Itraconazole corneofungimetry bioassay on Malassezia species.

Yeasts of the genus Malassezia are part of the normal skin biocenosis and are involved in a series of distinct skin disorders and specific dermatomycoses in man and animals. Several species are currently distinguished. Their relative in vitro susceptibility to antifungals appears different according to the species and to the nature and route of administration of the drug. Corneofungimetry is an ex vivo bioassay allowing to test the fungal response on human stratum corneum following oral intake of a given antifungal by volunteers. Two series of cyanoacrylate skin surface strippings (CSSS) were harvested from the volar forearm of 30 volunteers before and after a 2-week treatment with itraconazole 200 mg daily. They were coated by olive oil and inoculated with suspensions of seven different Malassezia spp. After a 1-week culture on CSSS, the amount of viable yeasts was assessed using neutral red staining assisted by computerized image analysis. Growth of the seven species was not similar on the CSSS from untreated stratum corneum. The ranking order from the most proliferative to the least was M. restricta, M. sympodialis, M. globosa, M. furfur, M. obtusa, M. slooffiae and M. pachydermatis. Their growth was abated to almost the same level after itraconazole treatment. It is concluded that in vivo treatment with itraconazole is highly active against all Malassezia spp. colonizing the human stratum corneum

Activity of the triazole antifungal r126638 as assessed by corneofungimetry.

BACKGROUND: R126638 is a novel triazole exhibiting potent in vitro and in vivo antifungal activity against fungal pathogens including dermatophytes and yeasts. OBJECTIVE: To determine the antifungal activity in time in the stratum corneum of healthy volunteers after oral intake of R126638 at a daily dose of 100 or 200 mg for 1 week. METHOD: Sixteen male volunteers were randomly allocated to oral treatment with either 100 or 200 mg of R126638 once daily for 1 week. Five cyanoacrylate skin surface strippings (CSSS) were obtained from the forearm of each subject before drug intake at day 1. CSSS were also collected during treatment at day 2 (24 h after the first drug intake, before the second drug intake), at day 4 (before the fourth drug intake) and at day 7 (10 h after the last drug intake). The post-treatment lingering effect was assessed at day 10 (3 days after treatment) and at day 14 (7 days after treatment). The corneofungimetry bioassay was performed on these CSSS to assess the antifungal profile of R126638. Cells of different fungal species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Candida albicans and Malassezia globosa) were deposited and cultured for 10 days on CSSS in a sterile and controlled environment. The extent of fungal growth on the stratum corneum was determined using computerized image analysis. RESULTS: R126638 clearly reduced the growth of all tested fungal species. The onset of effects of R126638 was evidenced at day 4 when it reached statistical significance for 3 of 5 species. At day 7, significance was reached for 4 of 5 species. During the posttreatment period, R126638 remained effective for 4 of 5 species at day 10, and this activity persisted until day 14 for 2 of 5 species. CONCLUSION: A broad spectrum antifungal activity was rapidly expressed in the stratum corneum after oral intake of R126638. The drug likely reached the upper layers of the stratum corneum by diffusion and persisted in this location for at least 7 days after treatment