Prevalence,Clinical Relevance, and Azole Resistance of Cryptic Aspergillus Section Fumigati Isolates: A 2000-2013 Survey in a Montreal Hospital

M. Parent-Michaud1, L. de Repentigny1, S. F. Dufresne2

Author address: 

1Univ. of Montreal, Montreal, QC, Canada, 2Maisonneuve-Rosemont Hosp., Montreal, QC, Canada


Cryptic species of Aspergillus section Fumigati are an emerging cause of invasive aspergillosis, and are of growing concern because many isolates display intrinsic in vitro resistance to triazole antifungals, associated with treatment failure. However, the prevalence of these cryptic species can vary widely across institutions, due to varying methods in detection/identification, different patient populations, and differing strategies in antifungal prophylaxis. We therefore conducted a retrospective survey of 1183 stored clinical isolates of Aspergillus fumigatus, collected from 2000 to 2013 at Maisonneuve-Rosemont Hospital. The isolates were cultured on Sabourauddextrose agar, and Czapek-Dox agar, to ascertain their macroscopic and microscopic morphology, and thermotolerance was determined at 49oC. Twenty-one atypical isolates (delayed sporulation and/or no growth at 49oC) were further identified by sequencing of the β- tubulin gene, yielding A. fumigatus (N=9; 9 patients), Aspergillus turcosus (N=4; 4 Pts.), Neosartorya pseudofischeri (N=7; 1 Pt.), and Neosartorya hiratsukae (N=1; 1 Pt.). Antifungal susceptibility to itraconazole, voriconazole and posaconazole was determined using the CLSI M38-A2 broth microdilution procedure. Aspergillus isolates were considered resistant if they showed an MIC above the epidemiological cutoff values (ECVs) for A. fumigatus: >1 μg/ml for itraconazole and voriconazole, and >0.25 μg/ml for posaconazole. All seven N. pseudofischeri isolates were resistant to voriconazole (MIC=4 μg/ml), while the two A. turcosus isolates also showed reduced susceptibility (MIC=2 μg/ml). Cyp51A gene sequencing of these isolates is underway. Review of medical records revealed that all four A. turcosus isolates were associated with airway colonization, that N. hiratsukae caused chronic cavitary aspergillosis, and that N. pseudofischeri was the cause of disseminated pulmonary, nasal sinus and cerebral aspergillosis in an allogeneic hematopoietic stem cell transplant recipient. These findings confirm the overall low prevalence (1%) of cryptic species of Aspergillus section Fumigati among clinical isolates, but also emphasize the need for active surveillance of these emerging resistant species.

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Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)