Azole preexposure affects the Aspergillus fumigatus population in patients

Alexandre Alanio (1, 2) , Odile Cabaret (2) , Emilie Sitterlé (2) , Jean-Marc Costa (2) , Sylvain Brisse (3) , Catherine Cordonnier (4) , Stephane Bretagne (2, 1)

1 Mycologie moléculaire
2 Laboratoire de parasitologie mycologie
3 PF8 - Génotypage des Pathogènes et Santé Publique (Plate-forme)
4 Service d'hématologie clinique

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 \textless2 μg/ml using the EUCAST methodology, were associated with two genetic clusters (P \textless 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.

Keywords: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Cytochrome P-450 Enzyme System; Drug Resistance; Fungal; Fungal Proteins; Genotype; Humans; Itraconazole; Microbial Sensitivity Tests; Multigene Family; Polymorphism; Single Nucleotide; Pyrimidines; Triazoles; voriconazole

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology; Mycology

Alexandre Alanio, Odile Cabaret, Emilie Sitterlé, Jean-Marc Costa, Sylvain Brisse, et al.. Azole preexposure affects the Aspergillus fumigatus population in patients. Antimicrobial Agents and Chemotherapy, 2012, 56 (9), pp.4948--4950. ⟨10.1128/AAC.05990-11⟩. ⟨pasteur-01405250⟩