We performed clinical studies on itraconazole, a new triazole antifungal agent. Four patients suffering from candidemia, pulmonary aspergillosis, oral thrush, and urinary tract infection due to Trichosporon cutaneum were treated with itraconazole at a single daily dose of 100-200 mg for 9-31 days. Clinical response was good in all patients. Bacteriological effect was eradicated in 2 cases, diminished in one and unknown in one. No side effect was observed and there were no abnormal laboratory findings. A suspected case of pulmonary cryptococcosis tolerated longterm administration of itraconazole at a daily dose of 100-150 mg for 198 days without observable adverse reactions.

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Twelve cases of fungal infection were treated with itraconazole (ICZ) at 50200 mg /day for 3155 days.
Clinical assessment revealed improvement in three of four patients with candidal infections, in four of five patients with invasive aspergillosis, and in one of two patients with pulmonary aspergilloma. However, ICZ had no effect on Paecilomyces lilacinus ulcerative keratitis. In one patient with pulmonary aspergilloma, Aspergillus fumigatus was mycologically eradicated and fungal fragments were expectorated during long-term treatment.
The MICs of ICZ against A. fumigatus and P. lilacinus were 0.20.39 and 0.78g/ ml, respectively, as measured by the dilution method. These MICs were markedly low.
The serum concentrations of ICZ and the expectorated amount of ICZ in the sputum were measured by high-performance liquid chromatography. The maximum serum concentration was 412ng/ml 6 hours after oral administration of 100mg and 944ng/m/ 3 hours after oral administration of 200mg. However, the expectorated amount of ICZ in the sputum was low (1, 750ng/ day).
The only side effect was constipation in one patient. ICZ had no effects on the biochemical or hematological parameters. It thus appears to be a valuable tool for treatment of fungal infections, especially aspergillosis.

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We report the case of a 40-year-old man with tinea incognito associated with kerion celsi and tinea barbae. The patient had suffered from tinea pedis for about 10 years. In March of 1989, he developed erythematous itchy plaques on his cheek, which were treated with various topical ointments including corticosteroid at a dermatology clinic without any improvement. On May 23, 1989, he visited our hospital with the development of numerous erythematous plaques with pustules and three nodules on his face.
Physical examination showed nodules and pustules with crusts in the perioral and forehead regions, as well as disseminated erythemas with pustules and scales on his entire face. A fungal infection was confirmed with direct examination of hairs, pustules and scales using KOH preparation. The isolated organisms from those lesions were identified as T. rubrum. The trichophytin reaction was positive. Laboratory studies were within normal ranges except for leukocytosis.
Histopathological findings of nodules from the perioral region revealed marked inflammatory reaction with mainly neutrophils in the dermis and hair follicles. PAS stain showed a number of fungi in the horny layer and hair follicles.
The patient was treated orally with a new antifungal agent, Itraconazole, for 41 days. The organisms could no longer be isolated after 30 days and the lesions disappeared within 40 days of this treatment.

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In the majority of studies on airborne fungal floras in Japan, identification of collected fungal isolates has been limited to the genus level. The exceptions have been the studies on allergens of bronchial asthma and mycotoxin producers. Determination up to the species level was made, however, in a study of airborne fungal floras isolated in the Matsue district of Shimane Prefecture. A high volume air sampler was used to take in air at 7, 200 m³, and 38, 090 airborne fungal colonies were collected in 1975, and 40, 497 colonies in 1989. Identification of the fungi up to the species level was performed throughout the study. Dominant genera in both years were Penicillium, Cladosporium and Aspergillus. The maximum numbers were recorded in the months of November in 1975 and December in 1989. The minimum was seen in June in both years. Penicillium was classified into 26 species, the dominant ones being P. granulatum, P. oxalicum and P. multicolor. All of Cladosporium isolated were determined to be C. cladosporioides Aspergillus. was composed of 9 species, including A. niger, A. flavus and A. fumigatus Fusarium. was represented by 4 species, Paecilomyces by 2, and the others were classified into 34 genera and 28 species. Some representative dominant species of collected fungi were inoculated into soil, where abundant conidia production was commonly detected ; the growth appearance of the fungi on the surface soil was like a mass made up entirely of conidia. Phialides specific to Aspergillus, Penicillium and Paecilomyces were not confirmed in fungi taken from the soil. Thus, the dominant genera of airborne fungi were believed to be highly active in conidia production in surface soil. It was also pointed out that the formation of dominant genera of airborne fungi in the soil was somewhat different from that which appeared in the ordinary test culture.

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Aspergillus species, which are placed in the section Fumigati, were isolated from soil samples of 10 localities in Brazil, Colombia, Paraguay and Venezuela. The isolation was carried out using the soil-plate method, with incubation on Czapek's agar at 37°C for 14 days.
A higher occurrence of Aspergillus species in the sect. Fumigati was generally found in soil samples from the forest. The 18, 750 isolates were identified with A. fumigatus, A. neoellipticus and Aspergillus sp., respectively. A total of 102 isolates of the three species in this section were examined on their proteolytic activity by incubation on Petri plates of brain heart infusion agar with skim milk at 37°C for 8 days. The proteolytic activity was determined by positive sign of casein digestion. Results showed the proteolytic activity on the following : A. fumigatus (33 % positive strains), A. neoellipticus (26%), and Aspergillus sp. (35%).

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In vitro experimental conditions and antifungal activity of terbinafine (SF 86-327), a new all-ylamine antimycotic, were investigated using an agar dilution method. The results are summarized as follows.
1. Experimental conditions influencing MIC values
1) The in vitro antifungal activity of this drug against the most susceptible fungus Trichophyton mentagrophytes was largely independent of medium composition, incubation period, and inoculum size of the fungus.
2) The antifungal activity of this drug was slightly lowered at pH 4, and
3) was clearly decreased by the addition of calf serum to the incubation medium.
2. The in vitro antifungal activity of this drug against a variety of pathogenic fungi was determined in Sabouraud dextrose agar and casitone agar with clotrimazole as a reference drug. The following was shown.
1) Terbinafine had a higher antifungal effectiveness (MIC≤0.04 μg/ml) against most strains of aspergilli and penicillia, various species of chromomycosis-causing fungi, dimorphic fungi, and dermatophytes than did clotrimazole.
2) Terbinafine had the same degree (MIC, 0.31-20 μg/ml) of effectiveness as that of clotrimazole against Candida albicans var. stellatoidea, C. parapsilosis, C. guilliermondii, C. kefyr, and other Candida sp., and Cryptococcus neoformans and other Blastomycetes.
3) C. albicans, C. tropicalis, C. krusei, C. glabrata, and some other Candida spp. were not completely inhibited even at the terbinafine concentration of 80 pg/ml.
4) In a broth culture method, terbinafine inhibited by 90% of the growth at 5 /tem/ ; it was fungicidal sgainst C. parapsilosis at higher concentrations, and also fungicidal to some extent against the germinating conidia of T. mentagrophytes even at low concentrations.

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Therapeutic treatments with 0.252 % cream preparations of terbinafine were carried out to evaluate the topical therapeutic efficacy of terbinafine, a new allylamine antimycotic, in the Trichophyton mentagrophytes-infected guinea pig model, with 1 % bifonazole creams a reference drug.
Therapeutic effectiveness of cream preparations applied once daily from day 5 after infection was checked, based on the degree of symptom and negative detection ratio of infected fungi in semi-quantitative culturing of lesions. The results are summarized as follows.
1) In the group applied terbinafine cream preparations of each concentration, significant improvement of the symptoms was observed after day 7 at latest of treatment, compared with the no-treatment control and vehicle-treatment animal groups. The lesions ceased development on day 4 to day 5, reduced rapidly, and completely disappeared between day 10 to day 14. During this period, however, there was no significant difference in the therapeutic effectiveness between low and high concentrations of the drugs.
2) Culture studies on day 14 showed that, compared with the control counterparts, a significant antifungal therapeutic effectiveness was observed in the treated animal groups with terbinafine cream preparations of any concentration. The negative detection ratio of infected fungi increased dependently with the concentration of terbinafine.
3) Terbinafine preparations exerted a significant therapeutic effectiveness superior to bifonazole preparations in the two above-mentioned measurements in the guinea pig dermatophytosis model.

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An in vitro assay method of anti-Malassezia activity of terbinafine, a new allylamine antimycotic, was examined with clotrimazole as a reference drug using several kinds of media supplemented with different amounts of lipids.
M. furfur did not grow in a lipid-free medium, but grew well in a medium supplemented with glycerol monostearate and Tween 80. Moreover, supplementation of olive oil (0.25 2 %) enhanced the growth of M. furfur. The MIC values of terbinafine against M. furfur greatly depended on the concentration of olive oil added, although the dependency was not limited to Malassezia. On the other hand, M. pachydermatis which does not require lipids for growth proliferated well even in a lipid-free medium, and the MIC values were much smaller than those for M. furfur. Terbinafine's antifungal activity against M. furfur is thus definitely positive and this suggests its therapeutic effectiveness on tinea versicolor.

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