Abstract
Emergence of Aspergillus fumigatus strains containing mutations that lead to azole resistance has become a serious public health threat in many countries. Nucleotide polymorphisms leading to amino acid substitutions in the lanosterol demethylase gene (cyp51A) are associated with reduced susceptibility to azole drugs. The most widely recognized mutation is a lysine to histidine substitution at aa 98 (L98H) and a duplication of the untranscribed promoter region, together known as TR34/L98H. This mechanism of resistance has been reported in Europe, Asia, and the Middle East, and is associated with resistance to all azole drugs and subsequent treatment failures. To determine whether isolates with this mutation are spreading into the United States, we conducted a passive surveillance-based study of 1,026 clinical isolates of A. fumigatus from 22 US states during 2011-2013. No isolates harboring the TR34/L98H mutation were detected, and MICs of itraconazole were generally low.
Highlights
Emergence of Aspergillus fumigatus strains containing mutations that lead to azole resistance has become a serious public health threat in many countries
Characteristics of A. fumigatus Isolates A request for A. fumigatus clinical isolates collected beginning in 2011 was initiated in June 2011
Most A. fumigatus isolates were susceptible to itraconazole
Summary
Emergence of Aspergillus fumigatus strains containing mutations that lead to azole resistance has become a serious public health threat in many countries. A second cyp51A-promoter duplication genotype, the recently discovered TR46/Y121F+T289A, displays high tolerance for voriconazole [13,14] Both genotypes are associated with in vitro MICs that exceed by multiple dilutions the established epidemiologic cutoff value (ECV) of ≤1 μg/ mL published by the European Committee on Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute members for medical azole agents [9,13]. These mutations often contribute to failure of azole therapy in aspergillosis patients [13,14,15,16,17,18,19,20,21,22,23]. Azole-Resistant A. fumigatus, USA, 2011–2013 given the number of aspergillosis cases in this country, its presence could pose a serious public health threat, as it does in Europe
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