TR34/L98H Mutation in CYP51A Gene in Aspergillus fumigatus Clinical Isolates During Posaconazole Prophylaxis: First Case in Korea

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Efficacy of posaconazole against three clinical Aspergillus fumigatus isolates with mutations in the cyp51A gene.

The in vivo efficacy of posaconazole against 4 clinical Aspergillus fumigatus isolates with posaconazole MICs ranging from 0.03 to 16 mg/liter, as determined by CLSI method M38A, was assessed in a nonneutropenic murine model of disseminated aspergillosis. The underlying resistance mechanisms of the isolates included substitutions in the cyp51A gene at codon 220 (M220I), codon 54 (G54W), and cod...

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Rate of cyp51A mutation in Aspergillus fumigatus among lung transplant recipients with targeted prophylaxis.

OBJECTIVES The most common mechanism of azole (itraconazole and voriconazole) resistance in Aspergillus fumigatus is a mutation at the cyp51A locus. The aim of our study was to determine the rate of cyp51A mutations in lung transplant recipients (LTR) undergoing targeted antifungal prophylaxis with 12 weeks of voriconazole. METHODS We conducted a prospective study that included 22 LTR with A....

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Aspergillus fumigatus strains with mutations in the cyp51A gene do not always show phenotypic resistance to itraconazole, voriconazole, or posaconazole.

We performed molecular identification of 98 Aspergillus fumigatus complex isolates with MICs of 1 to 4 μg/ml for itraconazole and searched for the presence of mutations in cyp51A. Most of the isolates (91%) belonged to A. fumigatus sensu stricto. We found 14 different mutations in nine isolates at codons different from G54, M220, G138, G448, and L98. We report new mutations at positions 165, 26...

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cyp51A-based mechanisms of Aspergillus fumigatus azole

72 Since the mid-1990s, a steady increase in the occurrence of itraconazole resistant Aspergillus 73 fumigatus isolates has been observed in clinical contexts leading to therapeutic failure in the 74 treatment of aspergillosis. This increase has been predominantly linked to a single allele of 75 the cyp51A gene, termed ‘TR/L98H’ which is thought to have arisen through the use of 76 agricultural...

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Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China.

Seventy-two A. fumigatus clinical isolates from China were investigated for azole resistance based on mutations of cyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation. To our knowledge, the latter has not been found previousl...

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ژورنال

عنوان ژورنال: Mycopathologia

سال: 2018

ISSN: 0301-486X,1573-0832

DOI: 10.1007/s11046-018-0271-8