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Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus


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Title: Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus
Authors: Tashiro, Masato / Izumikawa, Koichi / Hirano, Katsuji / Ide, Shotaro / Mihara, Tomo / Hosogaya, Naoki / Takazono, Takahiro / Morinaga, Yoshitomo / Nakamura, Shigeki / Kurihara, Shintaro / Imamura, Yoshifumi / Miyazaki, Taiga / Nishino, Tomoya / Tsukamoto, Misuzu / Kakeya, Hiroshi / Yamamoto, Yoshihiro / Yanagihara, Katsunori / Yasuoka, Akira / Tashiro, Takayoshi / Kohno, Shigeru
Issue Date: Sep-2012
Publisher: American Society for Microbiology
Citation: Antimicrobial Agents and Chemotherapy, 56(9), pp.4870-4875; 2012
Abstract: This is the first report of a detailed relationship between triazole treatment history and triazole MICs for 154 Aspergillus fumigatus clinical isolates. The duration of itraconazole dosage increased as the itraconazole MIC increased, and a positive correlation was observed (r = 0.5700, P < 0.0001). The number of itraconazole-naïve isolates dramatically decreased as the itraconazole MIC increased, particularly for MICs exceeding 2 μg/ml (0.5 μg/ml versus 2 μg/ml, P = 0.03). We also examined the relationship between cumulative itraconazole usage and the MICs of other azoles. A positive correlation existed between itraconazole dosage period and posaconazole MIC (r = 0.5237, P < 0.0001). The number of itraconazole-naïve isolates also decreased as the posaconazole MIC increased, particularly for MICs exceeding 0.5 μg/ml (0.25 μg/ml versus 0.5 μg/ml, P = 0.004). Conversely, the correlation coefficient obtained from the scattergram of itraconazole usage and voriconazole MICs was small (r = -0.2627, P = 0.001). Susceptibility to three triazole agents did not change as the duration of voriconazole exposure changed. In addition, we carried out detailed analysis, including microsatellite genotyping, for isolates obtained from patients infected with azole-resistant A. fumigatus. We confirmed the presence of acquired resistance to itraconazole and posaconazole due to a G54 substitution in the cyp51A gene for a patient with chronic pulmonary aspergillosis after oral itraconazole therapy. We should consider the possible appearance of azole-resistant A. fumigatus if itraconazole is used for extended periods.
Keywords: Aspergillus fumigatus / MIC / azole / resistance
URI: http://hdl.handle.net/10069/30252
ISSN: 00664804
DOI: 10.1128/AAC.00514-12
Rights: © 2012, American Society for Microbiology. All Rights Reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/30252

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