International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus.
An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome(®)). In regions with environmental resistance rates of ≥10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class.
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: Paul.Verweij@radboudumc.nl.
Paul E
PE
Verweij
General Medicine and Infectious Diseases Units, Alfred Health, Melbourne, Australia.
Michelle
M
Ananda-Rajah
University of Wisconsin School of Medicine and Public Health, Madison, USA.
David
D
Andes
Unit of Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark.
Maiken C
MC
Arendrup
Department of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands.
Roger J
RJ
Brüggemann
Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Anuradha
A
Chowdhary
1st Department of Internal Medicine, Clinical Trials Centre Cologne - BMBF 01KN1106, Centre for Integrated Oncology CIO Köln Bonn, and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany.
Oliver A
OA
Cornely
National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
David W
DW
Denning
Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Paediatric Haematology/Oncology, University Children's Hospital, Muenster, Germany.
Andreas H
AH
Groll
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Koichi
K
Izumikawa
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Bart Jan
BJ
Kullberg
Department of Microbiology and Immunology and National Reference Center for Mycosis, Universitaire Ziekenhuizen Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
Katrien
K
Lagrou
Department of Haematology, Universitaire Ziekenhuizen Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
Johan
J
Maertens
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Jacques F
JF
Meis
National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Pippa
P
Newton
National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Iain
I
Page
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
Seyedmojtaba
S
Seyedmousavi
Departments of Medicine, and Microbiology and Immunology, McGill University, Montreal, Canada.
Donald C
DC
Sheppard
Division of Infectious Diseases, University of Genova (DISSAL), A.O.U. IRCCS San Martino-IST, Genoa, Italy.
Claudio
C
Viscoli
Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Adilia
A
Warris
Department of Haematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
J Peter
JP
Donnelly
D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000302:isolation & purification; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology; D015195:Drug Design; D025141:Drug Resistance, Fungal; D026141:Drug Resistance, Multiple, Fungal; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests; D055732:Pulmonary Aspergillosis / Q000188:drug therapy / Q000382:microbiology
D000935:Antifungal Agents; D001393:Azoles
Aspergillus fumigatus; Azole resistance; Chronic aspergillosis; Invasive aspergillosis; Voriconazole