Rasmus V. Rasmussen

Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography

AIMS Staphylococcus aureus infective endocarditis (IE) is a critical medical condition associated with a high morbidity and mortality. In the present study, we prospectively evaluated the importance of screening with echocardiography in an unselected S. aureus bacteraemia (SAB) population. METHODS AND RESULTS From 1 January 2009 to 31 August 2010, a total of 244 patients with SAB at six Danish hospitals underwent screening echocardiography. The inclusion rate was 73% of all eligible patients (n= 336), and 53 of the 244 included patients (22%; 95% CI: 17-27%) were diagnosed with definite IE. In patients with native heart valves the prevalence was 19% (95% CI: 14-25%) compared with 38% (95% CI: 20-55%) in patients with prosthetic heart valves and/or cardiac rhythm management devices (P= 0.02). No difference was found between Main Regional Hospitals and Tertiary Cardiac Hospitals, 20 vs. 23%, respectively (NS). The prevalence of IE in high-risk patients with one or more predisposing condition or clinical evidence of IE were significantly higher compared with low-risk patients with no additional risk factors (38 vs. 5%; P < 0.001). IE was associated with a higher 6 months mortality, 14(26%) vs. 28(15%) in SAB patients without IE, respectively (P < 0.05). CONCLUSION SAB patients carry a high risk for development of IE, which is associated with a worse prognosis compared with uncomplicated SAB. The presenting symptoms and clinical findings associated with IE are often non-specific and echocardiography should always be considered as part of the initial evaluation of SAB patients.

Future challenges and treatment of Staphylococcus aureus bacteremia with emphasis on MRSA

Staphylococcus aureus bacteremia (SAB) is an urgent medical problem due to its growing frequency and its poor associated outcome. As healthcare delivery increasingly involves invasive procedures and implantable devices, the number of patients at risk for SAB and its complications is likely to grow. Compounding this problem is the growing prevalence of methicillin-resistant S. aureus (MRSA) and the dwindling efficacy of vancomycin, long the treatment of choice for this pathogen. Despite the recent availability of several new antibiotics for S. aureus, new strategies for treatment and prevention are required for this serious, common cause of human infection.

Enterococcus faecalis Infective Endocarditis A Pilot Study of the Relationship Between Duration of Gentamicin Treatment and Outcome

Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min (P=0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P<0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively (P=0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P=0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P=0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results.Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min ( P =0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P <0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively ( P =0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P =0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P =0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results. # Clinical Perspective {#article-title-50}

Major Cerebral Events in Staphylococcus Aureus Infective Endocarditis: Is Anticoagulant Therapy Safe?

Objectives: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). Methods: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset of admission and during hospitalization. Results: Overall, 70 out of 175 patients (40%; 95% CI: 33–47%) experienced major cerebral events during the course of the disease, cerebral ischaemic stroke occured in 59 patients (34%; 95% CI: 27–41%), cerebral infection in 23 patients (14%; 95% CI: 9–19%), and cerebral haemorrhage in 5 patients (3%; 95% CI: 0.5–6%). Patients receiving anticoagulation were less likely to have experienced a major cerebral event at the time of admission (15%) compared with those without anticoagulation (37%, p = 0.009; adjusted OR: 0.27; 95% CI: 0.075–0.96; p = 0.04). In-hospital mortality was 23% (95% CI: 17–29%), and there was no significant difference between those with or without anticoagulation. Conclusions: We found no increased risk of cerebral haemorrhage in S. aureus IE patients receiving anticoagulation. Anticoagulation was associated with a reduced risk of cerebral events before initiation of antibiotics. Data support the continuance of anticoagulation in S. aureus IE patients when indicated.

The impact of cardiac surgery in native valve infective endocarditis: Can euroSCORE guide patient selection?

BACKGROUND Decision making regarding surgical intervention in native valve endocarditis (NVE) is often complex and surgery is withheld in a number of patients either because medical treatment is considered the best treatment or because the risk of operation is considered too high. The objective of this study was to investigate the outcome of surgical treatment and to validate the ability of euroSCORE to predict operative mortality in NVE patients. METHODS Prospective cohort study including 323 consecutive NVE patients. Patients were divided into 3 groups based on treatment strategy and indication/contraindication for surgery. The additive and logistic euroSCORE was calculated and the observed and predicted mortality was compared. RESULTS Cardiac surgery was associated with a good prognosis, in-hospital and after 12months, compared to conservative treatment. After adjustment for confounders surgery was associated with a survival benefit (hazard ratio (HR) 0.45, 95% CI: 0.27-0.76%; p=0.003). When propensity score was used in regression adjustment, cardiac surgery was still associated with a better outcome after 12months (HR 0.41, 95% CI: 0.25-0.68; p<0.001). Observed mortality for patients receiving surgical treatment was 11% compared to a mean logistic euroSCORE mortality of 16% (NS). The discriminating ability of euroSCORE was good, area under the ROC curve 0.74 (95% CI: 0.64-0.84; p<0.001) logistic model and 0.75 (95% CI: 0.65-0.86; p<0.001) additive model. CONCLUSIONS Cardiac surgery was associated with a good prognosis when indicated regardless of euroSCORE, and surgery should only be withheld after thorough consideration. EuroSCORE remains a valuable tool to identify high-risk IE patients when surgery is considered.

Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis.

Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective cohort study, the CVC incidence was compared between NVE patients with and without ongoing warfarin. Among 587 NVE episodes, 48 (8%) occurred in patients on warfarin. A symptomatic CVC was seen in 144 (25%) patients, with only three on warfarin. CVC were significantly less frequent in patients on warfarin (6% vs. 26%, odds ratio [OR] 0.20, 95% confidence interval [CI] 0.06–0.6, p = 0.006). No increase in haemorrhagic lesions was detected in patients on warfarin. Staphylococcus aureus aetiology (adjusted OR [aOR] 6.3, 95% CI 3.8–10.4) and vegetation length (aOR 1.04, 96% CI 1.01–1.07) were risk factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07–0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1–0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01–0.79) correlated with lower CVC frequency.

Anticoagulation in Patients With Stroke With Infective Endocarditis Is Safe

### The Case: A 33-year-old man with a prosthetic mitral valve presents with an occipital infarct, fever, and leukocytosis. Work-up confirms the diagnosis of infective endocarditis due to Staphylococcus aureus. Cardiovascular surgeons recommend anticoagulation and urgent valve replacement. ### The Questions: ### The Controversy: The use of anticoagulation in stroke patients with infective endocarditis. Anticoagulation is a controversial issue in Staphylococcus aureus infective endocarditis (IE) because these patients are believed to be particularly susceptible to hemorrhagic transformation of embolic lesions. However, the evidence supporting the deleterious effect of anticoagulation is at best incomplete and the adverse effect of such treatment has been questioned by most recent research. An increasing number of patients with IE receive anticoagulant treatment because of mechanical prosthetic valves, atrial fibrillation, pulmonary embolism, and factor V Leiden mutation as well as other hypercoagulability disorders. These patients carry an increased risk of thromboembolism and the decision to terminate anticoagulant treatment should therefore balance the risks …

The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis

Abstract Background: Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate. Methods: In a prospective cohort study in Sweden and Demark, the influence of previously established antiplatelet therapy on CVC incidence and mortality in IE was assessed using logistic regression models. Results: Among 684 left-sided definite IE episodes, 23.0% were seen in patients on established antiplatelet therapy (96% acetylsalicylic acid). Patients on antiplatelet therapy were older and significantly more often had a history of congestive heart failure prior to IE diagnosis. No difference in CVC rate was seen between patients with and without ongoing antiplatelet therapy (23.6% vs 25.0%, adjusted odds ratio (AOR) 0.8, 95% confidence interval (CI) 0.48–1.5). Ischemic stroke, which occurred in 115 episodes (16.8%), was the most common cerebral lesion, and haemorrhagic complications were seen in 16 (2.3%) patients without correlation to chronic antiplatelet therapy. Unadjusted 1-y mortality was higher for patients on previously established antiplatelet therapy (33.8% vs 24.1%, odds ratio (OR) 1.6, 95% CI 1.1–2.4), but after adjustment for covariables associated with mortality an opposite statistical trend was seen (AOR 0.7, 95% CI 0.4–1.1). Conclusions: The incidence of symptomatic CVC in IE patients was not reduced by previously established antiplatelet therapy. One-y mortality was higher in patients on antiplatelet therapy in univariate analysis, but after multivariable modelling this association was lost.

One-year mortality in coagulase-negative Staphylococcus and Staphylococcus aureus infective endocarditis.

The aim of this study was to investigate in-hospital mortality and 12-month mortality in patients with coagulase-negative Staphylococcus (CoNS) compared to Staphylococcus aureus (S. aureus) infective endocarditis (IE). We used a prospective cohort study of 66 consecutive CoNS and 170 S. aureus IE patients, collected at 2 tertiary university hospitals in Copenhagen (Denmark) and at 1 tertiary university hospital in Gothenburg (Sweden). Median (range) C-reactive protein at admission was higher in patients with S. aureus IE (150 mg/l (1–521) vs 94 mg/l (6–303); p<0.001), which may suggest a more serous infection. CoNS was associated with prosthetic valve IE (49% vs 24%; p<0.001) and median diagnostic delay was longer in CoNS IE patients (20 d (0–232) vs 9 d (0–132); p<0.001). In-hospital mortality was equally high in both groups but 25% of the CoNS IE patients had died after 1 y compared to 39% of patients with S. aureus IE (p =0.05). In conclusion, CoNS IE was associated with a long diagnostic delay and high in-hospital mortality, whereas post-discharge prognosis was better in this group of patients compared to patients with IE due to S. aureus.

Enterococcus faecalis Infective EndocarditisClinical Perspective

Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min (P=0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P<0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively (P=0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P=0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P=0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results.Background— Because of the nephrotoxic effects of aminoglycosides, the Danish guidelines on infective endocarditis were changed in January 2007, reducing gentamicin treatment in enterococcal infective endocarditis from 4 to 6 weeks to only 2 weeks. In this pilot study, we compare outcomes in patients with Enterococcus faecalis infective endocarditis treated in the years before and after endorsement of these new recommendations. Methods and Results— A total of 84 consecutive patients admitted with definite left-sided E faecalis endocarditis in the period of 2002 to 2011 were enrolled. Forty-one patients were treated before and 43 patients were treated after January 1, 2007. There were no significant differences in baseline characteristics. At hospitalization, the 2 groups had similar estimated glomerular filtration rates of 66 and 75 mL/min ( P =0.22). Patients treated before January 2007 received gentamicin for a significantly longer period (28 versus 14 days; P <0.001). The primary outcome, 1-year event-free survival, did not differ: 66% versus 69%, respectively ( P =0.75). At discharge, the patients treated before 2007 had a lower estimated glomerular filtration rate (45 versus 66 mL/min; P =0.008) and a significantly greater decrease in estimated glomerular filtration rate (median, 11 versus 1 mL/min; P =0.009) compared with those treated after 2007. Conclusions— Our present pilot study suggests that the recommended 2-week treatment with gentamicin seems adequate and preferable in treating non–high-level aminoglycoside-resistant E faecalis infective endocarditis. The longer duration of gentamicin treatment is associated with worse renal function. Although the certainty of the clinical outcomes is limited by the sample size, outcomes appear to be no worse with the shorter treatment duration. Randomized, controlled studies are warranted to substantiate these results. # Clinical Perspective {#article-title-50}