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Frühjahrstagung der Sektion Antimykotische Chemotherapie 2014

Paul-Ehrlich-Gesellschaft für Chemotherapie (PEG e. V.)

23. - 24.05.2014, Bonn

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The Epidemiology of Invasive Aspergillosis and Resistance Patterns of Aspergillus spp. in Germany – Interim Analysis of a Multicenter Observational Study

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  • corresponding author Maria J.G.T. Vehreschild - Uniklinik Köln, Köln
  • Axel Hamprecht - Uniklinik Köln, Köln
  • Thomas Adam - Charité – Universitätsmedizin Berlin, Berlin
  • Oliver Bader - Universitätsmedizin Göttingen, Göttingen
  • Caroline Becker - Klinikum der RWTH Aachen, Aachen
  • Isabelle Bekerdijan-Ding - Universitätsklinikum Bonn, Bonn
  • Dieter Buchheidt - Universitätsmedizin Mannheim, Mannheim
  • Gottfried Doelken - Universitätsmedizin Greifswald, Greifswald
  • Johannes Elias - Universitätsklinikum Würzburg, Würzburg
  • Gerhard Haase - Klinikum der RWTH Aachen, Aachen
  • Corinna Hahn-Ast - Universitätsklinikum Bonn, Bonn
  • Meinolf Karthaus - Städtisches Klinikum München, München
  • Alexander Kekulé - Universitätsklinikum Halle, Halle
  • Stefan Krause
  • Silke Neumann - Universitätsmedizin Göttingen, Göttingen
  • Peter Keller - Universitätsklinikum Jena, Jena
  • Michael Kiehl - Klinikum Frankfurt (Oder), Frankfurt (Oder)
  • Holger Rohde - Uniklinik Eppendorf, Hamburg
  • Paul La Rosée - Universitätsklinikum Jena, Jena
  • Markus Ruhnke - Charité – Universitätsmedizin Berlin, Berlin
  • Enrico Schalk - Universitätsklinikum Magdeburg, Magdeburg
  • Philippe Schafhausen - Uniklinik Eppendorf, Hamburg
  • Stefan Schwartz - Charité – Universitätsmedizin Berlin, Berlin
  • Gerda Silling - Universitätsklinikum Münster, Münster
  • Katrin Schulz - Universitätsmedizin Greifswald, Greifswald
  • Peter Staib - St. Antonius Hospital, Eschweiler
  • Andrew Ullmann - Universitätsklinikum Würzburg, Würzburg
  • Thomas Weber - Universitätsklinikum Halle, Halle
  • Oliver A. Cornely - Uniklinik Köln, Köln

Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG). Frühjahrstagung der Sektion Antimykotische Chemotherapie 2014. Bonn, 23.-24.05.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14sac03

doi: 10.3205/14sac03, urn:nbn:de:0183-14sac038

Published: May 19, 2014

© 2014 Vehreschild et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Introduction: Reports on increasing identification of azole-resistant Aspergillus fumigatus in clinical and environmental isolates have raised concerns with respect to the frequency and clinical relevance of resistant Aspergillus spp. in hematological high-risk patient populations.

Methods: In an observational multicenter study supported by the Deutsche José Carreras Leukämie-Stiftung e.V., the incidence of probable and proven aspergillosis according to EORTC/MSG criteria was assessed for all inpatients with acute leukemia (AML and ALL) treated at the participating hematology departments. All identified cases were documented into a web-based database (clinicalsurveys.net). Information on risk factors, site of infection, symptoms, diagnosis, treatment and outcome were documented. In addition, all participating centers completed a survey on factors that may influence the incidence of invasive aspergillosis, including use of antifungal prophylaxis, availability of diagnostic measures and use of HEPA filtration. If available, the corresponding clinical isolates were sent to a central microbiology laboratory for resistance testing and if applicable, identification of resistance mechanisms.

Results: 17 centers contributed data to the study for the period of September 2011 – December 2012. 750 patients with AML were observed over a total of 1780 hospitalizations and 44,480 patient days. 189 patients with ALL were observed over a total of 630 hospitalizations and 12,848 patient days. In these populations, 46 (6.1%) and 13 (6.9%) cases of invasive aspergillosis were identified, respectively. The local incidence rates varied considerably between 0 and 10.6%. In 30 cases (50.8%) an antifungal prophylaxis had been administered. Liposomal amphotericin B was the most frequently used agent for targeted treatment (n=24; 40.7%). 64.5% achieved a favorable response to treatment and 9% had died at day 30. One case (1.7%) was caused by a multi-azole resistant Aspergillus fumigatus isolate. The resistance mechanism was identified as a TR/L98H mutation in the cyp51A gene.

Discussion: The incidence rate of invasive aspergillosis was lower than expected from previous reports. This might be associated with the frequent use of antifungal prophylaxis and a reserved attitude towards invasive diagnostic measures. While invasive disease by a multi-azole resistant isolate was observed, this seems to be a rare event in clinical practice.