Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus
Correlation between Triazole Treatment History and Susceptibility in Clinically Isolated Aspergillus fumigatus
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DOI：
10.1128/aac.00514-12
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发表时间：
2012-07
影响因子：
4.9
通讯作者：
M. Tashiro;K. Izumikawa;Katsuji Hirano;S. Ide;Tomo Mihara;N. Hosogaya;T. Takazono;Y. Morinaga;Shigeki Nakamura;S. Kurihara;Y. Imamura;T. Miyazaki;T. Nishino;Misuzu Tsukamoto;H. Kakeya;Yoshihiro Yamamoto;K. Yanagihara;A. Yasuoka;T. Tashiro;S. Kohno
中科院分区：
文献类型：
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作者：
M. Tashiro;K. Izumikawa;Katsuji Hirano;S. Ide;Tomo Mihara;N. Hosogaya;T. Takazono;Y. Morinaga;Shigeki Nakamura;S. Kurihara;Y. Imamura;T. Miyazaki;T. Nishino;Misuzu Tsukamoto;H. Kakeya;Yoshihiro Yamamoto;K. Yanagihara;A. Yasuoka;T. Tashiro;S. Kohno
摘要 这是关于 154 株烟曲霉临床分离株的三唑治疗史与三唑 MIC 之间详细关系的第一份报告。伊曲康唑用药持续时间随着伊曲康唑 MIC 的增加而增加，且呈正相关（r = 0.5700，P < 0.0001）。随着伊曲康唑 MIC 的增加，尤其是 MIC 超过 2 μg/ml（0.5 μg/ml 与 2 μg/ml，P = 0.03），伊曲康唑初治分离株的数量急剧减少。我们还研究了伊曲康唑累积使用量与其他唑类药物 MIC 之间的关系。伊曲康唑用药周期与泊沙康唑 MIC 呈正相关（r = 0.5237，P < 0.0001）。随着泊沙康唑 MIC 的增加，伊曲康唑初治菌株的数量也减少，特别是当 MIC 超过 0.5 μg/ml 时（0.25 μg/ml 与 0.5 μg/ml，P = 0.004）。相反，从伊曲康唑使用量和伏立康唑 MIC 散点图获得的相关系数很小（r = -0.2627，P = 0.001）。对三种三唑类药物的敏感性不随伏立康唑暴露时间的变化而变化。此外，我们对从感染唑类烟曲霉的患者中获得的分离株进行了详细分析，包括微卫星基因分型。我们证实，一名慢性肺曲霉病患者在口服伊曲康唑治疗后，由于 cyp51A 基因中的 G54 替换，存在对伊曲康唑和泊沙康唑的获得性耐药。如果长期使用伊曲康唑，我们应该考虑可能出现耐唑类烟曲霉。
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.