Activities of Caspofungin, Itraconazole, Posaconazole, Ravuconazole, Voriconazole, and Amphotericin B against 448 Recent Clinical Isolates of Filamentous Fungi

Abstract

We examined the in vitro activity of caspofungin, posaconazole, voriconazole, ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at <1 g/ml, followed by ravuconazole (91%), voriconazole (90%), and itraconazole (79%). Caspofungin and amphotericin B inhibited 93% and 89% of isolates at <1 g/ml, respectively, with caspofungin demonstrating an MEC 90 of 0.12 g/ml. All three new triazoles and caspofungin inhibited >95% of Aspergillus spp. at <1 g/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at <1 g/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at <0.5 g/ml. The new triazoles and caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.Invasive infections due to Aspergillus spp. and other filamentous fungi have emerged as prominent causes of infectious morbidity and mortality in the United States and worldwide (6,7,20). Treatment of these infections with available antifungal agents still results in an unacceptably high associated mortality (18).Two new antifungal agents recently have been introduced for treatment of invasive aspergillosis or other invasive mold infections. Voriconazole and caspofungin offer new alternatives for therapy of these difficult infections (10, 11). In addition, the investigational triazoles ravuconazole and posaconazole have been demonstrated to have in vitro potency against Aspergillus spp. and selected other filamentous fungi (8,9,24).Since the availability of these agents represents an exciting opportunity for improving the outcome of invasive infections due to filamentous fungi, their in vitro activity against contemporary clinical isolates is of great interest. We performed a 2-year, 20-center survey of filamentous fungal infections from January 2000 through December 2001. We previously reported preliminary results of the activity of new triazoles against molds collected during the first year of this survey (24). We now report final 2-year results, including the in vitro activity of caspofungin, the new triazoles, amphotericin B, and itraconazole against over 400 recent clinical isolates of filamentous fungi collected from January 2000 through December of 2001. In the process, we present the largest collection of clinical mold isolates tested against caspofungin yet reported. MATERIALS AND METHODS Organisms.A total of 448 unique clinical isolates (one per patient, duplicate patient isolates excluded) of filamentous fungi were obtained from 20 different medical centers in the United States and Canada between January 2000 and December 2001. These centers were participants in the SENTRY Antimicrobial Surveillance Program. The isolates were obta...

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