Non-betahemolytic streptococcal bacteremia, cardiac implantable electronic device, endocarditis, extraction, and outcome; a population-based retrospective cohort study.

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.

Make modern microbiology matter more in the 2023 ESC guidelines for the management of infective endocarditis.

The ESC 2023 guidelines for the management of endocarditis stress that a multidisciplinary approach is needed to manage patients with infective endocarditis (IE). In our view the guidelines do not include the relevant perspectives from modern microbiology. The diagnostic criteria for IE were changed in the ESC 2023 guidelines and many IE-causing pathogens are either not clearly defined or not even mentioned. Moreover, the improved understanding of the relation between bacterial species and the risk for IE has not been implemented. The guidelines give detailed, and in our view not correct, instructions about diagnostic testing in blood culture negative IE without presenting proper evidence. Other important diagnostic aspects such as the value of repeated blood cultures and incubation time for blood cultures are not discussed. We believe that a multidisciplinary collaboration, including microbiologists, would have improved these guidelines and we hope for a future harmonization of diagnostic criteria for IE.

Lower specificity of the ESC2023 diagnostic criteria for infective endocarditis when spondylodiscitis is regarded as a vascular phenomenon.

The ESC diagnostic criteria for infective endocarditis (IE) added spondylodiscitis as minor diagnostic criterion. Of patients with Staphylococcus aureus, streptococcal or Enterococcus faecalis bacteremia, 11 of 1807 episodes were reclassified to definite IE of which nine were not treated as IE. Spondylodiscitis as a minor criterion decreases specificity of the criteria.

Disentangling hydroxynitrile glucoside biosynthesis in a barley (Hordeum vulgare) metabolon provides access to elite malting barleys for ethyl carbamate-free whisky production.

Barley produces several specialized metabolites, including five α-, ß-, and γ-hydroxynitrile glucosides (HNGs). In malting barley, presence of the α-HNG epiheterodendrin gives rise to undesired formation of ethyl carbamate in the beverage production, especially after distilling. Metabolite-GWAS identified QTLs and underlying gene candidates possibly involved in the control of the relative and absolute content of HNGs, including an undescribed MATE transporter. By screening 325 genetically diverse barley accessions, we discovered three H. vulgare ssp. spontaneum (wild barley) lines with drastic changes in the relative ratios of the five HNGs. Knock-out (KO)-lines, isolated from the barley FIND-IT resource and each lacking one of the functional HNG biosynthetic genes (CYP79A12, CYP71C103, CYP71C113, CYP71U5, UGT85F22 and UGT85F23) showed unprecedented changes in HNG ratios enabling assignment of specific and mutually dependent catalytic functions to the biosynthetic enzymes involved. The highly similar relative ratios between the five HNGs found across wild and domesticated barley accessions indicate assembly of the HNG biosynthetic enzymes in a metabolon, the functional output of which was reconfigured in the absence of a single protein component. The absence or altered ratios of the five HNGs in the KO-lines did not change susceptibility to the fungal phytopathogen Pyrenophora teres causing net blotch. The study provides a deeper understanding of the organization of HNG biosynthesis in barley and identifies a novel, single gene HNG-0 line in an elite spring barley background for direct use in breeding of malting barley, eliminating HNGs as a source of ethyl carbamate formation in whisky production.

Staphylococcus aureus bacteraemia, cardiac implantable electronic device, extraction, and the risk of recurrent infection; a retrospective population-based cohort study.

BACKGROUND: Patients with cardiac implantable electronic device (CIED) and Staphylococcus aureus bacteraemia (SAB) are at risk of having CIED infection, pocket infection or endocarditis. To avoid treatment failures, guidelines recommend that the CIED should be extracted in all cases of SAB butrecent studies indicate low extraction rates and low risk of relapse. The aim of the study was to describe a Swedish population-based cohort of patients with CIED and SAB, the rate of extraction, and treatment failure measured as recurrent SAB. METHODS: Patients identified to have SAB in the Karolinska Laboratory database, serving a population of 1.9 million, from January 2015 through December 2019 were matched to the Swedish ICD and Pacemaker Registry. Patients with CIED and SAB were included. Clinical data were collected from medical records. RESULTS: A cohort of 274 patients was identified and 38 patients (14%)had the CIED extracted. Factors associated with extraction were lower age, lower Charlson comorbidity index, shorter time since CIED implantation, and non-nosocomial acquisition, but not mortality. No patient was put on lifelong antibiotic treatment. Sixteen patients (6%) had a recurrent SAB within one year, two in patients subjected to extraction (5%) and 14 in patients not subjected to CIED-extraction (6%). Three of the 14 patients were found to have definite endocarditis during the recurrent episode. CONCLUSIONS: Despite a low extraction rate, there were few recurrences. We suggest that extraction of the CIED might be omitted if pocket infection, changes on the CIED, or definite endocarditis are not detected.

Performance of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis in Relation to the Modified Duke Criteria and to Clinical Management-Reanalysis of Retrospective Bacteremia Cohorts.

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-ß-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.

External Validation of the 2023 Duke-International Society for Cardiovascular Infectious Diseases Diagnostic Criteria for Infective Endocarditis.

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.

Bacteraemia with gram-positive bacteria-when and how do I need to look for endocarditis?

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, 18F-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.

Bacteraemia caused by non-faecalis and non-faecium Enterococcus species-a retrospective study of incidence, focus of infection, and prognosis.

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.

Risk factors for and consequences of positive valve cultures in patients who undergo cardiac surgery while receiving antimicrobial treatment for infective endocarditis.

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.

Recurrent bacteremia with Enterococcus faecalis, the clinical findings predicting endocarditis, and genomic characterization of the isolates: a retrospective cohort study.

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.

Clinical Significance of a 16S-rDNA Analysis of Heart Valves in Patients with Infective Endocarditis: a Retrospective Study.

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.

Treatment refractory arthritis and stroke - A case of infective endocarditis caused by Tropheryma whipplei.

Whipple´s disease is a rare multisystem condition affecting < 1/1.000.000 per year. The condition often presents with polyarthritis, diarrhea, and intestinal malabsorption. Endocarditis is seen in a minority of these patients, and is typically culture negative, as the causative agent Tropheryma whipplei does not grow in ordinary culture media. We present the case of a 78-year-old man with a history of seronegative polyarthritis that was refractory to treatment with several biological agents for a duration of 5 years prior to presentation to the emergency department with stroke. Echocardiography revealed aortic valve endocarditis with a 3.6 cm vegetation and multiple smaller vegetations. The patient underwent surgery with aortic valve replacement followed by prolonged antibiotic treatment. 16 S rDNA PCR analysis of the resected valve revealed T. whipplei as the causative agent. Two years after surgery and treatment with antibiotics, the patient's previously longstanding arthritis had totally disappeared and all rheumatological treatment had been discontinued.

Fatal infective endocarditis caused by Aerococcus sanguinicola: a case report and literature review.

Aerococcus sanguinicola is a bacterium that can cause urinary tract infections and on rare occasions infective endocarditis (IE). The prognosis of IE caused by aerococci is generally favourable despite that the patients are typically old and have multiple comorbidities. Here we report a case of A. sanguinicola native valve aortic IE in a 68-year-old man with an underlying urinary tract condition. The infection led to severe aortic valve insufficiency and rapid death before the patient could be subjected to surgery. This demonstrates that IE caused by A. sanguinicola can be severe and cause valve destruction. In addition to the case report, we provide a review of the current literature on A. sanguinicola IE.

Staphylococcus aureus bacteraemia, cardiac implantable electronic device, and the risk of endocarditis: a retrospective population-based cohort study.

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.

Time to positivity of blood cultures in bloodstream infections with Streptococcus dysgalactiae and association with outcome.

PURPOSE: Invasive infections with Streptococcus dysgalactiae predominantly occur in persons of older age with substantial morbidity and mortality. Time to positivity from blood cultures (TTP) has been shown to be a prognostic indicator in bloodstream infections caused by other beta-haemolytic streptococci. This study aimed to determine any possible association between TTP and outcome in invasive infections due to S. dysgalactiae. MATERIALS AND METHODS: Episodes of S. dysgalactiae bacteraemia, that occurred during 2015-2018 in the Region of Skåne, Sweden, were identified through the laboratory database and retrospectively studied. Any association with TTP and the primary outcome, death within 30 days and the development of sepsis or disease deterioration within 48 hours from blood culturing as secondary outcomes were investigated. RESULTS: Among the 287 episodes of S. dysgalactiae bacteraemia, 30-day mortality rate was 10% (n = 30). Median TTP was 9.3 h (interquartile range 8.0-10.3 h). Median TTP was statistically significantly shorter in patients who died within 30 days compared to surviving patients (7.7 vs 9.3 h, p = .001, Mann-Whitney U test). Short TTP(≤ 7.9 h) was still associated with 30-day mortality when adjusting for age, (OR 4.4, 95% CI 1.6-12.2, p = .004). Associations between secondary outcomes and levels of TTP were not observed. CONCLUSION: TTP may be an important prognostic indicator for 30-day mortality in patients with bloodstream infections due to S. dysgalactiae.