M-1530. No Evidence of Azole Resistant Fumigati Section Species Strains from Patients Treated for Hematological Malignancies in the Voriconazole Era
Session: Poster Session: Antifungal Susceptibility
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: An increase of invasive aspergillosis (IA) due to azole resistant Aspergillus fumigatus isolates has been reported in the 10 last years. Misidentification by morphotyping with resistant Fumigati section species, such as A. lentulus, or selection of azole resistant isolates due to azole therapies could explain this trend. Therefore, we checked the phenotypic identification of A. fumigatus isolates from hematological patients by using molecular methods and we determined their azole minimal inhibitory concentration (MIC) to itraconazole (ITZ). Methods: Seventy-seven A. fumigatus morphotype isolates were prospectively collected from 51 patients treated for hematological malignancies from January 2006 through December 2007 (3 proven, 32 probable, 1 possible and 15 without IA). Molecular identification was performed by sequencing A. fumigatus β-tubulin gene. ITZ MIC was determined using Etest®. Isolates with ITZ MICs > 4 mg/L were sequenced for up to residue 300 of CYP51A gene and its promoter. Results: All isolates were identified as A. fumigatus upon the sequence of the ß-tubulin gene. Genotyping using 4 microsatellites markers confirmed the heterogeneity of the contaminating/infecting isolates. All but one had ITZ MICs ranged from 0.25 to 2 mg/L, although 30 of 77 isolates had grown from patients treated with voriconazole. Only one isolate had ITZ MIC > 4 mg/L (16 mg/L) whereas voriconazole and posaconazole MIC were < 0.38 mg/L. The patient was not given azole therapy. CYP51A sequencing showed no mutation or tandem repeat insertion in the promoter of the gene. Conclusions: In our hematological population, there is no evidence of emergence of resistant Fumigati section species strains. High ITZ MIC is rare, below 2%.
Alexandre Alanio1, Catherine Cordonnier2, Cécile Pautas2, Cécile Farrugia3, Françoise Foulet3, Françoise Botterel3, Jean Costa3, Martine Liance3, Stéphane Bretagne, MD, PhD4 and  S. Bretagne, None., (1)Mycology Department, Hôpital Henri Mondor, APHP and Université Paris 12, Creteil, France, (2)Hematology Department, Hôpital Henri Mondor, APHP, (3)Mycology Department, Hôpital Henri Mondor, APHP and Université Paris 12, (4)APHP

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