Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia - A prospective multicenter study

Background: Enterococcus species are major nosocomial pathogens and are exh ibiting vancomycin resistance with increasing frequency. Previous studies h ave not resolved whether vancomycin resistance Is an independent risk facto r for death in patients with invasive disease due to Enterococcus species o r whether antibiotic therapy alters the outcome of enterococcal bacteremia. Objective: To determine whether vancomycin resistance is an independent pre dictor of death in patients with enterococcal bacteremia and whether approp riate antimicrobial therapy influences outcome. Design: Prospective observational study. Setting: Four academic medical centers and a community hospital. Patients: All patients with enterococcal bacteremia. Measurements: Demographic characteristics; underlying disease; Acute Physio logy and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy duri ng the ensuing 6 weeks. The major end point was 14-day survival. Results: Of 398 episodes, 60% were caused by E. faecalis and 37% were cause d by E. faecium. Thirty-seven percent of isolates exhibited resistance or I ntermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previo us vancomycin use (odds ratio [OR], 5.82 [95% Cl, 3.20 to 10.58]; P < 0.001 ), previous corticosteroid use (OR, 2.43 [Cl, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [Cl, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [Cl, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [ Cl, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [Cl, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, rece ipt of effective antimicrobial therapy within 48 hours independently predic ted survival (OR for death, 0.21 [Cl, 0.06 to 0.80]; P = 0.02). Conclusions: vancomycin resistance is an independent predictor of death fro m enterococcal bacteremia. Early, effective antimicrobial therapy is associ ated with a significant improvement in survival.