Univ.-Prof. Dr. Cornelia LASS-FLÖRL
Medizinische Universität Innsbruck, Abteilung für Hygiene und Medizinische Mikrobiologie

Datum: Montag, 10. März 2014
Zeit: 17:00 Uhr
Ort: NW Fakultät, Erdgeschoß, Grüner Hörsaal (403), Hellbrunnerstraße 34, 5020 Salzburg 

Abstract
Over the last decade, there have been changes in the epidemiology of fungal infections as well as dramatic improvements in the antifungal armamentarium. Candida species are an increasingly important cause of infection among patients in intensive care units. Mold infections continue to occur predominantly among highly immunosuppressed patients, such as those who have acute leukemia and those undergoing hematopoietic stem cell or solid organ transplantation. Aspergillus species remain the most common molds to cause invasive infection, but other environmental molds, such as Scedosporium, Fusarium, and various mucormycetes, including Rhizopus and Mucor, appear to be increasing in some medical centers.  Aspergillus species are ubiquitous molds found in organic matter and the majority of human illness is caused by Aspergillus fumigatus. The transmission of fungal spores to the human host is via inhalation. Aspergillus causes a spectrum of disease, from colonization to hypersensitivity reactions to chronic necrotizing infections to rapidly progressive angioinvasion, often resulting in death. Invasive aspergillosis is a rapidly progressive, often fatal infection that occurs in patients who are severely immunosuppressed. Human host defense against the inhaled spores begins with the mucous layer and the ciliary action in the respiratory tract. Macrophages and neutrophils encompass, engulf, and eradicate the fungus. However, many fungi produce toxic metabolites that inhibit macrophage and neutrophil phagocytosis. Corticosteroids also impair macrophage and neutrophil function. Underlying immunosuppression (eg, HIV disease, chronic granulomatous disease, pharmacologic immunosuppression) also contributes directly to neutrophil dysfunction or decreased numbers of neutrophils. In individuals who are immunosuppressed, vascular invasion is much more common and may lead to infarction, hemorrhage, and necrosis of lung tissue. Invasive fungal infections are associated with significant mortality, with a rate of 30-95%. The treatment requires intravenous antifungal therapy with Voriconazole being used as first-line therapy. The increasing role of azoles might be threatened by the acquisition of resistance by opportunistic moulds. Evolution of drug resistance seems to be less prominent in fungi than in bacteria, in which horizontal transfer of genes and accessory genetic elements across taxa provides a major source of genetic variation. In fungi, the evolution of drug resistance is more likely to proceed by the sequential accumulation of adaptive mutations. We recently face the rapid emergence of azole resistance in A. fumigatus isolates cultured from patients with invasive aspergillosis. Azole resistance in Aspergillus fumigatus may be due to a side-effect of environmental fungicide use.