In Vitro Activities of Ravuconazole (BMS-207147) against 541 Clinical Isolates of Cryptococcus neoformans

Abstract

The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (MIC at which 90% of the isolates are inhibited [MIC 90 ], 0.25 g/ml) was more active than either itraconazole (MIC 90 , 0.5 g/ml) or fluconazole (MIC 90 , 8 g/ml). Among the isolates inhibited by >16 g of fluconazole/ml, 90.2% were inhibited by <1 g of ravuconazole/ml. On the basis of our findings and the favorable pharmacokinetic properties of ravuconazole, we suggest that ravuconazole may be useful for the treatment of infectious diseases due to C. neoformans and that further clinical studies to confirm these promising in vitro results are warranted.Cryptococcus neoformans has a worldwide distribution and is one of the most important agents of life-threatening infection among the community-acquired opportunistic fungal pathogens (4). Since the 1980s the incidence of Cryptococcus infections in some countries has increased dramatically as a result of AIDS (4, 7). In the United States, the majority of studies report a prevalence of C. neoformans infection among human immunodeficiency virus (HIV)-infected patients in the 5 to 10% range (4, 11). For the treatment of cryptococcal meningitis, fluconazole has been primarily used for maintenance therapy or prophylaxis (15). However, concerns regarding fluconazole-resistant strains of C. neoformans have been expressed by several investigators (2, 3). Itraconazole has been found to be less effective than fluconazole in the treatment of cryptococcal meningitis in HIV-infected patients (17). For these reasons, investigation of the activities of newer antifungal agents against C. neoformans is desired.Ravuconazole (BMS-207147) is a novel triazole antifungal agent (1, 18) with a broad antifungal spectrum and potent activities against major pathogenic fungi such as Aspergillus fumigatus, C. neoformans, Candida spp., and dermatophytes (5,6,8,9). Although its activity against C. neoformans is promising, earlier investigations included limited numbers of clinical isolates, and there is a lack of comparative data with other azole agents. This study provides comparative in vitro susceptibility data for three triazole antifungal agents against a large number of clinical isolates of C. neoformans.A total of 541 clinical isolates of C. neoformans from geographically diverse locations were selected for this study. The collection included 396 isolates from cerebrospinal fluid cultures, 116 from blood cultures, and 29 from miscellaneous clinical specimens (pleural fluid, urine, etc.). All isolates were stored as suspensions in sterile distilled water at room temperature until the study was performed. Prior to testing, each isolate was subcultured at least twice on potato dextrose agar plates (Remel, Lenexa, Kans.) to ensure purity and optimal growth.Standard antifungal pow...

In Vitro Antifungal Susceptibility of Cryptococcus gattii

“…In general, ABC and RVC were the most active drugs tested. VRC also showed good in vitro activity, as has been reported by other authors (21,23). In this study, we have compared the antifungal susceptibilities of clinical and environmental isolates.…”

“…Despite these differences, only C. neoformans has been included in the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) (13) for testing yeast. Some studies on the in vitro antifungal susceptibility of C. neoformans have been performed (11,16,21), but scarce data exist on the other species. Only a few strains of C. gattii have been tested up to now.…”

Evaluation of Etest Method for Determining Voriconazole and Amphotericin B MICs for 162 Clinical Isolates of Cryptococcus neoformans

“…These isolates were all recent clinical isolates from 50 geographically diverse medical centers worldwide. The C. neoformans organisms had all been isolated from either cerebrospinal fluid or blood samples from infected patients (14,24). All isolates were stored as suspensions in sterile distilled water at room temperature until used in the study.…”

Global Trends in the Antifungal Susceptibility of Cryptococcus neoformans (1990 to 2004)

“…At the University of Iowa, we have conducted surveillance of cryptococcosis (i.e., meningitis and cryptococcemia) using a consistent protocol (consecutive incident isolates, one per patient, multiple institutions) and standardized reference quality identification and antifungal susceptibility testing methods from 1990 up to the present (25,37,38,47). This cumulative experience allows us to examine change in the in vitro suscep-tibility of C. neoformans to commonly used antifungal agents (amphotericin B, flucytosine, fluconazole) spanning a 15-year period and representing 100 medical centers in five geographic regions throughout the world.…”