期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 57, 期 11, 页码 5426-5431出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01111-13
关键词
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资金
- Astellas Pharma Global Development Inc.
- Astellas Pharma
- bioMerieux
- Gilead Sciences
- Merck Sharp and Dohme
- Pfizer
- Schering Plough
- Soria Melguizo SA
- Ferrer International
- European Union
- ALBAN program
- Spanish Agency for International Cooperation
- Spanish Ministry of Culture and Education
- Spanish Health Research Fund
- Instituto de Salud Carlos III
- Ramon Areces Foundation
- Mutua Madrilena Foundation
- Astellas
- Gilead
- Merck Sharp Dohme
Isavuconazole is a novel expanded-spectrum triazole, which has recently been approved by the FDA as an orphan drug to treat invasive aspergillosis and is currently being studied in phase III clinical trials for invasive candidiasis. The susceptibility of relatively few clinical isolates has been reported. In this study, the isavuconazole susceptibilities of 1,237 Aspergillus and 2,010 Candida geographically diverse clinical isolates were determined by EUCAST methodology at four European mycology laboratories, producing the largest multicenter data set thus far for this compound. In addition, a blinded collection of 30 cyp51A mutant Aspergillus fumigatus clinical isolates and 10 wild-type isolates was tested. From these two data sets, the following preliminary epidemiological cutoff (ECOFF) values were suggested: 2 mg/liter for Aspergillus fumigatus, Aspergillus terreus, and Aspergillus flavus; 4 mg/liter for Aspergillus niger; 0.25 mg/liter for Aspergillus nidulans; and 0.03 mg/liter for Candida albicans, Candida parapsilosis, and Candida tropicalis. Unfortunately, ECOFFs could not be determined for Candida glabrata or Candida krusei due to an unexplained interlaboratory MIC variation. For the blinded collection of A. fumigatus isolates, all MICs were <= 2 mg/liter for wild-type isolates. Differential isavuconazole MICs were observed for triazole-resistant A. fumigatus isolates with different cyp51A alterations: TR34/L98H mutants had elevated isavuconazole MICs, whereas isolates with G54 and M220 alterations had MICs in the wild-type range, suggesting that the efficacy of isavuconazole may not be affected by these alterations. This study will be an aid in interpreting isavuconazole MICs for clinical care and an important step in the future process of setting official clinical breakpoints.
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