In Vitro Susceptibilities of CandidaBloodstream Isolates to the New Triazole Antifungal Agents BMS-207147, Sch 56592, and Voriconazole

ABSTRACT BMS-207147, Sch 56592, and voriconazole are three new investigational triazoles with broad-spectrum antifungal activity. The in vitro activities of these three agents were compared with those of itraconazole and fluconazole against 1,300 bloodstream isolates ofCandida species obtained from over 50 different medical centers in the United States. The MICs of all of the antifungal drugs were determined by broth microdilution tests performed according to the National Committee for Clinical Laboratory Standards method using RPMI 1640 as a test medium. BMS-207147, Sch 56592, and voriconazole were all quite active against all Candida sp. isolates (MICs for 90% of the isolates tested [MIC90s], 0.5, 1.0, and 0.5 μg/ml, respectively). Candida albicans was the most susceptible species (MIC90s, 0.03, 0.06, and 0.06 μg/ml, respectively), and C. glabrata was the least susceptible (MIC90s, 4.0, 4.0, and 2.0 μg/ml, respectively). BMS-207147, Sch 56592, and voriconazole were all more active than itraconazole and fluconazole against C. albicans, C. parapsilosis, C. tropicalis, and C. krusei. There existed a clear rank order of in vitro activity of the five azoles examined in this study when they were tested versusC. glabrata: voriconazole > BMS-207147 = Sch 56592 = itraconazole > fluconazole (MIC90s, 2.0, 4.0, 4.0, 4.0, and 64 μg/ml, respectively). For isolates ofCandida spp. with decreased susceptibility to both itraconazole and fluconazole, the MICs of BMS-207147, Sch 56592, and voriconazole were also elevated. These results suggest that BMS-207147, Sch 56592, and voriconazole all possess promising antifungal activity and that further in vitro and in vivo investigations are warranted to establish the clinical value of this improved potency.

[1]  R. Pinner,et al.  The epidemiological features of invasive mycotic infections in the San Francisco Bay area, 1992-1993: results of population-based laboratory active surveillance. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  T. C. White,et al.  Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance , 1998, Clinical Microbiology Reviews.

[3]  D. Bonner,et al.  In Vitro Activity of a New Oral Triazole, BMS-207147 (ER-30346) , 1998, Antimicrobial Agents and Chemotherapy.

[4]  M. Pfaller,et al.  In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates ofCandida spp , 1998, Antimicrobial Agents and Chemotherapy.

[5]  M. Trautmann,et al.  In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection , 1997, Antimicrobial agents and chemotherapy.

[6]  D. Armstrong,et al.  Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis , 1997, Antimicrobial agents and chemotherapy.

[7]  M. Pfaller,et al.  Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae , 1997, Antimicrobial agents and chemotherapy.

[8]  M. Ghannoum,et al.  Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Labora , 1997, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  Steven D. Brown,et al.  In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species , 1996, Antimicrobial agents and chemotherapy.

[10]  J. Perfect,et al.  In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans , 1996, Antimicrobial agents and chemotherapy.

[11]  A. Sugar,et al.  In vitro and in vivo activities of SCH 56592 against Blastomyces dermatitidis , 1996, Antimicrobial agents and chemotherapy.

[12]  E. Bruck,et al.  National Committee for Clinical Laboratory Standards. , 1980, Pediatrics.

[13]  Ellen Jo Baron,et al.  Manual of clinical microbiology , 1975 .