International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus

Paul E. Verweij*, Michelle Ananda-Rajah, David Andes, Maiken C. Arendrup, Roger J. Bruggemann, Anuradha Chowdhary, Oliver A. Cornely, David W. Denning, Andreas H. Groll, Koichi Izumikawa, Bart Jan Kullberg, Katrien Lagrou, Johan Maertens, Jacques F. Meis, Pippa Newton, Iain Page, Seyedmojtaba Seyedmousavi, Donald C. Sheppard, Claudio Viscoli, J. Peter DonnellyAafje Warris

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

258 Citations (Scopus)
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Abstract

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 (R)). 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. (C) 2015 The Authors. Published by Elsevier Ltd.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalDrug Resistance Updates
Volume21-22
DOIs
Publication statusPublished - 2015

Bibliographical note

Acknowledgements
We thank Gilead Sciences Europe Ltd., UK for financially supporting logistical aspects of this study. The logistics of the meeting were handled by Congress Care, Den Bosch, The Netherlands. The sponsor was not involved in the selection of the participants or procedures, or in the discussion, data collection, analysis or writing of the manuscript. The medical writer was financially supported by the Dutch Society for Medical Mycology and the Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Keywords

  • Azole resistance
  • Invasive aspergillosis
  • Chronic aspergillosis
  • Aspergillus fumigatus
  • Voriconazole
  • Chronic pulmonary aspergillosis
  • Central-nervous-system
  • Liposomal amphotericin-B
  • Pharmacodynamic Target Determination
  • Bronchoalveolar lavage fluid
  • Antifungal Therapy
  • TR34/L98H Mutations
  • CYP51A gene
  • Wild-type

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