Azole Resistance of Environmental and Clinical Aspergillus fumigatus Isolates from Switzerland

ABSTRACT Aspergillus fumigatus is a ubiquitous opportunistic pathogen. This fungus can acquire resistance to azole antifungals due to mutations in the azole target (cyp51A). Recently, cyp51A mutations typical for environmental azole resistance acquisition (for example, TR34/L98H) have been reported. These mutations can also be found in isolates recovered from patients. Environmental azole resistance acquisition has been reported on several continents. Here we describe, for the first time, the occurrence of azole-resistant A. fumigatus isolates of environmental origin in Switzerland with cyp51A mutations, and we show that these isolates can also be recovered from a few patients. While the TR34/L98H mutation was dominant, a single azole-resistant isolate exhibited a cyp51A mutation (G54R) that was reported only for clinical isolates. In conclusion, our study demonstrates that azole resistance with an environmental signature is present in environments and patients of Swiss origin and that mutations believed to be unique to clinical settings are now also observed in the environment.

[1]  A. Chowdhary,et al.  Clinical implications of globally emerging azole resistance in Aspergillus fumigatus , 2016, Philosophical Transactions of the Royal Society B: Biological Sciences.

[2]  B. Zwaan,et al.  In-host adaptation and acquired triazole resistance in Aspergillus fumigatus: a dilemma for clinical management. , 2016, The Lancet. Infectious diseases.

[3]  D. Sanglard,et al.  Identification of Aspergillus fumigatus multidrug transporter genes and their potential involvement in antifungal resistance. , 2016, Medical mycology.

[4]  J. Baddley,et al.  Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial , 2016, The Lancet.

[5]  W. Melchers,et al.  Azole Resistance in Aspergillus fumigatus: Can We Retain the Clinical Use of Mold-Active Antifungal Azoles? , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  A. Chowdhary,et al.  Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: Is it de novo or environmentally acquired? , 2015, Journal of global antimicrobial resistance.

[7]  P. Hauser,et al.  Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus , 2015, Emerging infectious diseases.

[8]  U. Groß,et al.  Environmental Isolates of Azole-Resistant Aspergillus fumigatus in Germany , 2015, Antimicrobial Agents and Chemotherapy.

[9]  E. Rietschel,et al.  Prevalence and molecular characterization of azole resistance in Aspergillus spp. isolates from German cystic fibrosis patients. , 2014, The Journal of antimicrobial chemotherapy.

[10]  G. Lorenzis,et al.  Azole-resistant Aspergillus fumigatus in the environment of northern Italy, May 2011 to June 2012. , 2014, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[11]  K. Lagrou,et al.  Azole resistance in Aspergillus fumigatus: a growing public health concern. , 2013, Current opinion in infectious diseases.

[12]  K. Lagrou,et al.  AZOLE RESISTANCE IN ASPERGILLUS: AN EMERGING PROBLEM? , 2012, Acta clinica Belgica.

[13]  W. Melchers,et al.  Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR34/L98H Azole Resistance Mechanism , 2012, Journal of Clinical Microbiology.

[14]  J. Turnidge,et al.  Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Triazoles and Six Aspergillus spp. for the CLSI Broth Microdilution Method (M38-A2 Document) , 2010, Journal of Clinical Microbiology.

[15]  N. Keller,et al.  Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis , 2009, Clinical Microbiology Reviews.

[16]  J. Meis,et al.  Utility of CSP typing to sub-type clinical Aspergillus fumigatus isolates and proposal for a new CSP type nomenclature. , 2009, Journal of microbiological methods.

[17]  W. Melchers,et al.  Possible Environmental Origin of Resistance of Aspergillus fumigatus to Medical Triazoles , 2009, Applied and Environmental Microbiology.

[18]  W. Melchers,et al.  Academic Editor: Chris Kibbler, Royal Free Hospital London, United Kingdom , 2007 .

[19]  Raoul Herbrecht,et al.  Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  G. Fink,et al.  Coding Tandem Repeats Generate Diversity in Aspergillus fumigatus Genes , 2007, Eukaryotic Cell.

[21]  W. Melchers,et al.  A New Aspergillus fumigatus Resistance Mechanism Conferring In Vitro Cross-Resistance to Azole Antifungals Involves a Combination of cyp51A Alterations , 2007, Antimicrobial Agents and Chemotherapy.

[22]  J. Perfect,et al.  Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. , 2007, The New England journal of medicine.

[23]  Richard Sylvester,et al.  Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. , 2002, The New England journal of medicine.

[24]  J. Perfect,et al.  NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis. , 1994, The American journal of medicine.

[25]  J. Enders,et al.  Infectious Diseases Society of America. , 1969, Antimicrobial agents and chemotherapy.

[26]  W. Melchers,et al.  Azole, polyene and echinocandin MIC distributions for wild-type, TR34/L98H and TR46/Y121F/T289A Aspergillus fumigatus isolates in the Netherlands. , 2015, The Journal of antimicrobial chemotherapy.

[27]  Clinical,et al.  Reference method for broth dilution antifungal susceptibility testing of filamentous fungi : Approved standard , 2008 .

[28]  D. Sanglard,et al.  Azole and fungicide resistance in clinical and environmental Aspergillus fumigatus isolates. , 2005, Medical mycology.