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Emergence ofAspergillus fumigatusazole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

Authors: Dauchy, C.; Bautin, N.; Nseir, S.; Reboux, G.; Wintjens, R.; Rouzic, O. Le; Sendid, B.; +6 Authors

Emergence ofAspergillus fumigatusazole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes

Abstract

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.

Keywords

Drug Resistance, Fungal -- genetics, Azoles, Male, Antifungal Agents, MESH: Fungal Proteins/isolation & purification, [SDV]Life Sciences [q-bio], Colony Count, Drug Resistance, Colony Count, Microbial, MESH: Aspergillus fumigatus/drug effects, MESH: Cytochrome P-450 Enzyme System/drug effects, MESH: Genotype, Pulmonary Disease, Chronic Obstructive, Microbial, dwelling, Cytochrome P-450 Enzyme System, Pulmonary Disease, Chronic Obstructive -- microbiology, Prevalence, Prospective Studies, MESH: Aged, Fungal/genetics, MESH: Middle Aged, Azole-resistance, Mold environmental exposure, Sciences bio-médicales et agricoles, Middle Aged, MESH: Housing, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Air Pollution, Indoor, Acute Disease, MESH: Drug Resistance, Disease Progression, Fungal -- genetics, MESH: Acute Disease, Indoor -- analysis, MESH: Cytochrome P-450 Enzyme System/isolation & purification, MESH: Disease Progression, Female, MESH: Air Pollution, Chronic Obstructive -- microbiology, Genotype, MESH: Fungal Proteins/drug effects, MESH: Pulmonary Disease, 610, Aspergillus fumigatus -- drug effects -- genetics -- isolation & purification, MESH: Azoles/pharmacology*, Fungal Proteins -- drug effects -- isolation & purification, chronic obstructive pulmonary disease, Pulmonary Disease, Fungal Proteins, azole resistance, Aspergillus fumigatus; mold environmental exposure; azole resistance; chronic obstructive pulmonary disease; dwelling; electrostatic dust collector, Drug Resistance, Fungal, Air Pollution, 616, COPD, Humans, MESH: Aspergillus fumigatus/genetics, Dwelling, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Prevalence, Aged, MESH: Humans, Indoor/analysis*, Aspergillus fumigatus, Azoles -- pharmacology, electrostatic dust collector, mold environmental exposure, Chronic Obstructive/microbiology*, Electrostatic dust collector, MESH: Colony Count, MESH: Male, MESH: Prospective Studies, Cytochrome P-450 Enzyme System -- drug effects -- isolation & purification, Housing, MESH: Aspergillus fumigatus/isolation & purification*, MESH: Female, MESH: Antifungal Agents/pharmacology*, Antifungal Agents -- pharmacology, Air Pollution, Indoor -- analysis

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
37
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25
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