Observational study of the epidemiology and outcomes of vancomycin-resistantEnterococcusbacteraemia treated with newer antimicrobial agents

Abstract

SUMMARY Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSI) are a growing problem with few clinical trials to guide therapy. We conducted a retrospective study of management and predictors of mortality for VRE-BSI at a tertiary care centre from January 2005 to August 2008. Univariate and multivariable analyses examined the relationship of patient characteristics and antibiotic therapy with 30-day all-cause mortality. Rates of VRE-BSI increased from 0.06 to 0.17 infections/thousand patient days (p=0.03). Among 235 patients, 30-day mortality was 34.9%. Patients were primarily treated with linezolid (44.2%) or daptomycin (36.5%). Factors associated with mortality were haemodialysis (OR 3.2, 95% CI 1.6-6.3, p=0.007), mechanical ventilation (OR 3.7, 95% CI 1.3-10.4, p=0.01), and malnutrition (OR 2.0, 95% CI 1.0-4.0, p=0.046). Use of linezolid, but not daptomycin (p=0.052) showed a trend toward an association with survival. In conclusion, VRE-BSI is a growing problem, associated with significant 30-day mortality. Multiple factors were associated with poor outcomes at our hospital.

Systematic Review and Meta-Analysis of Linezolid versus Daptomycin for Treatment of Vancomycin-Resistant Enterococcal Bacteremia

“…Eventually, 10 studies comparing the efficacy of daptomycin and linezolid for the treatment of VRE bacteremia were included in this systematic review and metaanalysis (5,6,(21)(22)(23)(24)(25)(26)(27)(28).…”

“…Vancomycin is the first-line treatment of BSIs caused by ampicillin-resistant enterococci; however vancomycin-resistant enterococci (VRE) nowadays account for approximately one-third of the enterococcal health care-associated infections in the United States (2) and for more than 20% of such infections in some European countries (3). Mortality rates in patients with VRE BSIs range between 20 and 46% (4)(5)(6). Patients with BSI due to VRE are 2.5 times more likely to die than patients with BSI due to vancomycin-susceptible strains (7).…”

“…According to the relevant clinical practice guidelines of the Infectious Diseases Society of America, linezolid or daptomycin is recommended for the treatment of catheter-related BSIs caused by ampicillin-and vancomycin-resistant enterococci (15). Limited data exist on the comparative efficacy of daptomycin versus linezolid for enterococcal bacteremias (5,6). Herein we summarize the available evidence and provide estimates of the clinical effectiveness of linezolid versus daptomycin for the treatment of VRE bacteremia by using meta-analytic methodology.…”

Evaluation of Standard- and High-Dose Daptomycin versus Linezolid against Vancomycin-Resistant Enterococcus Isolates in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

“…The simulated effective dose to achieve 80% maximal kill activity was 3 mg/kg for the two staphylococcal isolates (MICs of 0.125 and 0.25 g/ml) and 6.8 mg/kg for the two Enterococcus faecium isolates (MICs of 2 and 4 g/ml) (9). Based on the available data, the current Food and Drug Administration-approved dose of 6 mg/kg/day for Staphylococcus aureus bacteremia and right-sided infective endocarditis infections is likely suboptimal for infections caused by most enterococcus due to the higher MIC values and leads to the logical conclusion that higher daptomycin doses (i.e., Ͼ6 mg/kg/day) will be required to adequately treat these infections.Clinical experience with daptomycin for the treatment of enterococcal infections is limited to several retrospective, observational studies of patients with enterococcal bacteremia (12,14,17,18,20,21,28,29,31,32). Success rates in these series vary from 58.1% to 90% depending on the severity of illness of the included patients and the inclusion of clinical or microbiological results in the definition of success.…”

“…Clinical experience with daptomycin for the treatment of enterococcal infections is limited to several retrospective, observational studies of patients with enterococcal bacteremia (12,14,17,18,20,21,28,29,31,32). Success rates in these series vary from 58.1% to 90% depending on the severity of illness of the included patients and the inclusion of clinical or microbiological results in the definition of success.…”