Antifungal Susceptibilities of the Species of the Pseudallescheria boydii Complex

Abstract

Eighty-four isolates belonging to eight species that constitute the Pseudallescheria boydii complex were tested against 11 antifungal agents by using the microdilution method. There were significant differences among the species, with Scedosporium aurantiacum being the most resistant. In general, voriconazole was the most active drug, followed by posaconazole.In the last few decades, Pseudallescheria boydii sensu lato has been emerging as an important human pathogen, particularly in immunocompromised hosts (8). The optimal treatment for these infections is unknown, and the mortality rate is very high despite aggressive antifungal treatment (8). It has been repeatedly demonstrated that P. boydii sensu lato has low in vitro (6) and in vivo (3, 4, 9) susceptibilities to traditional antifungal drugs. However, the new triazoles, such as voriconazole (VRC), ravuconazole (RVC), and posaconazole (PSC), have shown some in vitro activities against this fungus (5). VRC has also shown efficacy both in animal models (3, 4) and in the clinical setting (1, 13). However, not all the strains of P. boydii tested responded equally to VRC. For instance, Capilla and Guarro (3) demonstrated that one strain that showed a VRC MIC of 0.5 to 1 g/ml was susceptible to this drug in a guinea pig model, while another strain with a VRC MIC of 8 g/ml was resistant. Similarly, some human infections have responded to treatment with this drug (1) and others have not (15). This could be explained by the fact that P. boydii does not represent a single species but instead is a complex comprising at least six known species (P. boydii, Pseudallescheria angusta, Pseudallescheria ellipsoidea, Pseudallescheria fusoidea, Pseudallescheria minutispora, and Scedosporium aurantiacum) and two cryptic species represented by clades 3 and 4 as described by Gilgado et al. (7). Since the antifungal susceptibilities of these species are unknown, we have evaluated the in vitro activities of 11 drugs against strains representing all of them.Eighty-four isolates were tested (Table 1). The isolates were stored in slant cultures of potato dextrose agar (Difco Laboratories, Detroit, Mich.) covered with paraffin oil, subcultured on potato dextrose agar plates, and incubated at 30°C for 5 to 6 days. Candida krusei ATCC 6258 and Candida parapsilosis ATCC 22019 were included as quality controls. Antifungal agents were obtained as pure powders. Amphotericin B (AMB) (USP, Rockville, MD), itraconazole (ITC) and ketoconazole (KTC) (Janssen Pharmaceutica, Beerse, Belgium), albaconazole (J. Uriach & Cía, Barcelona, Spain), VRC (Pfizer Inc., Madrid, Spain), PSC (Schering-Plough Ltd., Hertfordshire, United Kingdom), RVC (Bristol-Myers Squibb Company, New Brunswick, NJ), and terbinafine (Novartis, Basel, Switzerland) were diluted in dimethyl sulfoxide (Panreac Química S.A., Barcelona, Spain), and micafungin (MFG) (Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan), flucytosine (5FC) (Sigma-Aldrich Corp., St. Louis, MO), and fluconazole (FLC) (Pfizer Inc., Madrid, Spain) were diluted in s...

Molecular Typing of AustralianScedosporiumIsolates Showing Genetic Variability and NumerousS. aurantiacum

“…Since scedosporiosis, in particular that caused by S. prolifi cans, is often refractory to treatment (3,5), preventive strategies are of paramount importance. However, the epidemiology and mode of transmission of infection are not well understood.…”

“…In contrast to the well-documented opportunists Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, the epidemiology and evolution of human infections caused by uncommon but emerging fungi are incompletely understood. Such pathogens include Scedosporium apiospermum (teleomorph Pseudallescheria boydii) and S. prolifi cans, which are inherently resistant to many antifungal agents (3)(4)(5).…”

Pseudallescheria fusoidea , a New Cause of Osteomyelitis

“…Diagnosis by histopathology alone may not be sufficient, since some of these fungi may have similar morphological characteristics but vary greatly in their drug sensitivities. For example, species of the genus Aspergillus are typically susceptible to antifungal drugs such as itraconazole and amphotericin B (15), while Pseudallescheria boydii, which can be difficult to differentiate from Aspergillus histopathologically, is resistant to these drugs (9). The P. fusoidea isolate described in this report displayed high MICs to many of the commonly used antifungal agents including amphotericin B, fluconazole, and itraconazole.…”

“…However, as in the current case, the discriminatory power of the rDNA gene sequence was not great enough to distinguish between species of this genus. The use of an additional gene sequence, the ␤-tubulin gene in this case, was necessary to determine the final identification (7,9). The TUB region of the ␤-tubulin gene has been shown to be the most informative in the phylogenic analysis of P. boydii and its relatives, as demonstrated in a previous multilocus sequence study (7).…”

Scedosporiosis in patients with acute leukemia: a retrospective multicenter report

“…At present, the new triazoles, voriconazole and posaconazole, as well as a combined treatment should be considered as a possible option to modify outcome. 41,[44][45] Even though the antifungal drugs registered for empiric therapy (AmB formulations and caspofungin) are not intrinsically active against Scedosporium spp, the very low incidence of scedosporiosis also in AML patients does not justify the use of other antifungal drugs active against these highly pathogenic fungi in the empiric setting.…”