Infective Endocarditis

Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li-definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed. We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy. Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004). Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.