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      Prognostic factors and historical trends in the epidemiology of candidemia in critically ill patients: an analysis of five multicenter studies sequentially conducted over a 9-year period

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          Abstract

          Purpose

          To describe temporal trends in the epidemiology, clinical management and outcome of candidemia in intensive care unit (ICU) patients.

          Methods

          This study was a retrospective analysis of 1,392 episodes of candidemia in 647 adult ICU patients from 22 Brazilian hospitals. The characteristics of candidemia in these ICU patients were compared in two periods (2003–2007, period 1; 2008–2012, period 2), and the predictors of 30-day mortality were assessed.

          Results

          The proportion of patients who developed candidemia while in the ICU increased from 44 % in period 1 to 50.9 % in period 2 ( p = 0.01). Prior exposure to fluconazole before candidemia (22.3 vs. 11.6 %, p < 0.001) and fungemia due to Candida glabrata (13.1 vs. 7.8 %, p = 0.03) were more frequent in period 2, as was the proportion of patients receiving an echinocandin as primary therapy (18.0 vs. 5.9 %, p < 0.001). The 30-day mortality rate decreased from 76.4 % in period 1 to 60.8 % in period 2 ( p < 0.001). Predictors of 30-day mortality by multivariate analysis were older age, period 1, treatment with corticosteroids and higher APACHE II score, while treatment with an echinocandin were associated with a higher probability of survival.

          Conclusions

          We found a clear change in the epidemiology and clinical management of candidemia in ICU patients over the 9-year period of the study. The use of echinocandins as primary therapy for candidemia appears to be associated with better outcomes.

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          Most cited references26

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          Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study.

          Inadequate antimicrobial treatment is an independent determinant of hospital mortality, and fungal bloodstream infections are among the types of infection with the highest rates of inappropriate initial treatment. Because of significant potential for reducing high mortality rates, we sought to assess the impact of delayed treatment across multiple study sites. The goals our analyses were to establish the frequency and duration of delayed antifungal treatment and to evaluate the relationship between treatment delay and mortality. We conducted a retrospective cohort study of patients with candidemia from 4 medical centers who were prescribed fluconazole. Time to initiation of fluconazole therapy was calculated by subtracting the date on which fluconazole therapy was initiated from the culture date of the first blood sample positive for yeast. A total of 230 patients (51% male; mean age +/- standard deviation, 56 +/- 17 years) were identified; 192 of these had not been given prior treatment with fluconazole. Patients most commonly had nonsurgical hospital admission (162 patients [70%]) with a central line catheter (193 [84%]), diabetes (68 [30%]), or cancer (54 [24%]). Candida species causing infection included Candida albicans (129 patients [56%]), Candida glabrata (38 [16%]), Candida parapsilosis (25 [11%]), or Candida tropicalis (15 [7%]). The number of days to the initiation of antifungal treatment was 0 (92 patients [40%]), 1 (38 [17%]), 2 (33 [14%]) or > or = 3 (29 [12%]). Mortality rates were lowest for patients who began therapy on day 0 (14 patients [15%]) followed by patients who began on day 1 (9 [24%]), day 2 (12 [37%]), or day > or = 3 (12 [41%]) (P = .0009 for trend). Multivariate logistic regression was used to calculate independent predictors of mortality, which include increased time until fluconazole initiation (odds ratio, 1.42; P < .05) and Acute Physiology and Chronic Health Evaluation II score (1-point increments; odds ratio, 1.13; P < .05). A delay in the initiation of fluconazole therapy in hospitalized patients with candidemia significantly impacted mortality. New methods to avoid delays in appropriate antifungal therapy, such as rapid diagnostic tests or identification of unique risk factors, are needed.
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            Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.

            Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy. We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes. Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point. Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.
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              Anidulafungin versus fluconazole for invasive candidiasis.

              Anidulafungin, a new echinocandin, has potent activity against candida species. We compared anidulafungin with fluconazole in a randomized, double-blind, noninferiority trial of treatment for invasive candidiasis. Adults with invasive candidiasis were randomly assigned to receive either intravenous anidulafungin or intravenous fluconazole. All patients could receive oral fluconazole after 10 days of intravenous therapy. The primary efficacy analysis assessed the global response (clinical and microbiologic) at the end of intravenous therapy in patients who had a positive baseline culture. Efficacy was also assessed at other time points. Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a "center effect"; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, -1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P=0.13). Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. (ClinicalTrials.gov number, NCT00056368 [ClinicalTrials.gov]). Copyright 2007 Massachusetts Medical Society.
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                Author and article information

                Contributors
                55-11-55764985 , arnaldolcolombo@gmail.com
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                1 August 2014
                1 August 2014
                2014
                : 40
                : 10
                : 1489-1498
                Affiliations
                [ ]Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
                [ ]Hospital do Servidor Público Estadual de São Paulo, São Paulo, Brazil
                [ ]Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, Brazil
                [ ]Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
                [ ]Universidade Federal do Paraná, Curitiba, Brazil
                [ ]Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
                [ ]Rua Pedro de Toledo, 669, 04039-032 São Paulo, SP Brazil
                Article
                3400
                10.1007/s00134-014-3400-y
                4176831
                25082359
                5611c7eb-b339-4165-9fcf-93a2e0673a18
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 8 May 2014
                : 6 July 2014
                Categories
                Original
                Custom metadata
                © Springer-Verlag Berlin Heidelberg and ESICM 2014

                Emergency medicine & Trauma
                candidemia,mortality,antifungal therapy,echinocandin,invasive candidiasis

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