Azole preexposure affects the Aspergillus fumigatus population in patients.
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.
Institut Pasteur, Unité de mycologie moléculaire, Paris, France.
Alexandre
A
Alanio
Odile
O
Cabaret
Emilie
E
Sitterlé
Jean-Marc
JM
Costa
Sylvain
S
Brisse
Catherine
C
Cordonnier
Stéphane
S
Bretagne
D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000187:drug effects / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D020641:Polymorphism, Single Nucleotide; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D005656:Fungal Proteins; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole