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Antimicrobial Agents and Chemotherapy, May 2007, p. 1818-1821, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01217-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vitro Activities of Isavuconazole and Other Antifungal Agents against Candida Bloodstream Isolates{triangledown}

H. Seifert,1* U. Aurbach,1 D. Stefanik,1 and O. Cornely2

Institute for Medical Microbiology, Immunology and Hygiene,1 Department of Internal Medicine, University of Cologne, Cologne, Germany2

Received 27 September 2006/ Returned for modification 22 December 2006/ Accepted 11 February 2007

Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC50s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC50s/MIC90s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.

* Corresponding author. Mailing address: Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Goldenfelsstrasse 19-21, 50935 Cologne, Germany. Phone: 49-221-478-32008. Fax: 49-221-478-32035. E-mail: harald.seifert{at}uni-koeln.de

{triangledown} Published ahead of print on 16 February 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1818-1821, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01217-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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