Comprehensive information on the action mechanism of one of major imidazole antimycotics, econazole, is treated in this review. Physiological, biochemical and morphological studies so far carried out in our laboratory and others provide evidence that the primary site of antifungal action of econazole, as well as that of other imidazole derivatives, is on the cell membrane of sensitive fungi. Experimental findings obtained from studies with liposomes of various lipid composition show that econazole and other imidazoles selectively interact with phospholipids, particularly those with unsaturated or short-chain acyl groups, resulting in an increase of membrane fluidity. This can be reasonably interpreted as the molecular basis for disintegration of the fungal cell membrane induced by these imidazole compounds. Normal structural and transport and permeability characteristics of the membrane are altered to the extent that the fungal cells cannot maintain the adequate levels of essential ions and metabolites, and the internal milieu of the cells becomes significantly unfavorable, ultimately leading to fungistasis or cell death. Econazole and other imidazoles are also demonstrated to inhibit some enzymatic steps in the pathway of synthesis of ergosterol, an integral sterol component of fungal cell membrane. However, it still remains to be answered how this inhibition would contribute to the membrane disorganization, warranting further investigation. Although all imidazole antimycotics appear to share the common mechanism of action in these aspects, the intensity of the action of econazole on the fungal cell membrane or phospholipid model membranes is similar to that of other members of phenethyl imidazole derivatives, like miconazole, and much greater than that of a trithyl imidazole derivative clotrimazole, when compared on the molar basis.

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Following are the statistical observations of dermatophytoses at the Dermatology clinic in Kobe Central Municipal Hospital from January 1972 to December 1980. Of 4357 specimens from the patients with dermatophytoses, 2949 (67.7%) was positive for dermatophytes. The dermatophytes most frequently isolated was Trichophyton rubrum 76.6%, followed by T. mentagrophytes 19.2%, Microsporum canis 1.9%, Epidermophyton floccosum 1.7%, T. violaceum 0.3% and M. gypseum 0.3%. Clinically Tinea pedis was most common, followed by Tinea cruris, Tinea corporis, Tinea manuum and Tinea unguium, and Trichophyton rubrum was isolated in 66.0-97.0% as their causative dermatophytes. On the other hand, Kerion celsi, Tinea capitis, Sycosis parasitaria, Tinea superficialis universalis and granulomatous lesions of glaburous skin were uncommon. In recent years, Microsporum canis has the tendency to increase, it was isolated from Tinea capitis 85.7%, Kerion celsi 53.8%, Tinea superficialis universalis 50.0% and granulomatous lesions of glaburous skin 14.3%. From Sycosis parasitaria, Trichophyton rubrum 100.0% was isolated. Our statistics were similar to that of the other clinics in Kinki districts.

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The effects of a glycoprotein toxin (Fr II-2) derived from Candida albicans on in vitro and in vivo transformation of rabbit peripheral lymphocytes were described. The addition of Fr II-2 into the whole blood cultivation method system resulted in the marked inhibition of lymphocyte transformation by PHA and Con A. The change of the inhibitory activity was traced at intervals of addition of the toxin and Candida mannan. The toxin inhibited in the same grade at each interval, whereas mannan did not inhibit when added after stimulation with those mitogens. When formol-killed and living cells of C. albicans were intravenously injected into rabbits, peripheral lymphocytes were decreased in population, and their responsiveness to mitogens. These results suggest that glycoprotein toxins would play an important part in impairment of host defense mechanisms involving cellular immunity by C. albicans infection.

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The following observations have been made about each species of Pityrosporum: P. orbiculare, P. ovale, P. pachydermatis and Pityrosporum sp. 1) Among species tested, P. ovale, P. pachydermatis and Pityrosporum sp. utilized asparagine, glutamic acid and ornithine. 2) P. orbiculare, P. pachydermatis and Pityrosporum sp. required nicotinic acid as growth factor. 3) The growth of P. ovale and Pityrosporum sp. was stimulated strongly by oleic acid. 4) The growth of P. orbiculare was stimulated strongly by 7.5% of sodium lactate and this organism could grow in the concentration above 10% of the acid, whereas other species did not. 5) By ouchterlony gel diffusion test, common and species specific antigens were detected. These biochemical and serological characteristics may contribute to the characterization of each species of Pityrosporum.

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A 29 year old patient with onychomycosis due to Microsporum gypseum, which affected the right index fignger nail, was reported. The proximal part of the affected nail was discoloured, deformed and partially destroyed with surrounding erythematous reaction. KOH preparation of nail materials showed numerous hyphae and Microsporum gypseum was isolated as the causative fungus. The strain successfully mated with Nannizzia gypsea “-” (IMI 86176) on soil and hair medium. The lesion was cured without recurrence by oral administration of griseofulvin 500mg daily for 4 months. Source of the infection was not determined.

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A 14-year-old girl with chronic mucocutaneous candidiasis, who had failed to improve on conventional therapy, showed a notable clinical response to oral ketoconazole. The thrush completely cleared within three days. Candida onychia cleared slowly during six months of treatment. There was no adverse drug effect in this patient. Ketoconazole seems to be an effective antifungal agent for chronic mucocutaneous candidiasis, even in the setting of deficiency in cell mediated immunity.

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