Association Between Vegetation Size and Outcome in the Partial Oral Antibiotic Endocarditis Treatment Trial.

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.

Pulmonary arteriovenous malformations in patients with previous brain abscess: a cross-sectional population-based study.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. METHODS: This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). RESULTS: Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. CONCLUSIONS: Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

Implementation of early palliative care in an oncologic outpatient clinic - an observational study of the first year.

BACKGROUND: As earlier studies found that early onset specialized palliative care (ESPC) results in better quality of life (QoL), less hospitalization and chemotherapy toward end-of life, we implemented ESPC in our oncology outpatient clinic. The aim of this study was to describe reasons for referral, interventions performed and the satisfaction among the oncologic staff. MATERIAL AND METHODS: The outpatient ESPC clinic was established in the department of oncology. Prespecified selected data was obtained from the patients records. All patients were asked to fill in a questionnaire concerning their symptoms and QOL. A survey among the oncologic personnel concerning their perception of the clinic was conducted. All data were consecutively collected in a share point database. RESULTS: We included 134 patients. The primary referral symptoms were pain (69%) or psychological/existential challenges (23%). 55% of patients filled in an EORTC questionnaire and rated a median (QoL) of 3.4. Interventions initiated were on based on the following symptoms: pain (70%), constipation (53%), nausea (15%), dyspnea (10%) and depression (7%). Median waiting time was 13 days. Of the 134 patients referred to the ESPC clinic 101 was admitted. Symptoms and problems were resolved in the ESPC clinic for 81 of the 101 admitted patients (80%), i.e., after one consultation for 25 patients and after a follow up course in the clinic for 56 patients. A survey among the staff at the Department of Oncology demonstrated a high degree of satisfaction with the ESPC clinic. CONCLUSIONS: We report experiences from implementation of ESPC in our outpatient oncologic clinic, where 81 (80%) of the admitted patients could be finished after one or a few follow up contacts, as their symptoms had been resolved. There was a high degree of satisfaction with the clinic among the oncologic staff.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial.

PURPOSE: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. METHODS: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. RESULTS: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01). CONCLUSION: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. TRIAL REGISTRY: POET ClinicalTrials.gov number, NCT01375257.

Improved cardiovascular profile in Danish centenarians? A comparative study of two birth cohorts born 20 years apart.

PURPOSE: Cardiovascular health among middle-aged and older people has improved in high-income countries. It is unknown whether this also applies for the oldest-old and if so, is it driven by better treatment or by a health improvement? Therefore, we compared two Danish centenarian birth cohorts born in 1895 and 1915, respectively, to investigate if the cardiovascular profile had improved in the most recent born cohort. METHODS: All individuals turning 100 years old in 1995 and 2015, respectively, were included with participation rates of 74% (n = 106) and 79% (n = 238), respectively. Data were collected through structured in-home interviews. Cardiovascular profile was obtained by measured blood pressure, electrocardiogram (ECG), and information on medication. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. RESULTS: Mean SBP and DBP were almost identical in the two cohorts. Yet, the prevalence of measured hypertension was non-significantly higher in the 1895 cohort [73%, 95% CI (61;82)] compared to the 1915 cohort [63%, 95% CI (55;70)]. The proportion receiving at least one type of cardiovascular drug was significantly higher in the 1915 cohort [80%, 95% CI (74;86)] compared to 1895 cohort [66%, 95% CI 55;76)]. ECG findings were similar in the two cohorts, e.g., atrial fibrillation was present in 17% of the 1895 cohort and 20% of the 1915 cohort. CONCLUSION: This comparison study found a non-significant improvement in measured hypertension irrespective of medical treatment in the recent born cohort. Also, the recent born cohort was treated more intensively with cardiovascular drugs than earlier. However, the prevalence of pathological ECG-findings was unchanged.

Microbiological diagnosis in cardiac implantable electronic device infections detected by sonication and next-generation sequencing.

BACKGROUND: Device-related infection (DRI) is a severe complication of treatment with cardiac implantable electronic devices. Identification of the causative pathogen is essential for optimal treatment, but conventional methods often are inadequate. OBJECTIVE: The purpose of this study was to improve microbiological diagnosis in DRI using sonication and next-generation sequencing analysis. The primary objective was identification of causative pathogens. The secondary objective was estimation of the sensitivity of different microbiological methods in detecting the causative pathogen. METHODS: Consecutive patients with clinical signs of DRI between October 2016 and January 2019 from 3 tertiary centers in Denmark were included in the study. Patients underwent a diagnostic approach, including blood cultures and perioperative collection of microbiological samples (pocket swab, pocket tissue biopsies, generator, and leads). Conventional culturing was performed, and device components were sonicated and examined with an amplicon-based metagenomic analysis using next-generation sequencing. The results were compared with a reference standard-identified causative pathogen. RESULTS: In 110 patients with clinical signs of pocket (n = 50) or systemic DRI (n = 60), we collected 109 pocket swabs, 220 pocket tissue biopsies, 106 generators, 235 leads, and a minimum 1 set of blood cultures from 102 patients. Combining all findings, we identified the causative pathogen in 95% of cases, irrespective of DRI type. The usability of each microbiological method differed between DRI types. In pocket DRI, next-generation sequencing analysis of generators achieved sensitivity of 90%. For systemic DRI, blood cultures reached sensitivity of 93%. CONCLUSION: Using a strategy including sonication and next-generation sequencing, we identified the causative pathogen in 95% of DRI. Sensitivity of microbiological methods differed according to the type of DRI.

The impact of partial-oral endocarditis treatment on anxiety and depression in the POET trial.

BACKGROUND: The Partial-Oral versus Intravenous Antibiotic Treatment of Endocarditis Trial (POET) found that partial-oral outpatient treatment was non-inferior to conventional in-hospital intravenous treatment in patients with left-sided infective endocarditis. We examined the impact of treatment strategy on levels of anxiety and depression. METHODS: Patients completed the Hospital Anxiety and Depression Scale (HADS) at randomization, at antibiotic completion, and after month 3 and month 6. Changes in anxiety and depression (each subdimension 0-21, high scores indicating worse) were calculated using a repeated measure analysis of covariance model with primary assessment after 6 months. Change in score of 1.7 represented a minimal clinical important difference (MCID). RESULTS: Among the 400 patients enrolled in the POET trial, 263 (66%) completed HADS at randomization with reassessment rates of 86-87% at the three subsequent timepoints. Patients in the partial-oral group and the intravenous group had similar improvements after 6 months in levels of anxiety (-1.8 versus -1.6, P = 0.62) and depression (-2.1 versus -1.9, P = 0.63), although patients in the partial-oral group had numerically lower levels of anxiety and depression throughout. An improvement in MCID scores after 6 months was reported by 47% versus 45% (p = 0.80) patients for anxiety and by 51% versus 54% (p = 0.70) for depression. CONCLUSION: Patients with endocarditis receiving partial-oral outpatient treatment reported similar significant improvements in anxiety and depression at 6 months, as compared to conventionally treated, but numerically lower levels throughout. These findings support the usefulness of partial-oral treatment.

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis.

OBJECTIVE: To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality. METHODS: In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia. RESULTS: Out of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment. CONCLUSION: Moderate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Accelerated treatment of endocarditis-The POET II trial: Rationale and design of a randomized controlled trial.

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.

The epidemiology of infective endocarditis with focus on non-device related right-sided infective endocarditis: A retrospective register-based study in the region of Southern Denmark.

AIMS: Non-device related right-sided infective endocarditis (ND-RSIE) is not well characterized. We aimed to characterize patients with infective endocarditis (IE) with emphasis on the epidemiology, clinical characteristics and complications of ND-RSIE. METHODS: In this population-based cohort study, we identified patients with IE using ICD-10 codes from the Danish National Hospital Register in the Region of Southern Denmark between January 2007 and May 2017. Hospital records were reviewed, and characteristics and outcomes recorded. RESULTS: We included 1243 confirmed IE episodes of which 82% were left-sided IE, 11% were cardiac device right sided infective endocarditis (RSIE) and 7% were ND-RSIE. Patients with ND-RSIE were considerably younger, had less comorbidity and had a lower 30-day mortality (6%) compared with patients with device RSIE (24%) and left-sided IE (26%) (p<0.01). ND-RSIE was associated with underlying heart disease, involvement of the tricuspid valve (57%), Staphylococcus species (53%) and complications (61%). Forty percent of ND-RSIE occurred among people who inject drugs (PWID) for whom significant differences were observed compared with non-PWID with regards to tricuspid valve involvement (96% vs. 32%), causative microorganisms (Staphylococcus aureus 79% vs. 27%), complications (86% vs. 45%), recurrence (29% vs. 11%) and 30-day mortality (0% vs. 7%). CONCLUSION: ND-RSIE is relatively rare and differs with regards to epidemiology, clinical characteristics and complications compared with left-sided IE and cardiac device RSIE, but has a favourable prognosis. Forty percent of ND-RSIE occurs among PWID, which is associated with frequent complications but a very low mortality.

Prevalence of infective endocarditis in patients with positive blood cultures: a Danish nationwide study.

AIMS: Increasing attention has been given to the risk of infective endocarditis (IE) in patients with certain blood stream infections (BSIs). Previous studies have been conducted on selected patient cohorts, yet unselected data are sparse. We aimed to investigate the prevalence of IE in BSIs with bacteria typically associated with IE. METHODS AND RESULTS: By crosslinking nationwide registries from 2010 to 2017, we identified patients with BSIs typically associated with IE: Enterococcus faecalis (E. faecalis), Staphylococcus aureus (S. aureus), Streptococcus spp., and coagulase negative staphylococci (CoNS) and examined the concurrent IE prevalence. A trend test was used to examine temporal changes in the prevalence of IE. In total 69 021, distributed with 15 350, 16 726, 19 251, and 17 694 BSIs were identified in the periods of 2010-2011, 2012-2013, 2014-2015, and 2016-2017, respectively. Patients with E. faecalis had the highest prevalence of IE (16.7%) followed by S. aureus (10.1%), Streptococcus spp. (7.3%), and CoNS (1.6%). Throughout the study period, the prevalence of IE among patients with E. faecalis and Streptococcus spp. increased significantly (P = 0.0005 and P = 0.03, respectively). Male patients had a higher prevalence of IE for E. faecalis, Streptococcus spp., and CoNS compared with females. A significant increase in the prevalence of IE was seen for E. faecalis, Streptococcus spp., and CoNS with increasing age. CONCLUSION: For E. faecalis BSI, 1 in 6 had IE, for S. aureus BSI 1 in 10 had IE, and for Streptococcus spp. 1 in 14 had IE. Our results suggest that screening for IE seems reasonable in patients with E. faecalis BSI, S. aureus BSI, or Streptococcus spp. BSI.

Diagnosing heart failure in centenarians.

BACKGROUND: As a consequence of the demographic development with increasing proportion of older people, the prevalence of heart failure (HF) is expected to rise with considerable economic and societal costs. However, knowledge on cardiac structure and function among population-based samples of the exceptional old is lacking. METHODS: Population-based study of all persons (no exclusion criteria) living in the western part of Denmark and turning 100 years in the year 2015. In-home face-to-face interviews were conducted, and echocardiography and blood sampling for plasma Brain Natriuretic Peptide (BNP) were offered to those who were able to give consent. RESULTS: Out of 303 eligible, 238 (79%) participated, of which 125 (53%) accepted echocardiography. Left ventricular (LV) dysfunction was present in 68 (54%) of the participants of whom less than half had HF symptoms. Pulmonary hypertension was present in 31 (42%) with no correlation to LV function. The well-known association between increased level of BNP and the prevalence of LV dysfunction could not be confirmed. CONCLUSIONS: This in-home echocardiographic study shows that more than half of the participants had LV dysfunction, although mostly asymptomatic. There was no association between heart failure symptoms and LV dysfunction. Furthermore, BNP seems to have lost its biomarker potential to rule out heart failure in centenarians. Due to the latter, and the questionable symptom validity among centenarians, the current criteria to diagnose HF might be less valid in a centenarian population than in younger olds.

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis.

BACKGROUND: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).

Left ventricular mural thrombus despite treatment with dabigatran and clopidogrel.

We describe a case with severe heart failure and moderate aortic stenosis. Due to previous atrial fibrillation and ischaemic heart disease, this patient was treated with both dabigatran and clopidogrel. Despite this, a large mural thrombus was found on echocardiography. The treatment was altered to warfarin, but the thrombus did not resolve during the next eight months.Guidelines for the use of anticoagulant treatment in left ventricular thrombus are needed. Previously, a few cases presenting resistance to novel oral anticoagulants have been published and cases with thrombus formation due to dabigatran have been described. Our patient showed resistance to both dabigatran and warfarin, and there was no thrombus resolution when changing the treatment to warfarin.

Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis.

Most Staphylococcus aureus isolates can cause invasive disease given the right circumstances, but it is unknown if some isolates are more likely to cause severe infections than others. S. aureus bloodstream isolates from 120 patients with definite infective endocarditis and 121 with S. aureus bacteraemia without infective endocarditis underwent whole-genome sequencing. Genome-wide association analysis was performed using a variety of bioinformatics approaches including SNP analysis, accessory genome analysis and k-mer based analysis. Core and accessory genome analyses found no association with either of the two clinical groups. In this study, the genome sequences of S. aureus bloodstream isolates did not discriminate between bacteraemia and infective endocarditis. Based on our study and the current literature, it is not convincing that a specific S. aureus genotype is clearly associated to infective endocarditis in patients with S. aureus bacteraemia.

Virulence Factors Associated with Enterococcus Faecalis Infective Endocarditis: A Mini Review.

INTRODUCTION: The enterococci are accountable for up to 20% of all cases of infective endocarditis, with Enterococcus faecalis being the primary causative isolate. Infective endocarditis is a life-threatening infection of the endocardium that results in the formation of vegetations. Based on a literature review, this paper provides an overview of the virulence factors associated with E. faecalis infective endocarditis. Furthermore, it reports the effects of active or passive immunization against some of these involved factors. INDIVIDUAL VIRULENCE FACTORS: Nine virulence factors have in particular been associated with E. faecalis infective endocarditis. Absence of these factors entailed attenuation of strains in both mixed- and mono-bacterial infection endocarditis models as well as in in vitro and ex vivo assays when compared to their virulence factor expressing parental strains. PATHOGENESIS: The virulence factors promote a broad spectrum of events that together allow for disease development and progression. The infection is initiated through bacterial binding to ligands present at the site of infection after which the colonization can be accelerated through inter-bacterial attachment and modulation of the host immune response. The formation and growth of the vegetation provide protection and promote growth. Controlled degeneration of the vegetation appears to increase the likelihood of embolization and dissemination, without exposing protected bacteria. PROPHYLACTIC IMMUNIZATION: In most cases, active and passive immunization against associated virulence factors provided partial protection. FUTURE PROSPECTS: There is a need for further evaluation of the known virulence factors. Immunization against two or more virulence factors might be an effective prophylactic tool.