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      Update on the treatment of disseminated fusariosis: Focus on voriconazole

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          Abstract

          Invasive fungal infections are a major cause of morbidity and mortality in immunocompromised patients, such as subjects with hematological malignancies and patients who underwent to hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). Fusarium spp. cause a broad spectrum of infections in humans. Immunologically competent hosts show mainly localized skin infections, whereas disseminated fusariosis occurs almost exclusively in immunocompromised patients. Fusarium spp. are resistant to many antifungal agents with equivocal in vitro and in vivo susceptibility to amphotericin B. Voriconazole (VRC) is a triazole shown to be safe, well tolerated, and in vitro efficacious against Fusarium spp. Although clinical experience is limited, many case reports have shown the efficacy of VRC in the treatment of fusariosis.

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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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            Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.

            Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B. Copyright 2002 Massachusetts Medical Society
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              Taxonomy, biology, and clinical aspects of Fusarium species.

              There are several taxonomic systems available for identifying Fusarium species. The philosophy used in each taxonomic system is discussed as well as problems encountered in working with Fusarium species in culture. Fusarium species are toxigenic, and the mycotoxins produced by these organisms are often associated with animal and human diseases. The implications for the association of the carcinogens, fumonisins, produced by Fusarium moniliforme and other Fusarium species with human diseases are discussed. Foreign-body-associated fusarial infection such as keratitis in contact lens wearers, onychomycosis, skin infections, and disseminated multiorgan infections are discussed. Disseminated fusarial hyalohyphomycosis has emerged as a significant, usually fatal infection in the immunocompromised host. Successful outcome is determined by the degree of immunosuppression, the extent of the infection, and the presence of a removable focus such as an indwelling central venous catheter. These infections may be clinically suspected on the basis of a constellation of clinical and laboratory findings, which should lead to prompt therapy, probably with one of the newer antifungal agents. Perhaps the use of such agents or the use of colony-stimulating factors may improve the outcome of this devastating infection. However, until new approaches for treatment develop, effective preventive measures are urgently needed.
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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 2007
                December 2007
                : 3
                : 6
                : 1165-1173
                Affiliations
                [1 ]Institute of Haematology and Clinical Oncology “Ariosto e Lorenzo Seràgnoli”, S. Orsola-Malpighi Hospital, University of Bologna Italy
                [2 ]Division of Infectious Diseases, S. Orsola-Malpighi Hospital, University of Bologna Italy
                Author notes
                Correspondence: Marta Stanzani “Lorenzo e Ariosto Serágnoli” Institute of Haematology and Clinical Oncology, Sant’Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, Padiglione 8, 40138, Bologna, Italy Tel +39 051 6363680 Fax +39 051 6364037 Email marta.stanzani2@ 123456unibo.it
                Article
                2387295
                18516266
                039f5e08-5c55-4ff3-a937-85988b37a4e8
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                Medicine
                fungal infections,immunocompromised patient,cancer,aspergillus,fusariosis,voriconazole
                Medicine
                fungal infections, immunocompromised patient, cancer, aspergillus, fusariosis, voriconazole

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