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      VRE and VSE Bacteremia Outcomes in the Era of Effective VRE Therapy: A Systematic Review and Meta-analysis

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          Abstract

          BACKGROUND

          Prior data suggest that vancomycin-resistant Enterococcus (VRE) bacteremia is associated with worse outcomes than vancomycin-sensitive Enterococcus (VSE) bacteremia. However, many studies evaluating such outcomes were conducted prior to the availability of effective VRE therapies.

          OBJECTIVE

          To systematically review VRE and VSE bacteremia outcomes among hospital patients in the era of effective VRE therapy.

          METHODS

          Electronic databases and grey literature published between January 1997 and December 2014 were searched to identify all primary research studies comparing outcomes of VRE and VSE bacteremias among hospital patients, following the availability of effective VRE therapies. The primary outcome was all-cause, in-hospital mortality, while total hospital length of stay (LOS) was a secondary outcome. All meta-analyses were conducted in Review Manager 5.3 using random-effects, inverse variance modeling.

          RESULTS

          Among all the studies reviewed, 12 cohort studies and 1 case control study met inclusion criteria. Similar study designs were combined in meta-analyses for mortality and LOS. VRE bacteremia was associated with increased mortality compared with VSE bacteremia among cohort studies (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.38–2.35; I 2=0%; n=11); the case-control study estimate was similar, but not significant (OR, 1.93; 95% CI, 0.97–3.82). LOS was greater for VRE bacteremia patients than for VSE bacteremia patients (mean difference, 5.01 days; 95% CI, 0.58–9.44]; I 2=0%; n=5).

          CONCLUSIONS

          Despite the availability of effective VRE therapy, VRE bacteremia remains associated with an increased risk of in-hospital mortality and LOS when compared to VSE bacteremia.

          Infect. Control Hosp. Epidemiol. 2015;37(1):26–35

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          Most cited references20

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          Vancomycin-resistant enterococcal infections.

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            The inclusion of reports of randomised trials published in languages other than English in systematic reviews.

            To assemble a large dataset of language restricted and language inclusive systematic reviews, including both conventional medicinal (CM) and complementary and alternative medicine (CAM) interventions. To then assess the quality of these reports by considering and comparing different types of systematic reviews and their associated RCTs; CM and CAM interventions; the effect of language restrictions compared with language inclusions, and whether these results are influenced by other issues, including statistical heterogeneity and publication bias, in the systematic review process. MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Centralised Information Service for Complementary Medicine. Three types of systematic reviews were included: language restricted; language inclusive/English language (EL) reviews that searched RCTs in languages other than English (LOE) but did not find any and, hence, could not include any, in the quantitative data synthesis; and systematic reviews that searched for RCTs in LOE and included them in the quantitative data synthesis. Fisher's exact test was applied to compare the three different types of systematic reviews with respect to their reporting characteristics and the systematic review quality assessment tool. The odds ratio of LOE trials versus EL trials was computed for each review and this information was pooled across the reviews to examine the influence that language of publication and type of intervention (CM, CAM) have on the estimates of intervention effect. Several sensitivity analyses were performed. The LOE RCTs were predominantly in French and German. Language inclusive/LOE systematic reviews were of the highest quality compared with the other types of reviews. The CAM reviews were of higher quality compared with the CM reviews. There were only minor differences in the quality of reports of EL RCTs compared with the eight other languages considered. However, there are inconsistent differences in the quality of LOE reports depending on the intervention type. The results, and those reported previously, suggest that excluding reports of RCTs in LOE from the analytical part of a systematic review is reasonable. Because the present research and previous efforts have not included every type of CM RCT and the resulting possibility of the uncertainty as to when bias will be present by excluding LOE, it is always prudent to perform a comprehensive search for all evidence. This result only applies to reviews investigating the benefits of CM interventions. This does not imply that systematic reviewers should neglect reports in LOE. We recommend that systematic reviewers search for reports regardless of the language. There may be merit in including them in some aspects of the review process although this decision is likely to depend on several factors, including fiscal and other resources being available. Language restrictions significantly shift the estimates of an intervention's effectiveness when the intervention is CAM. Here, excluding trials reported in LOE, compared with their inclusion, resulted in a reduced intervention effect. The present results do not appear to be influenced by statistical heterogeneity and publication bias. With the exception of CAM systematic reviews, the quality of recently published systematic reviews is less than optimal. Language inclusive/LOE systematic reviews appear to be a marker for a better quality systematic review. Language restrictions do not appear to bias the estimates of a conventional intervention's effectiveness. However, there is substantial bias in the results of a CAM systematic review if LOE reports are excluded from it.
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              Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization.

              Enterococci are a major cause of nosocomial bacteraemia. The impacts of vanB vancomycin resistance and antibiotic therapy on outcomes in enterococcal bacteraemia are unclear. Factors that affect length of stay (LOS) and costs of managing patients with enterococcal bacteraemia are also unknown. This study aimed to identify factors associated with mortality, LOS and hospitalization costs in patients with enterococcal bacteraemia and the impact of vancomycin resistance and antibiotic therapy on these outcomes. Data from 116 patients with vancomycin-resistant Enterococci (VRE), matched 1:1 with patients with vancomycin-susceptible Enterococcus (VSE), from two Australian hospitals were reviewed for clinical and economic outcomes. Univariable and multivariable logistic and quantile regression analyses identified factors associated with mortality, LOS and costs. Intensive care unit admission (OR, 8.57; 95% CI, 3.99-18.38), a higher burden of co-morbidities (OR, 4.55; 95% CI, 1.83-11.33) and longer time to appropriate antibiotics (OR, 1.02; 95% CI, 1.01-1.03) were significantly associated with mortality in enterococcal bacteraemia. VanB vancomycin resistance increased LOS (4.89 days; 95% CI, 0.56-11.52) and hospitalization costs (AU$ 28 872; 95% CI, 734-70 667), after adjustment for confounders. Notably, linezolid definitive therapy was associated with lower mortality (OR, 0.13; 95% CI, 0.03-0.58) in vanB VRE bacteraemia patients. In patients with VSE bacteraemia, time to appropriate antibiotics independently influenced mortality, LOS and hospitalization costs, and underlying co-morbidities were associated with mortality. The study findings highlight the importance of preventing VRE bacteraemia and the significance of time to appropriate antibiotics in the management of enterococcal bacteraemia. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.
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                Author and article information

                Journal
                Infect Control Hosp Epidemiol
                Infect Control Hosp Epidemiol
                ICE
                Infection Control and Hospital Epidemiology
                Cambridge University Press (New York, USA )
                0899-823X
                1559-6834
                05 October 2015
                January 2016
                : 37
                : 1
                : 26-35
                Affiliations
                [1 ]Infection Prevention and Control , Public Health Ontario, Toronto, Ontario, Canada
                [2 ]St. Joseph’s Health Centre , Toronto, Ontario, Canada
                [3 ]Department of Medicine, University of Toronto , Toronto, Ontario, Canada
                [4 ]Department of Medicine, University of Ottawa , Ottawa, Ontario, Canada
                [5 ]Ottawa Hospital Research Institute , Ottawa, Ontario, Canada
                Author notes
                Address correspondence to Jennie Johnstone, MD, PhD, Public Health Ontario, 480 University Avenue, Suite 300, Toronto ON M5G 1V2 ( jennie.johnstone@ 123456oahpp.ca )
                Article
                S0899823X15002287 00228
                10.1017/ice.2015.228
                4707508
                26434609
                f519c655-a469-41cf-a2eb-b0c6fb2547e6
                © © 2015 by The Society for Healthcare Epidemiology of America 2015

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 April 2015
                : 30 August 2015
                Page count
                Figures: 7, Tables: 2, Pages: 10
                Categories
                Original Articles

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