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J Antimicrob Chemother ; 74(7): 2047-2050, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31220262

ABSTRACT

BACKGROUND: Fungicide exposure in the environment has driven the emergence of azole-resistant Aspergillus fumigatus worldwide. A screening test allows identification of resistant isolates. OBJECTIVES: We screened clinical samples for azole-resistant Aspergillus through azole-containing agar plates and identified mutations in the cyp51A gene of A. fumigatus. METHODS: Aspergillus isolates from clinical samples collected in a tertiary care centre from 2014 to 2017 were screened for azole resistance. Samples were subcultured in azole-containing agar plates. Isolates with a positive screening test were subject to DNA extraction, DNA amplification and sequencing of the cyp51A gene (coding and promoter regions). Clinical data were obtained from medical records. RESULTS: We screened 43 Aspergillus isolates from 39 patients for azole resistance. Three isolates from three patients grew on azole-containing agar plates: two A. fumigatus and one Aspergillus flavus. PCR analysis and cyp51A sequencing identified the TR34/L98H mutation in both A. fumigatus isolates. The prevalence of cyp51A mutations among A. fumigatus was 8.3% (2/24). Both patients with TR34/L98H mutants were azole naive and presented with invasive aspergillosis; one had multiple myeloma and the other was a liver retransplant recipient. They suffered progressive disease and failed voriconazole therapy. CONCLUSIONS: To the best of our knowledge, this is the first report of azole-resistant A. fumigatus with the TR34/L98H mutation in two azole-naive patients with refractory invasive aspergillosis in Mexico.


Subject(s)
Antifungal Agents/pharmacology , Aspergillosis/epidemiology , Aspergillosis/virology , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/genetics , Azoles/pharmacology , Cytochrome P-450 Enzyme System/genetics , Drug Resistance, Fungal , Fungal Proteins/genetics , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Azoles/therapeutic use , Humans , Mexico/epidemiology , Mutation , Public Health Surveillance
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