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 .).

Long-term Risk of Hemorrhagic Stroke in Patients With Infective Endocarditis: A Danish Nationwide Cohort Study.

Background: The present study aimed to investigate the long-term risk of hemorrhagic stroke (HS) in patients with infective endocarditis (IE). Methods: Using a register-based nationwide cohort of 9 million Danes, we performed propensity score matching between patients with left-sided IE from 1977 to mid-2015 and IE-free individuals (1:10). Follow-up started 1 year after the IE diagnosis. Hazard ratios (HRs) for HS in patients with IE compared with the matched cohort were estimated using Cox regression. Results: During follow-up of 5735 patients with left-sided IE from 1 year after IE diagnosis and up to 37.5 years (median, 6.3 years), 103 cases of HS were observed. Compared with the matched cohort, patients with IE had a higher long-term risk of HS (HR, 1.47; 95% confidence interval, 1.20-1.80; P < .001). The risk of HS was particularly increased in patients within the lowest propensity score quartile (HR, 2.60; 95% confidence interval, 1.89-3.58). Mediation analyses suggested that the increased HS risk could be explained by an indirect effect of mechanical heart valve insertion, atrial fibrillation, or treatment with anticoagulants. The cumulative risk of HS 30 years after start of follow-up was 3.0% in patients with IE. Conclusions: IE does not directly increase the long-term risk of HS. The apparent excess risk of HS in patients with previous IE was explained by mediating factors, including mechanical heart valve insertion, atrial fibrillation, and anticoagulation medication.

Plasma levels of glucagon but not GLP-1 are elevated in response to inflammation in humans.

OBJECTIVE: Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation. DESIGN: Prospective longitudinal cohort study. MATERIALS AND METHODS: We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n = 16), urosepsis (n = 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n = 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males. RESULTS: Glucagon and CRP were positively and significantly correlated (r = 0.27; P = 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P = 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P < 0.05) but not GLP-1. CONCLUSIONS: Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.