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      Multidisciplinary approach to the treatment of invasive fungal infections in adult patients. Prophylaxis, empirical, preemptive or targeted therapy, which is the best in the different hosts?

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          Abstract

          The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.

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          Most cited references 158

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          2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer.

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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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              Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study.

              To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                December 2008
                December 2008
                : 4
                : 6
                : 1261-1280
                Affiliations
                [1 ]Servicio de Medicina Intensiva, Hospital Universitario Dr Peset, Valencia, Spain;
                [2 ]Servicio de Microbiología;
                [3 ]Unidad de Enfermedades Infecciosas;
                [4 ]Unidad de Trasplante Pulmonar;
                [5 ]Servicio de Hematología;
                [6 ]Servicio de Farmacia;
                [7 ]Unidad de Microbiología Experimental, Centro de Investigación, Hospital Universitario La Fe Valencia, Spain
                Author notes
                Correspondence: Rafael Zaragoza, Servicio de Medicina Intensiva, Hospital Universitario Dr Peset, Av Gaspar Aguilar, 90, 46017 Valencia, Spain, Tel +34 9 6162 2569, Fax +34 9 6162 2501, Email zaragoza_raf@ 123456gva.es
                Article
                tcrm-4-1261
                2643107
                19337433
                © 2008 Zaragoza et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
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