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We have compared the activities of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and filamentous fungi. A total of 1,997 clinical isolates of Candida spp., 359 of other yeast species, 697 strains of Aspergillus spp., and 325 nondermatophyte non-Aspergillus spp. were included. The average geometric means of the MICs of agents that were tested against Candida spp. were 0.23 g/ml for amphotericin B, 0.29 g/ml for flucytosine, 0.97 g/ml for fluconazole, 0.07 g/ml for itraconazole, 0.04 g/ml for voriconazole, 0.15 g/ml for caspofungin, and 0.03 g/ml for posaconazole. Voriconazole and posaconazole were active in vitro against the majority of isolates, with resistance to fluconazole and itraconazole, and against Cryptococcus neoformans and other Basidiomycota yeasts. Posaconazole was the most active of antifungal agents tested against Aspergillus spp., with an average geometric mean of 0.10 g/ml. It was active against Paecilomyces spp., Penicillium spp., Scedosporium apiospermum, and some black fungi, such as Alternaria spp. Multiresistant filamentous fungi, such as Scedosporium prolificans, Scopulariopsis brevicaulis, and Fusarium solani, were also resistant to voriconazole, caspofungin, and posaconazole. Amphotericin B and posaconazole were found to be active against most of the Mucorales strains tested. Posaconazole and currently available antifungal agents exhibit a potent activity in vitro against the majority of pathogenic fungal species.Posaconazole is a new triazole agent with an extended spectrum of in vitro activity. It is active against opportunistic, endemic, and dermatophytic fungi (10, 13, 14, 15) as well as Candida, Cryptococcus, and other yeast species (1,3,17,22,23), including isolates that exhibit resistance to fluconazole and itraconazole (3,10,23). It also has a potent activity in vitro against Aspergillus species; posaconazole appears to be more active in vitro against Aspergillus than are amphotericin B, itraconazole, voriconazole, and ravuconazole, inhibiting 95% of isolates at a MIC of Յ1 g/ml (2, 9, 24). In addition, the new triazoles have been shown to have antifungal activity against other species of filamentous fungi, such as Penicillium spp., Paecilomyces spp., and Acremonium spp., and Sporothrix schenckii as well as some isolates of Fusarium spp., Scedosporium apiospermum, and black fungi (9,10,13,18,24,30). Most notably, posaconazole is more active than the other triazole compounds against zygomycetes, with MICs around or below 1 g/ml. Within the class of Zygomycetes, posaconazole appears to be more active against Rhizopus spp. and Absidia corymbifera than against Mucor spp., which is consistent with the prior observation that the zygomycetes appear to be a heterogeneous group with regard to their susceptibilities to antifungal agents (7,9, 16,24,29).We have analyzed the in vitro activity of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and fila...

Six different species were identified. Fusarium solani was the most frequently isolated, followed by Fusarium oxysporum, Fusarium proliferatum and Fusarium verticilloides. Amphotericin B was the only drug with in vitro activity (range: 0.015-32 mg/L). The rest of the antifungals tested (itraconazole, voriconazole, ravuconazole, posaconazole and terbinafine) showed very poor activity against Fusarium, confirming the multiresistant nature of this genus.

We report the in-vitro susceptibility of 27 clinical isolates of Scedosporium apiospermum and 43 of Scedosporium prolificans. S. apiospermum was resistant to fluconazole and flucytosine, with variable susceptibility to amphotericin B, itraconazole, ketoconazole and susceptible to miconazole. Voriconazole was much more active than fluconazole and flucytosine, more active than amphotericin B, itraconazole and ketoconazole and was as active as miconazole against S. apiospermum isolates. Voriconazole and the other six antifungal agents showed low activity against S. prolificans isolates.

The antifungal susceptibility profiles of 77 clinical strains of Mucorales species, identified by internal transcribed spacer sequencing, were analyzed. MICs obtained at 24 and 48 h were compared. Amphotericin B was the most active agent against all isolates, except for Cunninghamella and Apophysomyces isolates. Posaconazole also showed good activity for all species but Cunninghamella bertholletiae. Voriconazole had no activity against any of the fungi tested. Terbinafine showed good activity, except for Rhizopus oryzae, Mucor circinelloides, and Rhizomucor variabilis isolates.

The antifungal susceptibility results for 32 clinical isolates of Scopulariopsis brevicaulis are presented. Flucytosine and itraconazole were inactive in vitro, and MICs of amphotericin B, voriconazole, and terbinafine for all isolates were high, with geometric means of 13, 25.8, and 14.4 g/ml, respectively. Scopulariopsis spp. are common soil saprophytes and have been isolated from a wide variety of substrates (10). They are cosmopolite organisms, and five species have been associated with human diseases: Scopulariopsis brevicaulis, Scopulariopsis brumptii, Scopulariopsis acremonium, Scopulariopsis fusca, and Scopulariopsis koningii. They are dermatomycotic molds and mainly have been associated with onychomycosis (19,20).S. brevicaulis rarely has been reported as a cause of deep fungal infections, but in the last 2 decades a number of severe illnesses have been documented in hosts presenting factors which predispose them to infection. The spectrum of severe human mycoses includes the formation of fungus balls in preformed pulmonary cavities (6), keratitis (11), posttraumatic endophthalmitis (7), disseminated skin lesions in AIDS patients (5), granulomatous subcutaneous infections (3), invasive hyalohyphomycosis (17, 18), pneumonia in leukemic patients (21), endocarditis related to valvuloplasty or prosthetic valves (8,12,14), and fatal disseminated infection after bone marrow transplantation (13, 16). In addition some isolates of S. brevicaulis have been demonstrated to be pathogenic in murine models of disseminated infection (10).Optimal treatment of these fungal infections is unknown. Debridement or excision of necrotic tissue and antifungal chemotherapy should be the treatments of choice (18). But indications for surgery are limited, and the dose and duration of chemotherapy are not established. Prognosis depends mainly on the patient's immune status and feasibility of surgical debridement (13). Moreover, several authors have suggested that S. brevicaulis is resistant in vitro to amphotericin B, flucytosine, and azole compounds (2, 9).This study describes the susceptibility in vitro to broadspectrum antifungal agents of clinical isolates of S. brevicaulis.(This work was presented in part at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Calif., 2002.) Fungi. A collection of 32 clinical isolates was included. All strains were recovered during a period of 3 years (2000 to 2002) from 17 Spanish hospitals. Each clinical isolate represented a unique isolate from a patient. Paecilomyces variotii (ATCC 22319) and Aspergillus fumigatus (ATCC 9197) were used as reference strains to control the quality and to monitor the reproducibility of susceptibility tests.The isolates were sent to the Mycology Unit for antifungal susceptibility testing with a referral note including both clinical and microbiological data. All strains were isolated from nail or skin scrapings. A total of 25 of 32 (78.1%) isolates were associated with onychomycosis. There was not history of antifungal treatm...

In vitro susceptibility profiles of 58 Paecilomyces clinical isolates are reported. Amphotericin B, itraconazole, and echinocandins showed poor activity against Paecilomyces lilacinus, while the new triazoles were active against it. Paecilomyces variotii exhibited a different susceptibility pattern, being susceptible to most antifungal agents apart from voriconazole and ravuconazole.Paecilomyces species are saprophytic filamentous fungi that are found worldwide in soil and as air and water contaminants (9, 13). Among species in this genus, Paecilomyces lilacinus and Paecilomyces variotii are of clinical importance, as they are an increasing cause for opportunistic and usually severe human infections (2, 4, 5, 15) generally associated with the use of immunosuppression therapy, implants, or ocular surgery.The differentiation between these two species is clinically important, since P. lilacinus and P. variotii seem to present marked differences in their in vitro susceptibilities to the antifungal agents. We report here the in vitro susceptibility profile of a collection of P. variotii and P. lilacinus clinical isolates.Strains. This study included 58 clinical isolates of Paecilomyces spp. obtained from a variety of clinical sources.Morphological identification. The strains were subcultured at 30°C in malt extract agar (2% malt extract) (Oxoid S.A., Madrid, Spain) and potato dextrose agar (Oxoid) to ascertain their macroscopic and microscopic morphologies.Molecular identification by sequencing of internal transcribed spacer (ITS) region. Molds were cultured in GYEP medium (0.3% yeast extract, 1% peptone) (Difco, Soria Melguizo S.A., Madrid, Spain) with 2% glucose (Sigma-Aldrich Quimica, Madrid, Spain) for 24 to 48 h at 30°C. Genomic DNA was isolated using an extraction procedure previously described (10).DNA segments comprising the ITS1 and ITS2 regions were amplified with primers ITS1 (5Ј-TCCGTAGGTGAACCTGC GG-3Ј) and ITS4 (5Ј-TCCTCCGCTTATTGATATGC-

Two different methods of inoculum preparation for susceptibility testing were analysed. The first method was adjustment of inoculum size by haemocytometer counting. The second method was spectrophotometric adjustment at 530 nm. The reliability of both methods was assessed by colony counting. The overall agreement between colony counting and haemocytometer counts was 93.6%, and the intraclass coefficient correlation was 0.71 (P < 0.05). Pearson's correlation index between colony counts and optical density values was -0.059 (P > 0.05). Optical densities ranged between 0.01 and 1.2, showing less reproducibility than expected by the NCCLS M 38-P standard. Haemocytometer counting is a more reliable method of inoculum preparation for antifungal susceptibility testing.