title: Passive surveillance for azole-resistant Aspergillus fumigatus, United States, 2011-2013.
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.
authors.forename: Cau D
authors.initials: CD
authors.lastname: Pham
authors.forename: Errol
authors.initials: E
authors.lastname: Reiss
authors.forename: Ferry
authors.initials: F
authors.lastname: Hagen
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
mesh_terms: D019943:Amino Acid Substitution; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000453:epidemiology* / Q000266:history / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics; D001393:Azoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics; D062306:Geography, Medical; D049674:History, 21st Century; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011159:Population Surveillance; D014481:United States / Q000453:epidemiology
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus