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Background: The optimal treatment for bloodstream infections (BSIs) with vancomycin-resistant enterococci (VRE) is unknown., Objective: This study examined outcomes in patients treated with daptomycin or linezolid for VRE BSI., Methods: A retrospective, multicenter, cohort study was performed via chart review. Hospitalized patients treated for VRE BSI with daptomycin or linezolid from September 1, 2003, to June 30, 2007, were identified via pharmacy and microbiology reports at each institution. Patients aged <18 years or with polymicrobial bacteremia were excluded from analysis. Linezolid and daptomycin were included because the participating institutions used either of the 2 agents as first-line treatment for VRE BSI. Univariate and multivariate analyses were performed to determine the effect of drug selection on mortality and duration of BSI. Duration of BSI was defined as the amount of time from the draw date of the first positive blood culture to the draw date of the first finalized negative blood culture. Adverse events were not assessed., Results: One-hundred one patients from 3 participating US hospitals experiencing VRE BSI were identified. Sixty-seven patients were treated with daptomycin and 34 with linezolid. Baseline characteristics appeared comparable between the daptomycin- and linezolidtreated groups, with the exception of shock (P = 0.049), prior vancomycin treatment (P = 0.002), and prior linezolid treatment (P < 0.001), all of which occurred significantly more often in daptomycin-treated patients. Inpatient mortality occurred in 31 daptomycin- and 10 linezolid-treated patients (46.3% vs 29.4%; P = NS). Linear regression found that shock (P = 0.015), infective endocarditis (P = 0.021), and concurrent rifampin or gentamicin treatment (P = 0.01) were associated with prolonged duration of positive cultures. Logistic regression revealed that shock (odds ratio [OR] = 14.24; P = 0.008), infection with Enterococcus faecium (OR = 53.10; P = 0.024), previous linezolid treatment (OR = 6.63; P = 0.031), concurrent rifampin or gentamicin treatment (OR = 6.48; P = 0.046), and a nonline source of infection (OR = 6.67; P = 0.019) were associated with increased mortality., Conclusions: In this retrospective cohort analysis, there were no significant differences in mortality of VRE BSI between patients receiving daptomycin or linezolid. Underlying comorbidities appeared to best predict outcome; however, given the retrospective nature of this study, larger, prospective, randomized, comparative studies are needed to control for potential biases and determine definitive outcome differences between these 2 antimicrobials., (Copyright © 2010 Excerpta Medica Inc. All rights reserved.)

Background: Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control., Objective: This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock., Methods: This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patient's hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol., Results: A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004)., Conclusion: Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution., (2010 Excerpta Medica Inc. All rights reserved.)