In Vitro Susceptibilities ofMalasseziaSpecies to a New Triazole, Albaconazole (UR-9825), and Other Antifungal Compounds

Abstract

The in vitro activity of the new triazole albaconazole (UR-9825) in comparison with those of flucytosine, fluconazole, ketoconazole, itraconazole, and voriconazole against 70 strains of Malassezia spp. was determined by a microdilution method using a colorimetric indicator for metabolic activity. Albaconazole showed an in vitro profile similar to those of the different antifungals tested (MIC < 0.06 g/ml for all the strains).Yeasts of the genus Malassezia are part of the normal mycota of the skin of humans and other warm-blooded animals, particularly in areas rich in sebaceous glands (19). Malassezia species may also be etiological agents of skin disorders and, uncommonly, systemic infections (3, 6, 16, 24, 30).In 1997, the National Committee for Clinical Laboratory Standards approved a broth micro-and macrodilution method for susceptibility testing of yeasts with RPMI 1640 medium (NCCLS-M27A) (21). However, this document is not applicable to Malassezia species other than Malassezia pachydermatis, because these organisms do not grow without lipidic substances in the medium. Only a few systems for in vitro susceptibility testing of Malassezia species have been described. In addition to present measurements in solid media, several microdilution methods have been used, but the different liquid media used, such as modified Dixon (19,27) and LeemingNotman (15), are turbid; consequently, the visual and turbidimetric results are difficult to interpret. A liquid medium method has been observed to overcome the difficulties in growth reading if one uses a colorimetric indicator for metabolic activity (Alamar blue) (25). Recently, Nakamura et al. (20) described a new microdilution method based on the urease activity of Malassezia spp.Albaconazole (ABC) is a new systemic triazole under development by J. Uriach & Cia S.A. (Barcelona, Spain) with both potent and broad-spectrum antifungal activity, good pharmacokinetics, and excellent bioavailability. It has demonstrated good in vitro activities against pathogenic yeasts (23), dermatophytes (10), and some filamentous fungi (4), including Scedosporium prolificans (5). It has also been shown to be active in the treatment of systemic aspergillosis and candidiasis in experimental animal models (2).The aim of this study was to compare the in vitro activity of ABC with those of five antifungal drugs, namely, flucytosine (5FC), fluconazole (FLC), ketoconazole (KTC), itraconazole (ITC), and voriconazole (VRC), against 70 isolates of Malassezia, namely, M. furfur (n ϭ 24), M. pachydermatis (n ϭ 10), M. sympodialis (n ϭ 21), and M. slooffiae (n ϭ 15). M. furfur was obtained from human skin, that of neonates with long stays in intensive care units. M. pachydermatis and M. slooffiae were obtained from healthy and diseased ears of dogs and pigs, respectively. M. sympodialis was isolated from normal human skin. Susceptibility testing of the drugs was initially performed with M. restricta (n ϭ 1), M. obtusa (n ϭ 1), and M. globosa (n ϭ 24). However, we were unable to obtain MICs due to the ...

Use of Fatty Acid RPMI 1640 Media for Testing Susceptibilities of Eight Malassezia Species to the New Triazole Posaconazole and to Six Established Antifungal Agents by a Modified NCCLS M27-A2 Microdilution Method and Etest

“…Although terbinafine, amorolfine, and established and newer azole compounds have been tested against Malassezia skin isolates by BMD methods (4,12), data on the in vitro performance of amphotericin B are almost exclusively associated with cases of bloodstream infections (1,9,18). However, these studies were performed prior to the resolution of the taxonomic status of Malassezia species and the recognition of new species (5).…”

Antifungal Susceptibility of Malassezia Species Isolated From Pityriasis Versicolor Cases

“…In agreement with other reports, this study also found higher in vitro antifungal activity against all the tested clinical isolates of Malassezia spp, with itraconazole. [8,14,16] In this study fluconazole MICs were significantly higher than those observed for other azole drugs and ranged from ≤ 0.125 µg/mL -16µg/mL for all the isolates in PV cases. This is similar to or lower than those documented in various other studies.…”

“…The ketoconazole MICs range from ≤ 0.03 -8 μg/mL with all the species tested, These values are similar to or higher than those documented in other studies. [14,15,8,17] Garau M et al [8] registered MICs of ≤0.03µg/mL against 70 isolates of Malassezia. Gupta AK et al [15] demonstrated that out of 55 of strains of Malassezia the MIC ranges as ≤ 0.03µg/mL -0.125μg/mL with 95% of them having an MIC of ≤ 0.03μg/mL.…”

“…This is similar to or lower than those documented in various other studies. [15,16,18] The various MIC ranges against fluconazole shown in various studies are ≤ 0.125 -> 64 µg/mL, [16] 0.06 µg/mL -1.0 µg/mL, [18] ≤ 0.5 µg/mL -32 µg/mL, [6] 0.25µg/mL -4 µg/mL, [8] 0.25µg/mL -256 µg/mlL [14] and ≤ 0.125 -> 64µg/mL. Remya et al…”

“…[4] The disease can be cured by using topical antifungal agents like ketoconazole and some patients who do not respond or experience multiple relapses may require systemic antifungal treatment with fluconazole or itraconazole. Hitherto, several methods are available for doing antifungal susceptibility of Malassezia spp in vitro [5][6][7][8][9][10] Only limited data was available on the susceptibility of Malassezia spp against topical imidazole and oral azole derivatives.…”