In humans, Scopulariopsis is mainly associated with onychomycoses, rarely with cutaneous infections or with invasive mycoses. However, during the last two decades, deep infections caused by members of this genus have been increasing. Scopulariopsis brevicaulis is the most common species described as an etiologic agent of human disease. Previous antifungal susceptibility studies indicate that this species is resistant in vitro to the broad-spectrum antifungal agents that are available today. Here, we describe the antifungal activity of amphotericin B, terbinafine, ciclopirox, itraconazole, ketoconazole, and voriconazole against 40 S. brevicaulis isolates. Antifungal susceptibility tests were performed using a modified Clinical and Laboratory Standards Institute M38-A2 procedure. The results showed that itraconazole had the highest minimal inhibitory concentration (MIC) of >16 mg/l; amphotericin B, voriconazole, and ketoconazole MICs were ranging from 4 to >16 mg/l, 8 to >16 mg/l, and 8 to >16 mg/l, respectively; and the best activity was found with terbinafine and ciclopirox with MICs ranging from 0.5 to 16 mg/l and 1 to 8 mg/l, respectively.
The in vitro activities of 11 antifungal drugs against 68 Scopulariopsis and Microascus strains were investigated. Amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole, miconazole, posaconazole, voriconazole, and ciclopirox showed no or poor antifungal effect. The best activities were exhibited by terbinafine and caspofungin, where the MIC and MEC (minimal effective concentration) ranges were 0.0313 to >16 g/ml and 0.125 to 16 g/ml, respectively. The MIC and MEC modes were both 1 g/ml for terbinafine and caspofungin; the MIC 50 and MEC 50 were 1 g/ml for both drugs, whereas the MIC 90 and MEC 90 were 4 g/ml and 16 g/ml, respectively. The genera Scopulariopsis and Microascus include opportunistic fungal pathogens of humans. Taxonomically, they belong to the family Microascaceae within the class Sordariomycetes (Ascomycota). Scopulariopsis species are best known as the causative agents of onychomycoses, i.e., less common skin, subcutaneous, and deep tissue infections. They have been implicated in, for example, keratitis (1), sinusitis (2), bronchitis (3), endocarditis (4), meningitis (5), pulmonary infection (6), and disseminated mycoses (7). Infections due to Microascus species are locally invasive, involving organs such as the lungs (8), brain (9), and endocardium (10), or disseminated (11). The prognosis in invasive infections is poor, and many of the reported cases have ended in death. Therapeutic difficulties have been associated with patients' underlying disease, lack of clear guidelines for treatment, and resistance of the fungi to antimycotics (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Data on the in vitro antifungal susceptibility of Scopulariopsis and Microascus are scant and relate almost exclusively to Scopulariopsis brevicaulis, which has been clinically the most frequently isolated species. Most of these studies have indicated that S. brevicaulis exhibited a multidrug-resistant phenotype (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). To the best of our knowledge, there have been only three published studies reporting on drug susceptibility results also for other than S. brevicaulis species (12,13,21). The purpose of this study was to evaluate the in vitro activities of 11 antifungal drugs against various Scopulariopsis and Microascus species, including rare species, which were not tested before.A total of 68 fungal strains were evaluated: 23 Microascus and 45 Scopulariopsis strains, representing 10 and 16 species, respectively. All strains were purchased from the Centraalbureau voor Schimmelcultures (CBS) culture collection (Utrecht, The Netherlands). The list of strains tested is presented in Table S1 in the supplemental material. Fungal inocula were prepared from 14-day-old cultures in Czapek yeast agar using the method described previously (20). The following antifungal drugs were used in the study: 5-fluorocytosine (5FC), amphotericin B (AMB), caspofungin (CFG), ciclopirox (CPX), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), miconazole (MCZ), posaconazole (POS)...
The genus Scopulariopsis contains over 30 species of mitosporic moulds, which although usually saprophytic may also act as opportunistic pathogens in humans. They have mainly been associated with onychomycosis, and only sporadically reported as a cause of deep tissue infections or systemic disease. Identification of Scopulariopsis species still largely relies on phenotype-based methods. There is a need for a molecular diagnostic approach, that would allow to reliably discriminate between different Scopulariopsis species. The aim of this study was to apply sequence analysis of partial 28S rRNA gene for species identification of Scopulariopsis clinical isolates. Although the method employed did reveal some genetic polymorphism among Scopulariopsis isolates tested, it was not enough for species delineation. For this to be achieved, other genetic loci, within and beyond the rDNA operon, need to be investigated.
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