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      An observational efficacy and safety analysis of the treatment of acute invasive aspergillosis using voriconazole

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          Abstract

          The purpose of this study was to evaluate efficacy and safety of voriconazole in patients with acute invasive aspergillosis (IA) in a real-life, clinical setting. This was a multicenter observational study in adult patients treated with voriconazole for invasive mycosis. The study evaluated clinical response, mortality, use of other licensed antifungal therapy (OLAT), and treatment duration. This sub-analysis evaluated treatment and outcome data specifically from adult patients with proven/probable IA, while safety data were assessed in patients with proven/probable/possible IA. Of the 141 patients enrolled, 113 were adults with proven/probable IA and six had possible IA. Voriconazole treatment duration ranged from 1 to 183 days (median, 49.5 days). Voriconazole was used exclusively in 64% (72/113) of patients and in combination/sequentially with OLAT in 36%. Overall successful treatment response was 50% (57/113 patients). Twelve percent (14/113) of patients were switched to OLAT, either because of insufficient response (four patients) or for safety reasons (10 patients). Overall and attributable (entirely or partially due to fungal infection) mortality rates were 52% (59/113) and 17%, respectively. Treatment-related adverse events were reported for 18% (22/119) of patients. This observational study confirms the results of previous clinical trials demonstrating voriconazole as an effective and safe agent for treatment of confirmed acute IA.

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          Most cited references20

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          Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America.

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            Aspergillosis case-fatality rate: systematic review of the literature.

            To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.
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              Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients.

              Reports have focused on the emergence of moulds as pathogens in recipients of hematopoietic stem cell transplants. To review the incidence of and risks for mould infections, we examined the records of 5589 patients who underwent hematopoietic stem cell transplantation at the Fred Hutchinson Cancer Research Center (Seattle) from 1985 through 1999. After 1992, the incidence of invasive aspergillosis increased in allograft recipients and remained high through the 1990s. Infections with non-fumigatus Aspergillus species, Fusarium species, and Zygomycetes increased during the late 1990s, especially in patients who received multiple transplants. Although infection caused by Scedosporium species was common in patients who had neutropenia, infection caused by Zygomycetes typically occurred later after transplantation, when patients had graft-versus-host disease. The overall 1-year survival rate was equally poor (similar20%) for all patients with mould infections. The results of the present study demonstrate the changing epidemiology of mould infections, emphasizing the increasing importance of amphotericin B--resistant organisms and the differences in risks and outcome of infection with different filamentous fungi.
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                Author and article information

                Contributors
                frederique.jacobs@erasme.ulb.ac.be
                Journal
                Eur J Clin Microbiol Infect Dis
                Eur. J. Clin. Microbiol. Infect. Dis
                European Journal of Clinical Microbiology & Infectious Diseases
                Springer-Verlag (Berlin/Heidelberg )
                0934-9723
                1435-4373
                5 October 2011
                5 October 2011
                June 2012
                : 31
                : 6
                : 1173-1179
                Affiliations
                [1 ]Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
                [2 ]AZ Sint-Jan Hospital, Brugge, Belgium
                [3 ]Institut Bordet, Brussels, Belgium
                [4 ]Hôpital Universitaire de Mont-Godinne, Yvoir, Belgium
                [5 ]Antwerp University Hospital, Edegem, Belgium
                Article
                1425
                10.1007/s10096-011-1425-5
                3346940
                21971820
                a98fd4a5-769a-40c2-9d65-6f08e8905922
                © The Author(s) 2011
                History
                : 31 March 2011
                : 12 September 2011
                Categories
                Article
                Custom metadata
                © Springer-Verlag 2012

                Infectious disease & Microbiology
                medical microbiology,internal medicine,biomedicine
                Infectious disease & Microbiology
                medical microbiology, internal medicine, biomedicine

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