Scientific knowledge and technology will continue to rapidly expand, having a profound effect upon patient care and research. As economic resources become more limited, new strategies will be formulated leading to innovative management approaches based upon a clearer understanding of host-pathogen interactions. Information management and a strong scientific research infrastructure will provide the necessary foundation for new discoveries. Funding for applied and basic research will flow from academic-industry-government partnerships in various combinations.

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Topical treatment with an antifungal agent was performed in 70 cases of onychomycosis (69 cases of tinea unguium and 1 case of Candida onychomycosis). The patients were treated every night by occlusive dressing using bifonazole cream containing 40% urea, and then by simple application of 1% bifonazole solution in the morning. During the treatment period, the softened affected nails were removed as completely as possible with nail clippers and files. The nails were observed every two weeks, and the efficacy was evaluated after 12 weeks. Two cases were excluded and 28 cases dropped out leaving 40 cases for efficacy evaluation. Among the 40 patients, 20 appeared to be mycologically negative (mycological cure rate: 50.0%). Clinical response was judged by the changes in opacity and thickness of the nails. Nine patients were evaluated as showing “marked improvement” and 16 as showing “improvement” (improvement rate: 62.5%). Erosion was noted as an adverse reaction in 2 patients. In one patient, treatment was stopped and the lesion was improved by antibiotic ointment, and in another, treatment was resumed when erosion was cured by discontinuation of the treatment. These results suggest that the topical treatment of onychomycosis by occlusive dressing is a useful method for those patients who have difficulties in or do not wish to be treated with oral antifungal agents.

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Effects of itraconazole (ITCZ) on anti-Candida activity of a macrophage (MP)-neutrophil axis were examined in vitro. Murine peritoneal MP, stimulated by an enterococcal preparation FK-23, released tumor necrosis factor α (TNF) into the culture medium in 20hr-culture period. This level of TNF production by the stimulated MP, which were measured by a bioassay or immunological assay, was heightened by co-stimulation with 0.5μg/ml of ITCZ. Supernatants obtained from the culture medium of FK-23 and ITCZ-treated MP not only contained about 10ng/ml of TNF but also had the capacity to enhance anti-Candida activity of murine neutrophils. This enhancement was blocked by pretreatment of the MP-supernatant with anti-TNF antibody. Observation by scanning electron microscope suggested that cell walls of the candida mycelia, the growth of which was inhibited by the neutrophils in the presence of either the MP-supernatant or TNF, sustained similar structural damage. These results suggest that ITCZ augments anti-Candida activity of neutrophils through enhanced production of TNF by MP in vitro.

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The susceptibilities of clinical isolates of Candida spp. to fluconazole (FLCZ), itraconazole (ITCZ) and ketoconazole (KCZ) were determined by a new method, E-test (AB BIODISK, Sweden) and compared with those obtained by the microbroth dilution method. The MIC values of the 3 azoles obtained by the two methods were, in general, in good agreement. While MICs of FLCZ and KCZ demonstrated higher essential agreement rates and better correlation by both methods, MIC values of ITCZ by the E-test had a tendency to be higher than those of the microbroth dilution method in azole resistant strains.
Potential usability of E-test as a broth dilution method for susceptibility tests for clinically isolated Candida spp. including azole resistant strains was discussed.

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An 83-year-old man with aplastic anemia and steroid induced diabetes mellitus developed multiple nodules with pus on the back of his right hand and forearm. He had been treated with a daily dose of 30mg prednisolone for 2 months. These lesions had appeared a month before his visit. The histopathological findings revealed dermal abscesses containing hyphal structures, lymphocytes, histiocytes and giant cells. Grocott-Methenamine stain demonstrated abundant fungal elements. In culture, colonies grow rapidly and produce a white, cottony mycelium which later becomes gray in color. Microscopically, ovoid and pyriform conidia are produced at the ends of long slender conidiophores. On PCA agar, synnemata with small conidal heads developed at 37°C but cleistothecia did not appear. The patient did not respond to itraconazole therapy, however, with hyperthermic treatment, the eruptions gradually healed. Based on these findings, this fungal infection was diagnosed as pseudallescheriosis.

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