title: Multi-triazole-resistant Aspergillus fumigatus infections in Australia.
abstract: The emergence of triazole resistance, including multi-triazole-resistant Aspergillus fumigatus is being reported around the world, but there has been little evidence of this problem to date in Australia. Here we describe a retrospective search of antifungal susceptibility results of all Australian clinical A. fumigatus isolates referred to the National Mycology Reference Centre, Adelaide, Australia between 2000 and 2013, yielding 13 isolates with elevated minimum inhibitory concentrations to itraconazole, posaconazole and/or voriconazole. Four isolates were found to be Aspergillus lentulus, a closely related, morphologically similar species known to have reduced susceptibility to triazoles. Analysis of the cyp51A gene of nine confirmed A. fumigatus isolates revealed two carrying the TR34 /L98H mutation, one apparently locally acquired in 2004, and the other probably acquired abroad in 2012. Four isolates possessed the G54R, F46Y, Y431S and G448S mutations, respectively, whereas three isolates did not possess known cyp51A resistance mutations, raising the possibility of other, undetected resistance mechanisms. Routine antifungal susceptibility testing is definitively recommended in patients on long term and sub-therapeutic triazole therapy with breakthrough Aspergillus infection and recommended for all clinically relevant A. fumigatus isolates.
authors.affiliation: National Mycology Reference Centre, Microbiology & Infectious Diseases, SA Pathology, Adelaide, SA, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Kidd
authors.affiliation: Department of Microbiology, SydPath, St. Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Goeman
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.affiliation: Infectious Disease Department, Peter MacCallum Cancer Institute, Melbourne, Vic., Australia.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Slavin
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000453:epidemiology / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D001315:Australia / Q000453:epidemiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense; D012189:Retrospective Studies; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus; D065819:Voriconazole
keywords: Aspergillus fumigatus; antifungal resistance; itraconazole; posaconazole; voriconazole