Current and future approaches to antimycotic treatment in the era of resistant fungi and immunocompromised hosts.

Due to the ever-increasing number of immunocompromised patients, both localised and life-threatening systemic fungal infections are on the increase. Conventional treatment is of limited help, not in the least due to a less optimum benefit-to-risk ratio. Moreover, emerging pathogens with reduced antimicrobial susceptibility and the development of resistance in Candida albicans form a new challenge. Fortunately, conventional antimycotics have been improved and entirely new ones are on the horizon as well as alternative approaches such as immunoreconstitution.

Secreted aspartic proteinase (Sap) activity contributes to tissue damage in a model of human oral candidosis.

Secreted aspartic proteinases (Saps) are important virulence factors during Candida albicans mucosal or disseminated infections. A differential expression of individual SAP genes has been shown previously in a model of oral candidosis based on reconstituted human epithelium (RHE), and in the oral cavity of patients. In this study, the ultrastructural localization of distinct groups of Sap isoenzymes expressed during RHE infection was shown by immunoelectron microscopy using specific polyclonal antibodies directed against the gene products of SAP1-3 and SAP4-6. Large amounts of Sap1-3 antigen were found within C. albicans yeast and hyphal cell walls, often predominantly in close contact with epithelial cells, whereas lower quantities of Sap4-6 were detected in hyphal cells. To elucidate the relevance of the expressed Saps during oral infections, we examined the effect of the aspartic proteinase inhibitor, pepstatin A, during infection of the RHE. The extent of lesions caused by the strain SC5314 was found to be strongly reduced by the inhibitor, indicating that proteinase activity contributes to tissue damage in this model. To clarify which of the SAP genes are important for tissue necrosis, the histology of RHE infection with Deltasap1, Deltasap2, Deltasap3, Deltasap4-6 and three Deltasap1/3 double mutants were examined. Although tissue damage was not blocked completely with these mutants, an attenuated phenotype was observed for each of the single sap null mutants, and was more strongly attenuated in the Deltasap1/3 double null mutants. In contrast, the lesions caused by the Deltasap4-6 triple mutant were at least as severe as those caused by SC5314. During infection with the mutants, we observed that the SAP gene expression pattern of the Deltasap1 and the Deltasap1/3 mutants was altered in comparison with the wild-type strain. Expression of SAP5 was observed only during infection with the Deltasap1/3 mutant, whereas upregulation of SAP2 and SAP8 transcripts was observed in the Deltasap1 and the Deltasap1/3 mutants. These results suggest that Sap1-3, but not Sap4-6, contribute to tissue damage in this model. Furthermore, C. albicans may compensate for the deletion of certain SAP genes by upregulation of alternative SAP genes.

Identification of dermatophytes by Fourier transform infrared spectroscopy (FT-IR).

Fourier transform infrared spectroscopy is an established method in the routine diagnosis of various micro-organisms, including bacteria and yeasts, on a species level. Its possible value in the diagnostics of dermatophytes was analysed using three clinical isolates each of the three most frequently found species, namely Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum canis. The results encourage further work to establish a library which would allow the use of this method in the clinical setting. This might help to make repeated subcultures, which are money- and time-consuming, redundant.

[Review article. Molecular basis of antimycotic therapy]. / Ubersichtsartikel. Molekulare Grundlagen der antimykotischen Therapie.

A review is presented on the hitherto clinically administered antimycotic drugs, their action mechanisms and limitations as well as on the presently newly developed antifungals and their molecular targets.

Aquarium dermatitis: cercarial dermatitis in an aquarist.

A 33-year-old man presented with very itchy red papules on the back of his hands and forearms. These papules appeared about 90 min after he had cleaned his aquarium in which he kept native fish and watersnails. He had obtained the watersnails some weeks before from a nearby pond. Examination of water from the aquarium revealed cercariae. The clinical diagnosis of cercarial dermatitis was corroborated. Cercarial dermatitis has repeatedly been seen in swimmers but not in aquarists keeping fish in a home aquarium.

[Tinea in glabrous skin: total quality management]. / Tinea der freien Haut: Gütegesichertes Management.

Today tinea of glabrous skin still is one of the central diagnostic and therapeutic problems in dermatology. The choice of the adequate treatment is always influenced by the type of microorganism, the site of manifestation, time course and severity of the infection as well as by the immune status of the patient. Tinea has to be differentiated from other skin diseases. Thus, general guide lines for diagnostic processing are needed. Adequate treatment with various types of antimycotics either is topical or--less frequently--systemic.