title: Correlation between triazole treatment history and susceptibility in clinically isolated Aspergillus fumigatus.
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.
authors: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Masato
authors: M
authors: Tashiro
authors: Koichi
authors: K
authors: Izumikawa
authors: Katsuji
authors: K
authors: Hirano
authors: Shotaro
authors: S
authors: Ide
authors: Tomo
authors: T
authors: Mihara
authors: Naoki
authors: N
authors: Hosogaya
authors: Takahiro
authors: T
authors: Takazono
authors: Yoshitomo
authors: Y
authors: Morinaga
authors: Shigeki
authors: S
authors: Nakamura
authors: Shintaro
authors: S
authors: Kurihara
authors: Yoshifumi
authors: Y
authors: Imamura
authors: Taiga
authors: T
authors: Miyazaki
authors: Tomoya
authors: T
authors: Nishino
authors: Misuzu
authors: M
authors: Tsukamoto
authors: Hiroshi
authors: H
authors: Kakeya
authors: Yoshihiro
authors: Y
authors: Yamamoto
authors: Katsunori
authors: K
authors: Yanagihara
authors: Akira
authors: A
authors: Yasuoka
authors: Takayoshi
authors: T
authors: Tashiro
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D025141:Drug Resistance, Fungal / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D055732:Pulmonary Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus