gastrointestinal infections (n=7). Urinary tract infections were not commonly caused by NFE (n=1), and no episodes of IE were caused by NFE. Polymicrobial bacteraemia was more common with NFE (73%) than with E. faecalis (35%) and E. faecium (42%). Community acquired infections were more common in bacteraemia with NFE compared to E. faecium. 30- and 90-day survival rates were 76% and 68%, respectively, and recurrent NFE bacteraemia was seen after 3% of the episodes., Conclusion: Bacteraemia caused by NFE is rare and is often polymicrobial. Biliary tract focus is common in NFE bacteraemia whereas IE and urinary tract focus are uncommon., (© 2023. The Author(s).)

Multiple episodes of Enterococcus faecalis bacteremia (EfsB) may indicate a relapse and be due to an undiagnosed infective endocarditis (IE). The aims were to study the clinical presentation of patients with EfsB with focus on the risk of recurrent infection and IE, identify potential improvements of the management, and to investigate whether E. faecalis isolates from different episodes in the same patient were identical. In a retrospective study, a cohort of patients with monomicrobial (M) EfsB episodes was analyzed. Clinical data from medical records were collected. Furthermore, blood culture isolates from patients with multiple episodes were subjected to whole genome sequencing and multilocus sequence typing. In 666 episodes of MEfsB, 69 patients with IE and 43 with recurrent infections were found. Patients without IE, but with a following episode diagnosed as IE, were compared to those without a following episode. Variables significantly correlated with IE were long duration of symptoms, growth in all blood cultures, unknown origin of infection, heart murmur, and predisposition for IE. Transesophageal echocardiography, all negative, was done in 4 out of 11 episodes during the first episodes, later diagnosed with IE. In 28 of 31 patients with two or more EfsB episodes, isolates with identical sequence type were found. Episodes of EfsB in patients later diagnosed with IE showed features of IE already during the first episodes, were not adequately evaluated, are due to identical isolates, and most likely represent true relapses. Risk factor analysis should guide the use of echocardiography., (© 2023. The Author(s).)

A substantial proportion of patients with infective endocarditis (IE) are subjected to heart valve surgery. Microbiological findings on valves are important both for diagnostics and for tailored antibiotic therapy, post-operatively. The aims of this study were to describe microbiological findings on surgically removed valves and to examine the diagnostic benefits of 16S-rDNA PCR and sequencing (16S-analysis). Adult patients who were subjected to heart valve surgery for IE between 2012 and 2021 at Skåne University Hospital, Lund, where a 16S-analysis had been performed on the valve, constituted the study population. Data were gathered from medical records, and the results from blood cultures, valve cultures, and 16S-analyses of valves were compared. A diagnostic benefit was defined as providing an agent in blood culture negative endocarditis, providing a new agent in episodes with positive blood cultures, or confirming one of the findings in episodes with a discrepancy between blood and valve cultures. 279 episodes in 272 patients were included in the final analysis. Blood cultures were positive in 259 episodes (94%), valve cultures in 60 episodes (22%), and 16S-analyses in 227 episodes (81%). Concordance between the blood cultures and the 16S-analysis was found in 214 episodes (77%). The 16S-analyses provided a diagnostic benefit in 25 (9.0%) of the episodes. In blood culture negative endocarditis, the 16S-analyses had a diagnostic benefit in 15 (75%) of the episodes. A 16S-analysis should be routinely performed on surgically removed valves in blood culture negative endocarditis. In patients with positive blood cultures, 16S-analysis may also be considered, as a diagnostic benefit was provided in some patients. IMPORTANCE This work demonstrates that it can be of importance to perform both cultures and analysis using 16S-rDNA PCR and sequencing of valves excised from patients undergoing surgery for infective endocarditis. 16S-analysis may help both to establish a microbiological etiology in cases of blood culture negative endocarditis and to provide help in situations where there are discrepancies between valve and blood cultures. In addition, our results show a high degree of concordance between blood cultures and 16S-analyses, indicating that the latter has a high sensitivity and specificity for the etiological diagnosis of endocarditis in patients who were subjected to heart valve surgery., Competing Interests: The authors declare no conflict of interest.

Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having infective endocarditis (IE). The objectives were to describe a Swedish population-based cohort of patients with CIED and SAB, to identify risk factors, and to construct a predictive score for IE. Patients over 18 years old in the Stockholm Region identified to have SAB in the Karolinska Laboratory database from January 2015 through December 2019 were matched to the Swedish Pacemaker and Implantable Cardioverter-Defibrillator ICD Registry to identify the study cohort. Data were collected from study of medical records. A cohort of 274 patients with CIED and SAB was identified and in 38 episodes (14%) IE were diagnosed, 19 with changes on the CIED, and 35 with changes on the left side of the heart. The risk factors predisposition for IE, community acquisition, embolization, time to positivity of blood cultures, and growth in blood culture after start of therapy in blood cultures were independently associated to IE. A score to identify patients with IE was constructed, the CTEPP score, and the chosen cut-off generated a sensitivity of 97%, specificity of 25%, and a negative predictive value of 98%. The score was externally validated in a population-based cohort of patients with CIED and SAB from another Swedish region. We found that 14% of patients with CIED and SAB had definite IE diagnosed. The CTEPP-score can be used to predict the risk of IE and, when negative, the risk is negligible., (© 2023. The Author(s).)

Background: Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus ( Sg gallolyticus ) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies., Methods: A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003-2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus ( Sg pasteurianus ) , S. lutetiensis and S. infantarius subsp. infantarius ( Si infantarius ) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology., Results: In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%) , Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) ( p  < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection., Conclusion: The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius , and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis .

Background: Prosthetic valve endocarditis (PVE) is a feared complication after heart valve surgery. Studies on differences in bacteriology in various types of PVE are limited., Objectives: This study aimed to investigate the microbiology of PVE depending on the type of prosthetic valve and timing of diagnosis., Methods: A retrospective study based on the Swedish Registry on Infective Endocarditis focusing on PVE was conducted. The cohort was divided into mechanical and bioprosthetic valves; into endocarditis localization in the aortic, mitral, or tricuspid valve; and into early and late PVE. The microbiology in these groups was compared. Predictors of Staphylococcus aureus as the cause of PVE were examined by multivariable logistic regression., Results: A total of 780 episodes of PVE in 749 patients were compared regarding the distribution of causative microbiological agents. The most common agents included alpha-hemolytic streptococci (29%), S. aureus (22%), enterococci (14%), coagulase-negative staphylococci (CoNS) (12%), and Cutibacterium acnes (6%). S. aureus was more commonly found on mechanical valves compared to bioprosthetic ones (36% vs. 17%, p < 0.001) whereas alpha-hemolytic streptococci, enterococci, and CoNS were more common on bioprosthetic valves. There were no significant differences in the microbiology of PVE affecting mitral or aortic valves or in cases of early and late PVE. Predictors for S. aureus as the cause of PVE were end-stage renal disease, intravenous drug use, mechanical valve, and tricuspid localization of endocarditis., Conclusions: The type of prosthetic heart valve is associated with the causative pathogen. Patients with mechanical valves are more likely to have PVE caused by S. aureus., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: A feared cause of bacteraemia with Gram-positives is infective endocarditis. Risk stratification scores can aid clinicians in determining the risk of endocarditis. Six proposed scores for the use in bacteraemia; Staphylococcus aureus (PREDICT, VIRSTA, POSITIVE), non-β-haemolytic streptococci (HANDOC) and Enterococcus faecalis (NOVA, DENOVA) were validated for predictive ability and the utilization of echocardiography was investigated., Methods: Hospitalized adult patients with Gram-positive bacteraemia during 2017-2019 were evaluated retrospectively through medical records and the Swedish Death Registry. Baseline and score-specific data, definite endocarditis and echocardiographies performed were recorded. Sensitivity, specificity, negative and positive predictive values and echocardiography utilization were determined., Results: 480 patients with bacteraemia were included and definite endocarditis was diagnosed in 20 (7.5%), 10 (6.6%), and 2 (3.2%) patients with S. aureus , non-β-haemolytic streptococci and E. faecalis, respectively. The sensitivities of the scores were 80-100% and specificities 8-77%. Negative predictive values of the six scores were 98-100%. VIRSTA, HANDOC, NOVA and DENOVA identified all, the PREDICT5 score missed 1/20 and the POSITIVE score missed 4/20 cases of endocarditis. Transoesophageal echocardiography was performed in 141 patients (29%). Thus, the risk stratification scores suggested an increase of 3-63 (7-77%) investigations with echocardiography., Conclusions: All scores had negative-predictive values over 98%, therefore it can be concluded that PREDICT5, VIRSTA, POSITIVE, HANDOC and DENOVA are reasonable screening tools for endocarditis early on in Gram-positive bacteraemia. The use of risk stratification scores will lead to more echocardiographies.

Cutibacterium is a genus often considered a contaminant when present in blood cultures, but it can also cause severe infections, especially related to implanted foreign materials. We investigated the incidence and features of patients with true Cutibacterium infection. Patients with positive Cutibacterium blood cultures between the years 2015-2020 in southern Sweden were identified through microbiology records and medical records were studied retrospectively. Cutibacterium isolates were species determined using MALDI-TOF MS. Patients were classified as having true infection or contamination according to a definition considering both clinical and microbiological features and these groups were compared. A total of 313 episodes of positive Cutibacterium blood cultures were identified in 312 patients. Of these, 49 (16%, corresponding to an incidence of 6 cases per million inhabitants per year) were classified as true infections. The most common species was Cutibacterium acnes (87%), and the majority were elderly men with comorbidities. Patients with true Cutibacterium infection often had an unknown focus of infection (n = 21) or a focus in the respiratory tract (n = 18). We identified one episode of ventriculo-peritoneal shunt infection, three episodes of aortic stent-graft infection, and one episode of infective endocarditis. Two patients, where Cutibacterium was isolated at the site of infection, had only one positive blood culture. The finding of positive Cutibacterium blood cultures should not always be considered contamination. Definitions of true Cutibacterium bacteremia with a demand that more than one blood culture must be positive may miss true infections., (© 2022. The Author(s).)

Non-β-hemolytic streptococci (NBHS) cause infective endocarditis (IE) and a short blood culture time to positivity (TTP) is associated with risk of IE in bacteremia with other pathogens. In this retrospective population-based cohort study, we investigate if TTP is associated to IE or mortality. Of 263 episodes with NBHS bacteremia, 28 represented IE and the median TTP did not differ significantly between episodes with IE (15 h) and non-IE (15 h) (p=0.51). TTP was similar among those who survived and those who died within 30 days. However, TTP significantly differed when comparing the different streptococcal groups (p<0.001)., (© 2021. The Author(s).)

Background Infective endocarditis is associated with higher mortality in elderly patients, but the role of surgery in this group has not been fully evaluated. The aim of this study was to assess outcomes of left-sided infective endocarditis in elderly patients and to determine the influence of surgery on mortality in the elderly. Methods and Results A nationwide retrospective study was performed of 2186 patients with left-sided infective endocarditis recorded in the SRIE (Swedish Registry of Infective Endocarditis), divided into patients aged <65 years (n=864), 65 to 79 years (n=806), and ≥80 years (n=516). Survival analysis was performed using the Swedish National Population Registry, and propensity score matching was applied to assess the effect of surgery on survival among patients of all ages. The rate of surgery decreased with increasing age, from 46% in the <65 group to 6% in the ≥80 group. In-hospital mortality was 3 times higher in the ≥80 group compared with the <65 group (23% versus 7%) and almost twice that of the 65 to 79 group (12%). In propensity-matched groups, the mortality rate was significantly lower between the ages of 55 and 82 years in patients who underwent surgery compared with patients who did not undergo surgery. Surgery was also associated with better long-term survival in matched patients who were ≥75 years (hazard ratio, 0.36; 95% CI, 0.24-0.54 [ P <0.001]). Conclusions The proportion of elderly patients with infective endocarditis who underwent surgery was low compared with that of younger patients. Surgery was associated with lower mortality irrespective of age. In matched elderly patients, long-term mortality was higher in patients who did not undergo surgery, suggesting that surgery is underused in elderly patients.

Objectives: Patients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems., Methods: This retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores., Results: A total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7-10.6) hours compared to those without, at 13.3 (10.5-16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91-100) and specificity of 52% (95% CI, 47-57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76-99) and a specificity of 70% (95% CI, 66-74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA., Conclusions: TTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Infective endocarditis (IE) caused by bacteria within Haemophilus (excluding Haemophilus influenzae), Aggregatibacter, Cardiobacterium, Eikenella and Kingella (HACEK) is rare. This study aimed to describe clinical features of IE caused by HACEK genera in comparison with IE due to other pathogens. Cases of IE due to HACEK were identified through the Swedish Registry of Infective Endocarditis (SRIE). Clinical characteristics of IE cases caused by HACEK were compared with cases of IE due to other pathogens reported to the same registry. Ninety-six patients with IE caused by HACEK were identified, and this corresponds to 1.8% of all IE cases. Eighty-three cases were definite endocarditis, and the mortality rate was 2%. The median age was 63 years, which was lower compared to patients with IE caused by other pathogens (66, 70 and 73 years respectively, p ≤ 0.01). Patients with IE caused by Haemophilus were younger compared to patients with IE due to Aggregatibacter (47 vs 67 years, p ≤ 0.001). Patients with IE due to HACEK exhibited longer duration from onset of symptoms to hospitalization and had more prosthetic valve endocarditis compared to patients with IE due to Staphylococcus aureus (10 vs 2 days, p ≤ 0.001, and 35 vs 14%, p ≤ 0.001). This is, to date, the largest study on IE due to HACEK. Aggregatibacter was the most common cause of IE within the group. The condition has a subacute onset and often strikes in patients with prosthetic valves, and the mortality rate is relatively low., (© 2021. The Author(s).)

Time to blood culture positivity (TTP) is an indirect measure of bacterial concentration in blood. A short TTP has been linked to the presence of infective endocarditis (IE) and to poor prognosis in Staphylococcus aureus bacteremia. We analyze factors influencing TTP in bacteremia with Enterococcus faecalis. This retrospective observational study of medical records included adults diagnosed with monomicrobial E. faecalis bacteremia between 2015 and 2018 in the Skåne region (Sweden). For each episode, the shortest TTP was recorded. Median TTP was compared between patients grouped based on age, sex, comorbidity, site of acquisition, and focus of infection. Using a dichotomized TTP (shorter or longer than 12 h), a multivariable logistic regression for factors associated to TTP was performed. The association between TTP and IE or mortality was evaluated. Three hundred sixty-seven episodes with monomicrobial E. faecalis bacteremia with the corresponding TTP were identified. Median TTP for the entire cohort was 11.6 (IQR 9.9-14.1) h and a significantly shorter TTP was noted for episodes which represented IE (n = 55, 9.4 (IQR 6.4-10.6) h). Only IE remained associated with a short TTP (≤ 12 h) in binary logistic regression analysis. Factors associated with IE were investigated and TTP was associated with IE also when adjusted for age, gender, comorbidity, and nosocomial acquisition. There was no association between TTP and mortality. A low TTP is associated with IE in E. faecalis bacteremia and could be used as a help in determining the need for echocardiography in patients with this condition., (© 2021. The Author(s).)

We present characteristics of infective endocarditis (IE) caused by Staphylococcus lugdunensis and compare with IE caused by Staphylococcus aureus and other CoNS, in the National Swedish Registry of IE (2008-2018). Thirty episodes of S. lugdunensis IE were registered, of which 21 cases affected native valves, and 7 patients were subjected to surgery. The mortality rate at 30 days was significantly higher for S. lugdunensis IE (20%, n = 6), than for IE caused by other CoNS (7%) or S. aureus (9%) p = 0.016. Septic embolisation was only reported in two cases (7%). The most common treatment was isoxazolyl penicillin (n = 18).

The objective was to describe the epidemiology, bacteriology, clinical presentation, risk factors for endocarditis (IE), diagnostic workup, and outcome of patients with bacteremia caused by the non-influenzae Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella genera (HACEK). A retrospective population-based cohort of patients with bacteremia collected from 2012 to 2017 was identified. Clinical data from identified patients were collected from medical records to classify patients, calculate incidences, analyze risk factors of IE, and describe the management and outcome of the cohort. A total of 118 episodes of HACEK bacteremia were identified, of which 27 were definite IE. The incidence of HACEK bacteremia was 5.2 and of HACEK IE 1.2 episodes per 1,000,000 inhabitants per year. Other focal infections were identified in 55 of 118 of the episodes, most commonly within the abdomen (26 episodes). The propensity to cause IE ranged from 62 in Aggregatibacter actinomycetemcomitans to 6% in Eikenella. Risk factors for IE were cardiac implantable electronical device, predisposing cardiac conditions, community acquisition, long duration of symptoms, multiple positive blood cultures, fever, heart murmur, embolization, and unknown origin of infection. The scoring system DENOVA developed to predict IE in bacteremia with Enterococcus faecalis also had a high sensitivity and specificity for predicting IE in HACEK bacteremia. The 30-day mortality was 4% in IE and 15% in non-IE bacteremia, and only one case of relapse was found. IE is common in bacteremia with Aggregatibacter, Cardiobacterium, and Kingella but relatively rare in Haemophilus and Eikenella. Treatment failures are very rare, and DENOVA can be used to evaluate the need for transesophageal echocardiography.

The aim of the study was to compare background characteristics, microbiology and outcome of patients with right-sided and left-sided intravenous drug use (IDU) associated infective endocarditis (IE). A nationwide retrospective study using the Swedish Registry on Infective Endocarditis between 2008 and 2019 was conducted. A total of 586 people with IDU-IE were identified and divided into left-sided (n = 204) and right-sided (n = 382) IE. Descriptive statistics, Cox-regression and Kaplan-Meier survival estimates were used. The mean age of patients in the left-sided group was 46 years compared to 35 years in the right-sided group, p < 0.001. Left-sided IE had a higher proportion of females. Staphylococcus aureus was the causative pathogen in 48% of cases in the left-sided group compared to 88% in the right-sided group. Unadjusted and adjusted long-term survival was better in right-sided IE compared to left-sided IE. Independent predictors of long-term mortality were increasing age, end-stage renal disease, nosocomial infection, brain emboli and left-sided IE. Left-sided IE was common in people with IDU but the proportion of females with left-sided IE was low. S. aureus was twice as common in right-sided IE compared to left-sided IE, and the long-term prognosis of right sided IDU-associated IE was better compared to left-sided IE despite the fact that few were operated.

Background: The optimal antibiotic treatment length for infective endocarditis (IE) is uncertain. International guidelines recommend treatment duration of up to 6 weeks for patients with left-sided IE but are primarily based on historical data and expert opinion. Efficacies of modern therapies, fast recovery seen in many patients with IE, and complications to long hospital stays challenge the rationale for fixed treatment durations in all patients., Objective: The objective was to conduct a noninferiority randomized controlled trial (acronym POET II) investigating the safety of accelerated (shortened) antibiotic therapy as compared to standard duration in patients with left-sided IE., Methods: The POET II trial is a multicenter, multinational, open-label, noninferiority randomized controlled trial. Patients with definite left-sided IE due to Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis will be eligible for enrolment. Each patient will be randomized to accelerated antibiotic treatment or standard-length treatment (1:1) following clinical stabilization as defined by clinical parameters, laboratory values, and transesophageal echocardiography findings. Accelerated treatment will be between 2 and 4 weeks, whereas standard-length treatment will be between 4 and 6 weeks, depending on microbiologic etiology, complications, need for valve surgery, and prosthetic versus native valve endocarditis. The primary outcome is a composite of all-cause mortality, unplanned cardiac surgery, relapse of bacteremia, or embolization within 6 months of randomization., Conclusions: The POET II trial will investigate the safety of accelerated antibiotic therapy for patients with left-sided IE caused by Streptococcus spp, Staphylococcus aureus, or Enterococcus faecalis. The results of the POET II trial will improve the evidence base of treatment recommendations, and clinical practice may be altered., Competing Interests: Declaration of competing interest Robert Horvath has received sponsorship for symposia from MSD. The other authors have nothing to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Invasive infections with non-beta-haemolytic streptococci (NBHS) is quite common and presents the clinicians with difficulties regarding which patients are at risk for infective endocarditis (IE). The HANDOC score was developed to identify patients with NBHS bacteraemia who are at low risk of IE. This study was conducted to validate HANDOC in an external cohort. Methods: Patients with NBHS in blood cultures between March and September 2016 in a Danish centre were included as part of an on-going study. Patient characteristics were collected to classify bacteria according to Dukés criteria and the components of the HANDOC score were collected retrospectively from the patients' medical records. Results: 68 patients were included in the cohort, of which 16 fulfilled Dukés criteria for IE. All patients with IE (16 of 16) had a HANDOC score above the predefined cut-off. Cases of IE were found in patients with. Streptococcus mitis , Streptococcus bovis , Streptococcus mutans, Streptococcus anginosus , and Streptococcus sanguinis group streptococci. The HANDOC score thus had a sensitivity of 100% and a specificity of 62% in this cohort. Conclusions: HANDOC has a sensitivity of 100% and a relatively high specificity (62%) also in a prospectively enrolled cohort of patients from another country than its origin. This indicates that HANDOC can be implemented in clinical practice to identify patients with a low risk of IE in whom echocardiography can be omitted.

Corynebacterium is a genus that can contaminate blood cultures and also cause severe infections like infective endocarditis (IE). Our purpose was to investigate microbiological and clinical features associated with contamination and true infection. A retrospective population-based study of Corynebacterium bacteremia 2012-2017 in southern Sweden was performed. Corynebacterium isolates were species determined using a matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Patient were, from the medical records, classified as having true infection or contamination caused by Corynebacterium through a scheme considering both bacteriological and clinical features and the groups were compared. Three hundred thirty-nine episodes of bacteremia with Corynebacterium were identified in 335 patients of which 30 (8.8%) episodes were classified as true infection. Thirteen patients with true bacteremia had only one positive blood culture. Infections were typically community acquired and affected mostly older males with comorbidities. The focus of infection was most often unknown, and in-hospital mortality was around 10% in both the groups with true infection and contamination. Corynebacterium jeikeium and Corynebacterium striatum were significantly overrepresented in the group with true infection, whereas Corynebacterium afermentans was significantly more common in the contamination group. Eight episodes of IE were identified, all of which in patients with heart valve prosthesis. Six of the IE cases affected the aortic valve and six of seven patients were male. The species of Corynebacterium in blood cultures can help to determine if a finding represent true infection or contamination. The finding of a single blood culture with Corynebacterium does not exclude true infection such as IE.

Objectives: Enterococcal bacteremia can be complicated by infective endocarditis (IE) and when suspected, transesophageal echocardiography (TEE) should be performed. The previously published NOVA score can identify patients with enterococcal bacteremia at risk for IE and we aimed to improve the score., Methods: Factors associated with IE were studied retrospectively in a population-based cohort of patients with monomicrobial Enterococcus faecalis bacteremia (MEFsB). Factors associated with IE in multivariable analysis were included in a new score system which was compared to the NOVA score and validated in a cohort of patients with MEFsB from another region., Results: Among 397 episodes of MEFsB, 44 episodes with IE were compared to those without IE. Long Duration of symptoms (≥ 7 days) and Embolization were associated with IE in the multivariate analysis and hence were added to the NOVA variables (Number of positive cultures, Origin of infection unknown, Valve disease, and Auscultation of murmur) to generate a novel score; DENOVA. The area under the curve in ROC analyses was higher for DENOVA (0.95) compared to NOVA (0.91) (p = 0.001). With a cutoff at ≥ 3 positive variables the DENOVA score has a sensitivity of 100% and specificity of 83% which is superior to the NOVA score (specificity 29%). The DENOVA score was applied to the validation cohort (26 IE episodes and 256 non-IE episodes) and the resulting sensitivity was 100% and the specificity was 85% compared to 35% for NOVA., Conclusions: The DENOVA score is a useful tool to identify patients with MEFsB where TEE is not needed.

Knowledge of infective endocarditis (IE) caused by Streptococcus dysgalactiae (SD) is limited. This study aimed to identify the clinical and microbiological features of SD-caused IE and to investigate any possible synergy between penicillin and gentamicin on SD isolates. Cases of IE 2008-2016 due to SD reported to the Swedish Registry of Infective Endocarditis (SRIE) were identified. Isolates were emm typed and synergy between antibiotics was determined in time-kill experiments. Medical records were reviewed and SD-cases were compared to cases of IE due to other pathogens reported to the SRIE. Fifty cases of SD-caused IE were confirmed. emm types stC74a, stG62647, and stG643 were most commonly encountered. The patients had a median age of 74 years (range 38-93) and were significantly older compared to patients with Staphylococcus aureus-caused IE, (65 years (p = 0.003)). The median time to diagnosis from symptom onset was 1 day for patients with SD-caused IE which was less compared to patients with IE due to the other pathogens (2-15 days). Embolization was seen in 46% and the in-hospital mortality was 8%. Etest-based methods did not indicate any synergy between penicillin and gentamicin whereas synergy was noted for four out of nine isolates applying time-kill assays. This is the largest study of SD-caused IE, a condition with an acute onset predominantly affecting elderly people. Synergy between penicillin and gentamicin against some SD isolates was distinguished but the potential benefit of this must be weighed against the risk of aminoglycoside side effects.

Background: Non-β-hemolytic streptococci (NBHS) can cause infective endocarditis (IE). Echocardiography is used to diagnose IE, but it is not known which patients with NBHS bacteremia should undergo echocardiography., Method: Medical records of patients with NBHS bacteremia in southern Sweden from 2012 to 2014 were studied retrospectively. The patients were divided into 2 cohorts. In the first, correlations between the reported data and IE were studied. These variables were used to construct the HANDOC score, which was then validated in the second cohort., Results: Three hundred thirty-nine patients with NBHS bacteremia were included in the first cohort, of whom 26 fulfilled the criteria for IE. Several factors differed significantly between the patients with IE and those without. Among these variables, the presence of Heart murmur or valve disease; Aetiology with the groups of Streptococcus mutans, Streptococcus bovis, Streptococcus sanguinis, or Streptococcus anginosus; Number of positive blood cultures ≥2; Duration of symptoms of 7 days or more; Only 1 species growing in blood cultures; and Community-acquired infection were chosen to form the HANDOC score. With a cutoff between 2 and 3 points, HANDOC had a sensitivity of 100% and specificity of 73% in the first cohort. When tested in the validation cohort (n = 399), the sensitivity was 100% and the specificity 76%., Conclusions: HANDOC can be used in to identify patients with NBHS bacteremia who have a risk of IE so low that echocardiography can be omitted; therefore, its implementation might reduce the use of echocardiography., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Streptococci are common causes of infective endocarditis (IE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has provided a practical tool for their species determination. We aimed to investigate if particular groups of non-beta heamolytic streptococci were associated with IE or to specific presentations thereof. The Swedish Registry of Infective Endocarditis was used to identify cases of IE caused by streptococci and a local database to identify cases of streptococcal bacteremia. The bacteria were grouped using MALDI-TOF MS and the clinical characteristics of IE caused by different groups were compared. We identified a group of 201 streptococcal IE isolates: 18 isolates belonged to the anginosus, 19 to the bovis, 140 to the mitis, 17 to the mutans, and seven to the salivarius groups. The mitis and mutans groups were significantly more common and the anginosus group less common among IE cases as compared to all cause bacteremia. Patients infected with the bovis group isolates were older, had more cardiac devices, and had more commonly prosthetic valve IE compared to IE caused by streptococci of the other groups. Twenty-one percent of patients needed surgery, and in-hospital mortality was 8% with no significant differences between the groups. Grouping of non-beta haemolytic streptococci using MALDI-TOF MS can provide a basis for decision-making in streptococcal bacteremia. IE caused by bovis group isolates have clinical characteristics distinguishing them from IE caused by other groups of Streptococcus.

Streptococcus spp. are important causes of infective endocarditis but challenging in species identification. This study compared identification based on sequence determination of the rnpB gene with 2 systems of matrix-assisted laser desorption ionization-time of flight mass spectrometry, MALDI Biotyper (Bruker) and VITEK MS IVD (bioMérieux). Blood culture isolates of viridans streptococci from 63 patients with infective endocarditis were tested. The 3 methods showed full agreement for all 36 isolates identified in the Anginosus, Bovis, and Mutans groups or identified as Streptococcus cristatus, Streptococcus gordonii, or Streptococcus sanguinis. None of the methods could reliably identify the 23 isolates to the species level when designated as Streptococcus mitis, Streptococcus oralis, or Streptococcus tigurinus. In 7 isolates classified to the Mitis group, the rnpB sequences deviated strikingly from all reference sequences, and additional analysis of sodA and groEL genes indicated the occurrence of yet unidentified Streptococcus spp., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Lactococcus garvieae is a rare cause of infective endocarditis (IE) in humans and the bacterium can easily be misidentified. Intracranial haemorrhage often occurs in conjunction with IE, but subdural haemorrhage (SDH) is very rarely encountered., Case Presentation: The patient was an 81-year-old male with a history of cardiovascular disease and a prosthetic biologic aortic valve. He presented with fatigue and an acute onset of headache. Computed tomography (CT) revealed a left-sided fronto-temporal subdural haematoma. Low-grade fever was noted and blood cultures yielded growth of L. garvieae. Transesophageal echocardiography (TEE) revealed small vegetations on the native mitral valve and on the prosthetic aortic valve. Treatment with penicillin and tobramycin was initiated and the recovery was slow but uneventful., Conclusion: This is the first report of a case where SDH was the sole presenting neurological sign of IE. The case demonstrates that IE should be considered in patients with SDH where a history of trauma is absent, especially if the patient has fever or predisposing conditions such as a prosthetic heart valve.

Infective endocarditis (IE) is a severe infection associated with significant morbidity and mortality. Enterococcus faecalis is among the most common causes of this disease, and yet little is known about the pathogenesis of E. faecalis IE. We screened 21 E. faecalis isolates from IE and 21 isolates from normal flora for the putative virulence factors ace, asa1, gelE, and esp with PCR. In addition, we determined the ability of the isolates to form biofilm and to aggregate platelets. With the exception of biofilm formation, which was more pronounced in the normal flora group, there was no difference between the groups, indicating that many isolates have virulence properties and that host factors might determine if E. faecalis causes IE., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The Gram-positive bacterium Aerococcus urinae can cause infectious endocarditis (IE) in older persons. Biofilm formation and platelet aggregation are believed to contribute to bacterial virulence in IE. Five A. urinae isolates from human blood were shown to form biofilms in vitro, and biofilm formation was enhanced by the presence of human plasma. Four of the A. urinae isolates caused platelet aggregation in platelet-rich plasma from healthy donors. The Au3 isolate, which induced platelet aggregation in all donors, also activated platelets, as determined by flow cytometry. Platelet aggregation was dependent on bacterial protein structures and on platelet activation since it was sensitive to both trypsin and prostaglandin E(1). Plasma proteins at the bacterial surface were needed for platelet aggregation; and roles of the complement system, fibrinogen, and immunoglobulin G were demonstrated. Complement-depleted serum was unable to support platelet aggregation by Au3 and complement blockade using compstatin-inhibited platelet activation. Platelet activation by Au3 was inhibited by blocking of the platelet fibrinogen receptor, and this isolate was also shown to bind to radiolabeled fibrinogen. Removal of IgG from platelet-rich plasma by a specific protease inhibited the platelet aggregation induced by A. urinae, and blockade of the platelet FcRγIIa hindered platelet activation induced by Au3. Convalescent-phase serum from a patient with A. urinae IE transferred the ability of the bacterium to aggregate platelets in an otherwise nonresponsive donor. Our results show that A. urinae exhibits virulence strategies of importance for IE.