Conventional therapy and new antifungal drugs against Malassezia infections.

Malassezia yeasts are commensal microorganisms occurring on the skin of humans and animals causing dermatological disorders or systemic infections in severely immunocompromised hosts. Despite attempts to control such yeast infections with topical and systemic antifungals, recurrence of clinical signs of skin infections as well as treatment failure in preventing or treating Malassezia furfur fungemia have been reported most likely due to wrong management of these infections (e.g., due to early termination of treatment) or due to the occurrence of resistant phenomena. Standardized methods for in vitro antifungal susceptibility tests of these yeasts are still lacking, thus resulting in variable susceptibility profiles to azoles among Malassezia spp. and a lack of clinical breakpoints. The inherent limitations to the current pharmacological treatments for Malassezia infections both in humans and animals, stimulated the interest of the scientific community to discover new, effective antifungal drugs or substances to treat these infections. In this review, data about the in vivo and in vitro antifungal activity of the most commonly employed drugs (i.e., azoles, polyenes, allylamines, and echinocandins) against Malassezia yeasts, with a focus on human bloodstream infections, are summarized and their clinical implications are discussed. In addition, the usefulness of alternative compounds is discussed.

Malassezia ecology, pathophysiology, and treatment.

Malassezia are lipid dependent basidiomycetous yeasts that inhabit the skin and mucosa of humans and other warm-blooded animals, and are a major component of the skin microbiome. They occur as skin commensals, but are also associated with various skin disorders and bloodstream infections. The genus currently comprises 17 species and has recently been assigned its own class, Malasseziomycetes. Importantly, multiple Malassezia species and/or genotypes may cause unique or similar pathologies and vary in their antifungal susceptibility. In addition to culture-based approaches, culture-independent methods have added to our understanding of Malassezia presence and abundance and their relationship to pathogenicity. Moreover, these novel approaches have suggested a much wider-spread presence, including other human body parts and even other ecosystems, but their role in these arenas requires further clarification. With recent successful transformation and genetic engineering of Malassezia, the role of specific genes in pathogenesis can now be studied. We suggest that characterizing the metabolic impact of Malassezia communities rather than species identification is key in elucidation of pathophysiological associations. Finally, the increasing availability of genome sequences may provide key information aiding faster diagnostics, and understanding of the biochemical mechanisms for Malassezia skin adaptation and the design of future drugs.