Isavuconazole susceptibility of Aspergillus and Candida species by EUCAST method.
Antimicrob Agents Chemother. 2013 Aug 19;
Authors: Howard SJ, Lass-Flörl C, Cuenca-Estrella M, Gomez-Lopez A, Arendrup MC
Isavuconazole is a novel second-generation triazole, which has recently been approved by 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 susceptibility 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 multicentre dataset 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 datasets, the following preliminary epidemiological cut-off values (ECOFFs) were suggested; 2 mg/L for Aspergillus fumigatus, Aspergillus terreus and Aspergillus flavus: 4 mg/L for Aspergillus niger, 0.25 mg/L for Aspergillus nidulans and 0.03 mg/L for Candida albicans, Candida parapsilosis and Candida tropicalis. Unfortunately, ECOFFs could not be determined for Candida glabrata or Candida krusei due to an unexplained inter-laboratory MIC variation. For the blinded collection of A. fumigatus isolates all MICs were ≤ 2 mg/L 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 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 official clinical breakpoint setting process.
PMID: 23959309 [PubMed - as supplied by publisher]