Systemic mycosis caused by a new Cladophialophora species.

A 22-year-old woman suffered from haemoptyses of unknown aetiology. A tumour in the lingula was diagnosed histologically to be a granulomatosis, most likely a sarcoidosis. Two years later, the patient returned with dyspnoea caused by a granulomatous tumour in the trachea, histologically similar to that seen earlier. After bronchoscopic laser resection, cortisone therapy was applied but without success. A fungus was subsequently discovered histologically and was cultivated from biopsy specimens. Retrospective research of primary histological slides led to the conclusion that a mycosis was the initial cause of the tumours. The mycosis was successfully treated with high-dose itraconazole for 1 year, combined with 5-fluorocytosine (5-FC) during the first few months. The causative agent was found to be a new species of Cladophialophora, and is described as C. arxii Tintelnot; its key characteristics are presented.

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm; extracytoplasmic membrane vesicles are formed and deposited in the cell wall; starved fungal cells, with normal ultrastructure, can be found; lysed, dead cells demonstrate the process of severe ultrastructural damage; T. mentagrophytes cell walls especially increase in thickness. The extent of the damage caused by amorolfine is comparable to that produced by azole antifungals.

Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes.

Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm. Extracytoplasmic membrane vesicles are formed and deposited in the cell wall. Starved fungal cells, with normal ultrastructure, can be found. Lysed, dead cells demonstrate the process of severe ultrastructural damage. T. mentagrophytes cell walls especially increase in thickness. The feature of the damage caused by amorolfine is comparable to that produced by azole antifungals.

Protective effect of human granulocyte colony-stimulating factor (hG-CSF) on Cryptococcus and Aspergillus infections in normal and immunosuppressed mice.

Prophylactic treatment with human granulocyte colony-stimulating factor (hG-CSF) affords significant protection against systemic aspergillosis or pulmonary aspergillosis in neutropenic (cyclophosphamide-treated) mice but not in cortisone-treated animals. Cryptococcosis does not respond to hG-CSF therapy. Our data show that granulocytes play an important role in the immune defense against aspergillosis, but not against cryptococcosis. Combined treatment using hG-CSF and conventional antimycotics shows a significant beneficial effect in systemic or pulmonary aspergillosis.

Protective effect of human granulocyte colony stimulating factor (hG-CSF) on Candida infections in normal and immunosuppressed mice.

Prophylactic treatment with human granulocyte colony stimulating factor (hG-CSF) affords significant protection against systemic infections caused by C. albicans in cyclophosphamide-treated but not in cortisone-treated mice. Localized candidosis in neutropenic mice does not respond to hG-CSF. Our data show that granulocytes play an important role in the immune defence against deep mycoses, but not against local infections. From our data it is reasonable to assume that prophylactic treatment with hG-CSF may augment the resistance of immunosuppressed patients to deep Candida infection, but it would be of little help against oral candidosis of HIV patients.

The medically important dematiaceous fungi and their identification.

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).

[The resistance behavior of yeast isolates from defined patient groups to 5-fluorocytosine]. / Das Resistenzverhalten von Sprosspilzisolaten aus definierten Probandengruppen gegenüber 5-Fluorcytosin.

Susceptibility and development of resistance to 5-FC in Candida strains isolated from 4 defined groups of probands was investigated. 5-FC-susceptibility was determined in a microdilution assay in yeast nitrogen base after 24 h incubation at 37 degrees C. The range investigated ranked between 5-FC-concentrations from 0.015-16 microgram ml-1. Isolates with an MIC of greater than or equal to 16 micrograms ml-1 were regarded as 5-FC-resistant. In total 336 Candida isolates were investigated; 21 of them (= 6.3%) were found to be 5-FC-resistant. The Candida isolates were rather different with respect of their origin: 57 vaginal isolates from non-risk patients from Southern Germany comprised 5.3% 5-FC-resistant strains. 160 isolates from the urine of longtime-intensive care patients of total Germany were 5-FC-resistant with 6.3%. Of 74 isolates of different localization from intensive care patients of the University Clinics in Freiburg 10.8% were 5-FC-resistant. Among 45 isolates from the oral cavity from HIV-positive patients of the Frankfurt region no 5-FC-resistant strain was found. The epidemiology of 5-FC-resistance is mainly based on the percentage of non-albicans isolates of the proband groups (C. tropicalis, C. krusei and others), and is less based on the frequency of C. albicans serotype B isolates. In sequential observations with individual intensive care patients no increase of 5-FC-resistance in their Candida isolates could be observed with longer periods of hospitalization.

Effect of oxiconazole and Ro 14-4767/002 on sterol pattern in Candida albicans.

The effect of the imidazole oxiconazole and the morpholine derivative Ro 14-4767/002 on the sterol metabolism of Candida albicans was investigated at different periods of growth. Ergosterol, representing the main sterol component of control cells, was markedly reduced in oxiconazole-treated and Ro 14-4767/002-treated cells. However, the total sterol content of the cells treated with both drugs was increased due to accumulation of other sterols not present in control cells: in oxiconazole-treated cells 24-methenedihydrolanosterol, 4,14-dimethylfecosterol and 14-methylfecosterol accumulated, indicating an inhibition of C14-demethylation. This is in agreement with the mode of action described for other azoles in various pathogen fungi. In Ro 14-4767/002-treated cells the main sterol accumulated was ignosterol, indicating an inhibition of delta 14-sterol reductase and delta 8-delta 7-isomerase. This inhibition has not been described before in human pathogens although it has been previously found in plant pathogenic fungi treated with fenpropimorph.