Abstract
The relationship between the azole preexposure of 86 patients and the genotype, azole susceptibility, and cyp51A polymorphisms of 110 corresponding Aspergillus fumigatus isolates was explored. Isolates carrying serial polymorphisms (F46Y and M172V with or without N248T with or without D255E with or without E427K) had higher itraconazole MICs (P = 0.04), although <2 μg/ml using the EUCAST methodology, were associated with two genetic clusters (P < 0.001) and with voriconazole preexposure of patients (P = 0.016). Voriconazole preexposure influences the distribution of A. fumigatus isolates with selection of isolates carrying cyp51A polymorphisms and higher itraconazole MICs.
MeSH terms
-
Antifungal Agents / pharmacology*
-
Aspergillosis / drug therapy*
-
Aspergillosis / microbiology
-
Aspergillus fumigatus / drug effects
-
Aspergillus fumigatus / genetics*
-
Aspergillus fumigatus / isolation & purification
-
Cytochrome P-450 Enzyme System / genetics*
-
Drug Resistance, Fungal / drug effects
-
Drug Resistance, Fungal / genetics
-
Fungal Proteins / genetics*
-
Genotype
-
Humans
-
Itraconazole / pharmacology*
-
Microbial Sensitivity Tests
-
Multigene Family
-
Polymorphism, Single Nucleotide
-
Pyrimidines / pharmacology*
-
Triazoles / pharmacology*
-
Voriconazole
Substances
-
Antifungal Agents
-
Fungal Proteins
-
Pyrimidines
-
Triazoles
-
Itraconazole
-
Cytochrome P-450 Enzyme System
-
cytochrome P-450 CYP51A, Aspergillus
-
Voriconazole