Report June Working group of the. Under the auspices of

Transkript

1 Global Emerging Fungal Infection Registry Initiated in 2003 Report June 2013 Working group of the Under the auspices of Supported by unrestricted grants from Astellas Pharma, Gilead Sciences, Merck and Pfizer

2 Table of Contents Study Co-ordinators... 3 Introduction... 6 Current Results Achievements and Goals Presentations Publications Awards Recent Accomplishments Goals for Contact Information Contributors Members Report June von 33

3 Study Co-ordinators Clinical ID Microbiology Molecular Biology Pharmacology Pathology Austria Elisabeth Presterl, MD Allgemeines Krankenhaus - Universitätskliniken Wien Währinger Gürtel Wien T F elisabeth.presterl@meduni wien.ac.at Cornelia Lass-Flörl, MD Institute of Hygiene, Microbiology and Social Medicine Universität Innsbruck Fritz-Pregl-Str Innsbruck T F cornelia.lass-floerl@uibk.ac.at Walter Buzina, MD Institut für Hygiene Medizinische Universität Universitätsplatz Graz T F walter.buzina@meduni-graz.at Ulrich Strasser. MD Institut für Pathologie Medizinische Universität Innsbruck Müllerstr. 44 A-6020 Innsbruck T F ulrich.strasser@i-med.ac.at Brazil Marcio Nucci, MD Hospital Universitário Universidade Federal do Rio de Janeiro Av. Brigadeiro Trompovsky S/N Rio de Janeiro T F mnucci@hucff.ufrj.br Czech Republic Zdeněk Ráčil, MD Dept. of Internal Medicine Hemato-Oncology University Hospital Brno Jihlavska Brno T /3642 F zracil@fnbrno.cz Iva Kocmanova, MD Dept. of Microbiology University Hospital Brno, Jihlavska Brno T ikocmanova@fnbrno.cz Martina Lengerova, MD Dept. of Internal Medicine Hemato-Oncology University Hospital Brno Jihlavska Brno T mlengerova@nbrno.cz Mojmir Moulis, MD Dept. of Pathology University Hospital Brno Jihlavska Brno T mmoulis@fnbrno.cz Ludmila Malaskova, MD Dept. of Biochemistery University Hospital Brno Jihlavska Brno T lmalas@fnbrno.cz Report June von 33

4 Clinical ID Microbiology Molecular Biology Pharmacology Pathology Oliver A. Cornely, MD, FIDSA, FACP Klinikum der Universität Klinik I für Innere Medizin Köln T F oliver.cornely@ctuc.de Axel Hamprecht, MD Klinikum der Universität Institut f. Mikrobiologie, Immunologie u. Hygiene Goldenfelsstr Köln T F +49-(0) axel.hamprecht@uk-koeln.de Ralf Bialek, MD MVZ Labor Dr. Krause Steenbeker Weg Kiel T bialek@labor-krause.de Fedja Farowski, Biochemist Klinikum der Universität Institut für Pharmakologie Köln T F fedja.farowski@ctuc.de Birgid Markiefka Klinikum der Universität Institut für Pathologie Köln birgid.markiefka@uk-koeln.de Volker Rickerts, MD Robert Koch Institute Postbox: Berlin T rickertsv@rki.de India Anupma Jyoti Kindo, MD Dept. of Microbiology Sri Ramachandra Medical College/Research Institute No.1, Ramachandra Nagar Porur, Chennai, T F anupmalakra@yahoo.com Report June von 33

5 Clinical ID Microbiology Molecular Biology Pharmacology Pathology Israel Morad Wattad, MD Rabin Medical Center Infectious Diseases Unit 39 Jabotinski St Petah Tikva T F Moradv@clalit.org.il Italy Livio Pagano, MD Dipartimento di Ematologia Universita Cattolica del Sacro Cuore (Roma) Largo Francesco Vito Roma T F lpagano@rm.unicatt.it Maurizio Sanguinetti, MD Istituto di Microbiologia (Roma) Università Cattolica del Sacro Cuore Largo Francesco Vito Roma T F msanguinetti@rm.unicatt.it Annamaria Tortorano, MD Dip. Sanità Pubblica- Microbiologia-Virologia Milano Università di Milano Via Pascal, 36/ Milano T F annamaria.tortorano@unimi.it Andrea Novelli, MD Dipartimento di Farmacologia Università degli Studi di Firenze Viale Pieraccini, Firenze T F andrea.novelli@unifi.it Gianluigi Vago, MD Department of Clinical Sciences Luigi Sacco Hospital University of Milan Via Pascal, 36/ Milano T F gianluca.vago@unimi.it Turkey Sevtap Arikan-Akdagli, MD Mycology Laboratory (Ankara) Hacettepe University Ankara F +90 (312) sevtap.arikan@gmail.com Report June von 33

6 Introduction The incidence of invasive fungal infections (IFI) is increasing in all parts of the world. The etiology for this ongoing epidemiological development is not completely understood. However, major contributing factors are the increasing number of transplantation procedures undertaken around the world (estimated at 500,000 per year), a widening of the indications for intensive chemotherapy, and the growing number of other clinical conditions requiring immunosuppressive treatment. Therapeutic standards have been developed for the most frequent IFI, i.e. candidiasis, aspergillosis and cryptococcosis. However, the so called emerging fungi are also a reason for the increased number of IFIs. Thus, clinicians are now facing infections due to a variety of different fungi without any reliable treatment recommendations and therapeutic decision making is not evidence based. Prevalence of emerging fungi is virtually unknown and there is an additional knowledge gap in pathogen biology, since isolates have not been collected systematically. In order to overcome the lack of knowledge on epidemiology, clinical course, biology and pathomechanisms, and finally to develop an evidence based diagnostic-therapeutic integrated approach of IFI caused by emerging fungi, Fungiscope - A Global Emerging Fungal Infection Registry has been created. Fungiscope uses a web-based electronic case form accessible via For inclusion into the registry patients require cultural, histopathological, serological or molecular evidence of IFI and the associated clinical symptoms and signs. The clinical data on underlying disorder and IFI will be collected and stored in an internet-based database. Additionally, the pathogen strains and samples of infected tissue are collected, examined and stored in a bio-bank the Fungithek. The clinical and biological data are subsequently evaluated and analysed. Figure 1a and b present the data / sample flow and overall project structure. The clinical database and the bio-bank are connected and accessable to the public via a web-based search engine - FungiQuest (figure 2). In the following report we introduce the most current results and achievements. We also discuss future goals and ongoing developments of the project. Report June von 33

7 Figure 1a: Project structure Report June von 33

8 Figure 1b: Material flow Report June von 33

9 Figure 2: FungiQuest database search engine Report June von 33

10 Current Results Until now, 340 cases have been documented and considered valid. The most frequently registered pathogens were Mucorales (previously termed Zygomycetes) (n=146; 42.9%), Fusarium spp. (n=55; 16.2%), yeasts (n=48; 14.1%), and Dematiaceae (n=34; 10.0%) followed by Penicillium spp. / Paecilomyces spp. (n=16; 4.7%) and Scedosporium spp. (n=14; 4.1%) (figure 3). The majority of patients were Caucasian followed by Asian and North/South American Indian origins (figure 4). The contribution of cases by country is shown in figure 5. Sites of infection differ among pathogens, see figure 6. In patients with invasive mucormycosis, the lungs were the most commonly involved organs with an incidence of 69.2%. Other involved sites were the paranasal sinuses (22.6%), deep soft tissues (15.8%) and the central nervous system (13.7%). Fusarium spp. infections most frequently presented as blood stream infections (52.7%) or skin infections (47.3%). Other commonly affected sites were lungs (34.5%) and deep soft tissues (20.0%). Infections with Dematiaceae mostly involved the eyes, paranasal sinuses, deep soft tissues, and skin (range from 11.8% %). By contrast, yeasts were most often diagnosed from blood cultures (66.7%) followed by pulmonary infections (27.1%). The evaluation of risk factors for the development of IFI revealed differences between individual pathogens shown in figure 7. The most common risk factors for developing an infection with Mucorales and Fusarium spp. were chemotherapy (54.8% and 56.4% respectively) or haematopoetic stem cell transplantation (HSCT) (approximately 30%) followed by ICU stay and diabetes mellitus, with rates of %. Chemotherapy was also the most common risk factor in patients presenting with yeast infections (47.9%). In addition, 33.3% of patients were treated in intensive care units. Further risk factors were diabetes mellitus (14.6%) and solid organ transplantation, chronic pulmonary disease, and haematopoetic stem cell transplantation (12.5% respectively). By contrast, patients with a Dematiaceae infection presented most frequently with diabetes mellitus (47.1%) and/or chronic renal disease (17.6%). All-cause-mortality, mortality due to fungal infection and response to treatment differed among individual pathogens and are shown in figure 8. The highest all-cause-mortality was observed in patients with mucormycosis (59.6%), followed by patients with yeast (52.1%) and Fusarium spp. infections (49.1%). When looking at the mortality due to the fungal infection it was highest in infections caused by Mucorales (45.2%) followed by yeast (37.5%) and Fusarium spp (38.2%). By contrast, the lowest all-cause-mortality was revealed in patients with Dematiaceae, equaling only 5.9%. None of these deaths was due to the fungal infection. The highest rates of complete and partial remissions were observed in patients with IFI caused by Dematiaceae and Penicillium/Paecilomyces spp (73.5 and 68.8% respectively). Patients with a Mucorales infection displayed the lowest rate of response to treatment (41.1%). In conclusion, the clinical relevance of invasive fungal infections by emerging fungi is increasing. In a short time, actual cases from several countries world-wide could be documented and showed a broad spectrum of pathogens. Further investigators and coordinators are encouraged to contribute to the success of Fungiscope. Report June von 33

11 Mucorales (previously Zygomycetes) Fusarium spp Yeast Dematiaceae Penicillium/Paecilomyces Scedosporium Other Figure 3: Distribution of 340 pathogens by major groups Report June von 33

12 Figure 4: Ethnicities Report June von 33

13 Figure 5: Contributing coutries Report June von 33

14 Mucorales (previously Zygomycetes) (n=146) Fusarium spp (n=55) Chemotherapy 55% Chemotherapy 56% HSCT 32% HSCT 31% ICU stay 29% ICU stay 20% Diabetes mellitus 16% Diabetes mellitus 13% 0% 10% 20% 30% 40% 50% 60% 0% 10% 20% 30% 40% 50% 60% Yeasts (n=48) Dematiaceae (n=34) Chemotherapy 48% ICU stay 33% Diabetes mellitus 15% Chronic pulmonary disease 13% Solid organ transplant 13% HSCT 13% Major surgery 10% Chronic renal disease 10% 0% 10% 20% 30% 40% 50% 60% Diabetes 47% Chronic renal disease 18% 0% 10% 20% 30% 40% 50% Figure 6: Risk factors for major groups Report June von 33

15 Mucorales (previously Zygomycetes) (n=146) Fusarium spp (n=55) Lungs 69% Blood 53% Paranasal Sinus Soft tissue Central nervous system Bones GI-Tract 23% 16% 14% 13% 12% Skin Lungs Soft tissue Paranasal Sinus 13% 20% 35% 47% Skin 10% Eyes 13% 0% 20% 40% 60% 80% 0% 10% 20% 30% 40% 50% 60% Yeasts (n=48) Dematiaceae (n=34) Blood Lungs 27% 67% Eyes 32% Liver 15% Paranasal Sinus 27% Central nervous system Kidney 13% 13% Soft tissue 24% Soft tissue 10% Skin 12% 0% 10% 20% 30% 40% 50% 60% 70% 80% 0% 5% 10% 15% 20% 25% 30% 35% Figure 7: Sites of infection for major groups Report June von 33

16 80% 74% 70% 60% 60% 50% 40% 49% 52% 45% 38% 38% 41% 51% 52% 30% 20% 10% 0% 6% Mortality Mortality due to IFI Favourable outcome 0% Mucorales Fusarium spp. Yeasts Dematiaceae Figure 8: Outcomes for major group Report June von 33

17 Achievements and Goals Presentations April 27 30, rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Berlin, October 19-23, 2012 Annual Congress of the German Society for Hematology and Oncology (DGHO), Stuttgart, September 9-12, nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, CA, USA June 23-26, th Congress of the International Society for Human and Animal Mycology, Berlin, April 25-28, th Congress of Infectious Diseases and Tropical Medicine, Cologne, March 31-April 3, nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), London, UK January 24-25, rd WATL-Congress, Berlin, October 2-5, th Trends in Medical Mycology (TIMM), Valencia, Spain September 30-Oct. 4, 2011 Annual Congress of the German Society for Hematology and Oncology (DGHO), Basel, Switzerland September 17-21, th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Chicago, USA September 1-3, th Congress of the German Society for Mycology (DMykG e.v.), Kiel, May 7-10, st ECCMID/27th ICC, Joint Congress of the European Society of Clinical Microbiology and Infectious Diseases and the International Society of Chemotherapy20th, Milan, Italy March 31-April 2, 2011 Annual Congress of the German Society for Infectious Diseases (DGI), Leipzig, October 1-5, 2010 Annual Congress of the German Society for Hematology and Oncology (DGHO), Berlin, September 12-15, th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), MA, Boston, USA September 9-11, th Congress of the German Society for Mycology (DMykG e.v.), Vienna, Austria June 23-26, th Congress of Infectious Diseases and Tropical Medicine, Cologne, June 18-19, 2010 MSD Workshop Infektionen in der Hämatologie, Munich, May 7-8, 2010 Paul-Ehrlich-Gesellschaft für Chemotherapie e.v., Spring Meeting of the Sektion Antimykotische Chemotherapie, Bonn, April 10-13, th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna, Austria Report June 2013 Page 17 of 33

18 Publications May 2013 Pagano L, Cornely O, Caira M, Cesaro S, Gasbarrino C, Girmenia C, Heinz WJ, Herbrecht R, Lass-Flörl C, Nosari A, Potenza L, Racil Z, Rickerts V, Sheppard DC, Simon A, Ullmann AJ, Valentini CG, Vehreschild JJ, Candoni A, Vehreschild MJ. Combined antifungal approach for the treatment of invasive mucormycosis in patients with hematological diseases: a report from the SEIFEM and FUNGISCOPE registries. Haematologica 2013 May 28, Epub ahead of print January 2013 Christopeit M, Lindner A, Surov A, Weber T, Vehreschild MJ, Bialek R, Schmoll HJ.Right flank pain and high fever in a neutropenic patient with acute lymphoblastic leukaemia. Mycoses 2013, Jan; 56(1):90-92 October 2011 de Hoog GS, Robert V, Lackner M, Vehreschild MJ, Vehreschild JJ, Symoens F, Göttlich-Fligg E, Garcia- Hermoso D, Harun A, Meyer W, Chen SC, Hamprecht A, Fischer G, Buzina W, Cornely OA, Guarro J, Cano J, Horré R Making moulds meet. Information retrieval as a basis for understanding Pseudallescheria and Scedosporium Mycoses Oct;54 Suppl 3:1-4 December 2009 M.J.G.T. Rüping, W.J. Heinz, A.J. Kindo, V. Rickerts, C. Lass-Flörl, C. Beisel, R. Herbrecht, Y. Roth, G. Silling, A.J. Ullmann, K. Borchert, G. Egerer, J. Maertens, G. Maschmeyer, A. Simon, M. Wattad, G. Fischer, J.J. Vehreschild, O.A. Cornely Forty-one Recent Cases of Invasive Zygomycosis from a Global Clinical Registry J Antimicrob Chemother Feb;65(2): July 2008 Rüping M.J.G.T., Albermann N., Ebinger F., Burckhard I., Beisel C., Müller C., Vehreschild J.J., Kochanek M., Fätkenheuer G., Bangard C., Ullmann A.J., Herr W., Kolbe K., Hallek M., Cornely O.A. Posaconazole concentrations in the central nervous system. J Antimicrob Chemother 2008 Dec;62 (6): Awards Young Investigator Award 2010 (Nachwuchsförderpreis) of the German Society for Mycology (DMykG e.v.) awarded to Dr. M.J.G.T. Vehreschild for her work on Fungiscope Report June 2013 Page 18 of 33

19 Recent Accomplishments Launch of new, improved website in March 2013 Initiation of the MSG Phaeohyphomycosis Registry by use of the Fungiscope database in October 2012 Manuscript of joint analysis with Brazilian Fusarium spp group (Prof Nucci, Rio de Janeiro, Brazil) submitted Database restructuring including: o Re-evaluation of all cases with respect to classification according to EORTC/MSG criteria o Harmonizing different wording used for documentation o Structural adjustments facilitating data export and analysis o Incorporation of FungiThek into the database Abstracts accepted for presentation at ICAAC, Annual Meeting of the German Society for Infectious Diseases and TIMM 2013 Goals for Publication of a subset analysis on rare yeasts, including resistance patterns Publication of a comparison between sequencing and morphological results for the first 100 Fungiscope isolates Extending the FungiQuest platform (online since April 2010): o Faster inclusion of new cases o Inclusion of FungiThek / isolate information o Improved search-engine Report June 2013 Page 19 of 33

20 Contact Information Chair: Oliver A. Cornely, MD, FIDSA, FACP Coordinating Physicians: Maria J.G.T. Vehreschild (née Rüping), MD Kerstin Wahlers, MD Technical advisor, site operator clinicalsurveys.net: Jörg J. Vehreschild, MD Uniklinik Köln Infectious Diseases Clinical Trials Unit II BH E15 R64 Kerpener Strasse Köln T F Report June 2013 Page 20 of 33

21 Contributors Austria Section of Infectious Diseases, Department of Medicine, Medical University of Graz, Austria Institut für Hygiene, Mikrobiologie und Sozialmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria Belgium Martin Hoenigl Cornelia Lass-Flörl Experimentele Laboratoriumgeneeskunde, UZ Leuven, 3000 Leuven, Belgium University Hospital Gasthuisberg, Leuven, Belgium Brazil Edith Vermeulen Johan Maertens, Isabel Spriet Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil Denise Pereira Infection Control Dept., Santa Casa Complexo Hospitalar, Universidade Federal do Rio Grande do Sul, Brazil Canada Alessandro Pasqualotto Service de Maladies Infectieuses, Département de Pédiatrie, McGill University, Montreal, Canada Departments of Medicine & Microbiology and Immunology, McGill University, Montreal, Canada Cuba Philipe Ovetchkine Don Sheppard Instituto de Hematologia e Imunologia, Habana, Cuba Czech Republic Alberto Arencibia Núñez Dept. of Internal Medicine, Hematology/Oncology, Faculty Hospital Brno, Brno, Czech Republic Denmark Zdenek Racil Dept. of Hematology, Copenhagen University Hospital, Copenhagen, Denmark France Emil Hermansen Hematology and Oncology, University Hospital of Strasbourg Hautepierre Hospital, Strasbourg, France Raoul Herbrecht Report June 2013 Page 21 of 33

22 Hämato-Onkologie, Uniklinik Aachen, Aachen, Pädiatrische Hämatologie und Onkologie Infektiologie, Zentrum der Kinderheilkunde, Universität zu Bonn, Bonn, Klinikum Dortmund Nord, Abteilung Pneumologie/Infektiologie, Dortmund, Medizinische Klinik 5 Hämatologie und Internistische Onkologie, Uniklinik Erlangen, Erlangen, Abt. Hämatologie und Onkologie, Georg-August-Universität, Goettingen, Institut für Medizinische Mikrobiologie, Universitätsklinikum Essen, Essen, Hämatologie und Onkologie, Universitätsklinikum Freiburg, Freiburg, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie - Transplantationszentrum Universitätsklinikum der Ernst-Moritz-Arndt- Universität Greifswald, Greifswald, Klinik für Innere Medizin IV, Onkologie und Hämatologie, Martin-Luther- University Halle-Wittenberg, Halle, Department of Pulmonary Medicine, Hannover Medical School Uniklinik Heidelberg Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin, Jena, Jena University Hospital, Division of Gastrology, Hepatology and infectious Diseases, Jena, Klinik I für Innere Medizin, Uniklinik Köln, Köln, III. Medizinische Klinik und Poliklinik, Johannes Guttenburg Universität Mainz, Mainz Deutschand Medizinische Poliklinik, Klinikum der Universität München-Großhadern, Muenchen, Klinik und Poliklinik für Kinderheilkunde Pädiatrische Hämatologie/Onkologie - Uniklinik Münster, Münster, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Potsdam, Klinik und Poliklinik für Innere Medizin, Abteilung für Hämatologie und Onkologie, Universitätsklinikum Rostock, Rostock, Klinik III für Innere Medizin, Uniklinik Ulm, Ulm, Carolin Becker Arne Simon Stefanie Später Stefan Kallert Silke Neumann Jörg Steinmann Hartmut Bertz Katrin Schulz Hans-Heinrich Wolf Matthias Pletz Martina Gronkowski Bernd Gruhn Stephanie Beier Oliver Cornely, Fedja Farowski, Maria Vehreschild, Jörg Janne Vehreschild, Kerstin Wahlers Andrew Ullmann Johannes Bogner Andreas Groll Georg Maschmeyer Kersten Borchert Georg Härter Report June 2013 Page 22 of 33

23 Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg, Medizinische Klinik 5, Hämatologie & Internistische Onkologie, Universitätsklinikum Erlangen, Erlangen, Greece Werner Heinz, Andrew Ullmann, Anna Kuhn Lisa Meintker Attikon University Hospital, Emergency and Critical Care, Athens, Greece Elisabeth Paramythiotou Hungary Semmelweis University, 1st Clinic for Internal Medicine, Budapest, Hungary Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Clinical Microbiology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary India Judit Demeter Lorant Hatvani László Bereczki Department of Microbiology, Sri Romachandra Medical College and RI, Porur, India Israel Kindo, Anupma Department of Otolaryngology Head & Neck Surgery, Edith Wolfson Medical Center, Holon, Israel Hadassah University Medical Center, Jerusalem, Israel Infectious Diseases Unit, Rabin Medical Center, Petah Tikva, Israel Shaare Zedek Medical Center, Infectious disease unit, Jerusalem, Israel Italy Yehudah Roth Maya Korem Morad Wattad Eli Ben-Chetrit Department of Biomedical Science and Human Oncology Hygiene Section, University of Bari, Bari, Italy Oncoematologia Pediatrica, Policlinico G.B. Rossi, Verona, ItalyClinica di Oncoematologia Pediatrica, Azienda Ospedaliera Padova, Padova, Italy Maria Teresa Montagna Simone Cesaro Istituto di Microbiologia, Universita Cattolica del Sacro Cuore, Rome, Italy Maurizio Sanguinetti Netherlands Department of Medical Microbiology, Canisius-Wilhelmina Hospital, Nijmegen, Netherlands Romania Jacques Meis Department of Mycology-Mycotoxicology, Universitatea Petre Andrei, Iasi, Romania Mihai Mares Report June 2013 Page 23 of 33

24 Russia Department of Clinical Mycology, Allergology and Immunology, St. Petersburg Medical Academy of Postgraduate Education, St. Petersburg, Russia Slovakia Nikolay Klimko Sofya Khostelidi National Cancer Institute, Bratislava, Slovakia Thailand Lubos Drgona Division of Infectious Diseases and Tropical Medicine, Khon Kaen University, Khon Kaen, Thailand Turkey Ploenchan Chetchotisakd Department of Medicine, Section of Infectious Diseases, Hacettepe University Medical School, Ankara, Turkey Akdeniz University Medical Faculty, Department of Clinical Microbiology, Antalya, Turkey USA Sevtap Arikan Dilara Ogunc Department of Infectious Diseases, Section of Transplant Infectious Diseases, Medicine Institute and Transplant Center, Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, Ohio, USA Sherif Beniameen Mossad Members Argentina El Centro de Internación de FUNDALEU, Departamento Medico, Buenos Aires, Argentina Instituto Nacional de Enfermedades Infecciosas "Dr. C. G. Malbrán", Buenos Aires, Argentina Centro de Referencia de Micología Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina Australia Maria Cecilia Dignani Susana Cordoba Marisa Biasoli Department of Microbiology & Infectious Diseases, Royal Perth Hospital, Perth, Australia Christopher Heath Report June 2013 Page 24 of 33

25 Austria Anästhesiologie und Intensivmedizin, Landesklinikum Thermenregion Baden, Baden, Austria Franz Schwameis Klinik für Pneumologie, Inselspital, Universitätsspital Bern, Bern, Austria Sebastian Ott Institut für Hygiene, klinische Bakteriologie und Mykologie, Medizinische Universität Graz, Graz, Austria Walter Buzina Institut für Hygiene, Mikrobiologie und Sozialmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Austria Anna Huppert, Isabella Schalk Ulrich Strasser Krankenhaushygiene, Landeskrankenhaus Klagenfurt, Klagenfurt, Austria Ulrich Zerlauth Kinder- Herzzentrum Linz, Allgemeines Krankenhaus Linz, Linz, Austria Klinik für Anästhesiologie, Wagner-Jauregg Nervenklinik, Linz, Austria Universitätsinstitut für Medizinische Mikrobiologie, Hygiene und Infektiologie - SALK Labor GmbH, Salzberger Universitätsklinikum, Salzberg, Austria Institut für Anästhesie und Intensivmedizin, Landeskrankenhaus Steyr, Steyr, Austria Abt. f. Anästhesie und Intensivmedizin, Wilhelminenspital Wien, Wien, Austria Infektionen und Tropenmedizin, Universitätsklinik I für Innere Medizin, Medizinische Universität Wien, Wien, Austria Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Austria Belgium Werner Moosbauer Udo Illievich Markus Hell Achim von Goedecke Peter Wimmer Christina Kratzer, Elisabeth Presterl Katharina Pfistershammer University Hospital Gasthuisberg, Leuven, Belgium Brazil Katrien Lagrou, Johan Maertens, Isabel Spriet Serviço de Oncohematologia / TMO, Hospital Univ. Prof. Edgard Santos - UFBA, Salvador, Bahia, Brazil Laboratory of Mycology, Hospital das Clinicas, Federal University of Paraná, Curitiba, Brazil Hematology and Mycology Laboratory, Hospital Universitário Clementino Fraga, UFRJ, Rio de Janeiro, Brazil Canada Marco Aurélio Salvino, Monica Botura Flávio de Queiroz Telles Marcio Nucci Department of Medicine, Peter Lougheed Center, Calgary, Canada Microbiology and Infectious Diseases, SMBD - Jewish General Hospital, Montreal, Canada Andrew Johnson Mark Miller Report June 2013 Page 25 of 33

26 Laboratoire de santé publique du Quebec, Secteur Mycologie, Sainte- Anne-de Bellevue (Quebec), Canada Internal Medicine Residency Program, Juravinski Hospital and Cancer Centre, St. Hamilton/Ontario, Canada Medical Microbiology Division of Medical Microbiology and Infection Control JPPN 1112A Microbiology, Vancouver, Canada Chile Philippe Dufresne Shariq Haider Diane Roscoe Unidad de Infectología, Clínica Alemana, Santiago de Chile, Chile Facultad de Medicina, Universidad de Valparaíso, Chile China Luis Thompson Thomas Weitzel Institute of Hematology, Peking University People's Hospital, Beijing, China Department of Hematology, Guangdong General Hospital, Guangdong, China Zhejiang University, School of Medicine, The First Affiliated Hospital, Bone Marrow Transplant Center, Hangzhou Zeijiang, China Changhai Hospital, Department of Hematology, Shanghai P.R., China Columbia Feng-Rong Wang Xin Du He Huang Jian-Min Yang Conjunto Residencial Montevideo, Medellin, Columbia Croatia Angela Restrepo, Angela Tobón Division of Haematology, Zagreb University Hospital Centre, Zagreb, Croatia Czech Republic Nemet Damir, Vrohvac Radovan Dept. of Microbiology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic Denmark Petr Hamal Dept. of Hematology, Copenhagen University Hospital, Copenhagen, Denmark France Jannik Helweg- Larsen Département d'hématologie, Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris, and Université Denis Diderot, Paris, France Emmanuel Raffoux, Patricia Ribaud Report June 2013 Page 26 of 33

27 II. Medizinische Klinik, Einheit für Stammzelltransplantation, Klinikum Augsburg, Augsburg, Rheumatologische Ambulanz, Sana Rheumazentrum Rheinland-Pfalz AG, Bad Kreuznach, Klinik für Hämatologie und Onkologie, Vivantes Krankenhaus, Berlin, Klinik für Neurochirurgie, Charité-Universitätsmedizin Berlin, Berlin, Medizinische Klinik und Poliklinik II, Charité-Universitätsmedizin Berlin, Berlin, Klinik für Neurologie, Helios-Klinikum Berlin-Buch, Berlin, Robert Koch Institut, Abteilung für Infektionskrankheiten,Berlin, Klinik für Hämatologie, Onkologie & Palliativmedizin, Städt. Kliniken Bielefeld gem.gmbh, Bielefeld, Gastroenterologie & Infektiologie, St. Josef Hospital, Klinikum der Ruhr- Universität Bochum, Bochum, Klinik für Neonatologie, Universität zu Bonn, Bonn, Division of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, Borstel, Medizinische Klinik I, Klinikum Bremen-Mitte, Bremen, Klinikum Dortmund Nord, Abteilung Pneumologie/Infektiologie, Dortmund, Dermatologie, Krankenhaus Dresden-Friedrichstadt, Dresden, Christoph Schmid Eckhard Weber Jörg Beyer, Markus Müller Olaf Süss Markus Ruhnke Franz-Josef Dieste Volker Rickerts, Michael Seibold Martin Görner Renate Schlottmann Cornelia Graef Christoph Lange Henrike Thomssen Bernhard Schaaf, Greta Ullrich Gesina Hansel Medizinische Klinik und Poliklinik I, Uniklinik Dresden, Dresden, Ulrich Schuler Mykologisches Labor, Krankenhaus Dresden-Friedrichstadt, Dresden, HNO-Klinik, Universitätsklinikum Düsseldorf, Düsseldorf, Klinik für Hämatologie, Onkologie und Klin. Immunologie, Universitätsklinikum Düsseldorf, Düsseldorf, Institut für Tropenmedizin, Universitätsklinikum Düsseldorf, Düsseldorf, Hämatologie / Internist. Onkologie, Uniklinik Erlangen, Erlangen, Medizinische Klinik 5, Hämatologie & Internistische Onkologie, Universitätsklinikum Erlangen, Erlangen, Klinik für Hämatologie/Internistische Onkologie und Stammzelltransplantation, Kliniken Essen Süd, Essen, Klinik für Knochenmarktransplantation, Universitätsklinikum Essen, Essen, Klinik für Nephrologie, Universitätsklinikum Essen, Essen, Uniklinik Frankfurt, Frankfurt, Irina Vennewald Katrin Gollner, Kathrin Scheckenbach Thomas Schröder Stefan Reuter Wolf Rösler Stefan Krause Mohammed Wattad Rudolf Trenschel Oliver Witzke Volker Rickerts Report June 2013 Page 27 of 33

28 Zentrum für Kinder- und Jugendmedizin, Klinik III, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Abteilung für Innere Medizin, Hämatologie u.onkologie, Klinikum Frankfurt, Infektiologikum Frankfurt, Frankfurt, Onkologikum Frankfurt, Frankfurt, Hämatologie und Onkologie, Universitätsklinikum Freiburg, Freiburg, Universitätsklinikum Freiburg, Freiburg, Zentrum für Infektiologie und Reisemedizin, Universitätsklinikum Freiburg, Freiburg, Institut für Medizinische Mikrobiologie, Universitätskliniken Göttingen, Göttingen, Klinik und Poliklinik für Innere Medizin C, Hämatologie und Onkologie - Transplantationszentrum Universitätsklinikum der Ernst-Moritz-Arndt- Universität Greifswald, Greifswald, Klinik für Innere Medizin IV, Onkologie und Hämatologie, Martin-Luther- University Halle-Wittenberg, Halle, Thomas Lehrnbecher Michael Kiehl Gaby Knecht Angelika Böhme Werner C. Neubauer Helmut Lang Dirk Wagner Uwe Groß William Krüger Hans-Heinrich Wolf Institut für Infektiologie, Asklepios Klinik St. Georg, Hamburg, M. Sabranski Thoraxklinik-Heidelberg, Heidelberg, Abteilung für Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg, Medizinische Klinik und Poliklinik V, Universitätsklinikum Heidelberg, Heidelberg, Medizinische Klinik und Poliklinik II, Universitätsklinikum Schleswig- Holstein, Kiel, MVZ Labor Dr. Krause und Kollegen, Kiel, Klinik und Poliklinik für Orthopädie, Uniklinik Köln, Köln, Institut für Hygiene, Kliniken der Stadt Köln, Krankenhaus Merheim, Köln, Klinik für Anaesthesiologie und Operative Intensivmedizin, Klinikum Konstanz, Konstanz, Institut für Pathologie, Universitätsklinikum Leipzig, Leipzig, Institut für Medizinische Mikrobiologie und Hygiene, Universität Lübeck, Lübeck, Interdisziplinäres Zentrum für Palliativmedizin, Agaplesion Markus Krankenhaus, Frankfurt am Main, III. Medizinische Klinik, Universitätsklinikum Mannheim, Mannheim, Department of Infectious Diseases and Tropical Medicine, Ludwig- Maximilians-Universität München, Muenchen, Kinderkardiologie und Pädiatrische Intensivmedizin, Klinikum der Universität München-Großhadern, München, Maren Schuhmann Johann Wilhelm Schier Gerlinde Egerer Heinz-A. Horst Ralf Bialek Rolf Sobottke Frauke Mattner Wolfgang Krüger Claudia Wickenhauser Jan Rupp Sabine Mousset Anne Dietz Thomas Loescher Markus Loeff Report June 2013 Page 28 of 33

29 Klinik für Hals-, Nasen- und Ohrenheilkunde, Klinikum der Universität München-Großhadern, München, Klinik f. Hämato-Onkologie, Klinikum Harlaching, Städtisches Klinikum München GmbH, München, Klinik und Poliklinik für Kinderheilkunde Pädiatrische Hämatologie/Onkologie - Uniklinik Münster, Münster, Medizinische Klinik A, KMT-Zentrum, Uniklinik Münster, Münster, Medizinische Klinik III, Klinikum der Universität München-Großhadern, München, Hämatologie/Onkologie/Immunologie/Rheumatologie, Klinikum Schwäbisch Gmünd, Stauferklinik, Mutlangen, Klinik und Poliklinik für Innere Medizin, Abteilung für Hämatologie und Onkologie, Universitätsklinikum Rostock, Rostock, Hämatologie und Onkologie, Medizinische Klinik I, Kliniken Sindelfingen, Sindelfingen, Klinik für Dermatologie, University of Tübingen, Tübingen, Abteilung für Kinder- und Jugendmedizin, Marienhospital Witten, Witten, Medizinische Klinik 5 Hämatologie und Internistische Onkologie, University of Witten/Herdecke, Köln, Medizinische Klinik und Poliklinik II, Universität Würzburg, Würzburg, Greece Robert Guerkov Meinolf Karthaus, Xavier Schiel Jörg Ritter Gerda Silling Helmut Ostermann, Lisa Peterson Holger Hebart Lena Diestel, Michael Schmitt Stefan Neuburger Sybille Schmidt Bahman Gharavi Stefan Sauerland Jürgen Löffler, Hartwig Klinker, Bhanu Sinha 1st Department of Propaedeutic Medicine, Athens University, Athens, Greece Cystic Fibrosis Department, Aghia Sophia Children s Hospital, Athens, Greece Infectious Diseases and Antimicrobial Chemotherapy Research Laboratory, Athens University, Athens, Greece Laboratory for Clinical Microbiology, Attikon University General Hospital, Athens, Greece India Anna Skiada Stavros Doudounakis George L. Petrikkos Joseph Meletiadis MSD Pharmaceuticals Pvt. Ltd. India, Associate Director Medical Affairs, India Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India Dept. of Microbiology, Centre for Basic Sciences, Kasturba Medical College, Manipal University, Manipal, India Pramod Gawli Arunaloke Chakrabarti Ritesh Agarwal Prakash Yegneswaran Report June 2013 Page 29 of 33

30 Indonesia Department of Internal Medicine University of Indonesia, Faculty of Medicine University of Indonesia, Mangunkusumo Hospital, Jakarta, Indonesia Ireland Erni J Nelwan Dept. of Bacteriology, Belfast City Hospital, Belfast, Ireland Trinity College, Dublin Saint James Hospital, Dublin, Ireland Israel John E. Moore Thomas Rogers Shaare Zedek Medical Center, Infectious disease unit, Jerusalem, Israel Sheba Medical Center Israel, Tel Aviv, Israel Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Italy Eli Ben-Chetrit Nathan Keller Ronen Ben-Ami Dipartimento di Farmacologia, Università degli Studi di Firenze, Firenze, Italy Divisione di Ematologia e Trapianto di Midollo Osseo, Ospedale San Martino, Genova, Italy Laboratorio di Micologia Medica, Sezione Sanità Pubblica, University of Milan, Milan, Italy Pathology Unit, Luigi Sacco Hospital, University of Milan, Milan, Italy Dipartimento di Ematologia, Universita Cattolica del Sacro Cuore, Rome, Italy Hematology Unit, San Camillo-Forlanini Hospital, Rome, Italy Japan Andrea Novelli Andrea Bacigalupo Annamaria Tortorano Gianluigi Vago Livio Pagano Mariagrazia Garzia Division of Control and Treatment of Infectious Diseases, Chiba University Hospital, Chiba, Japan Nagasaki University Hospital, Nagasaki, Japan Seirei Hamamatsu General Hospital, Shizuoka, Japan Korea Katsuhiko Kamei, Akira Watanabe Shigeru Kohno Shinichiro Morioka Hematology-Oncology Clinic, Hematopoietic Stem Cell Transplantation Center, Center for Specific Organs Cancer, Research Institute and Hospital, National Cancer Center, Korea Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea Kuwait Hyeon Seok Eom Joon Seong Park Microbiology Department, Health Sciences Center, Kuwait, Kuwait Eiman Mokaddas Report June 2013 Page 30 of 33

31 Lebanon American University of Beirut Medical Center, Beirut, Lebanon Lithuania Souha Kanj- Sharara Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania Marius Miglinas Vilnius University Hospital, Department of Hematology, Vilnius, Lithuania Indre Klimiene Mexico Hospital Civil de Guadalajara, Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico, IXtlamatia Clinical Research S.A. de C.V, Mexico City, Mexico Hospital General de Culiacán, Sinaloa, Mexico Netherlands Eduardo Rodriguez-Noriega Miguel Ángel Reséndiz Ramón Rivas Llamas University Medical Center Groningen, Groningen, the Netherlands Peru Jan P. Arends Hematology/ BMT Department, Rebagliati National Hospital, Lima, Peru Portugal Eduardo Fernandez-Vertiz Coimbra University Hospital, Coimbra, Portugal Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal Serbia Rui Tome Rita Caramalho Serbian Society of Medical Mycology (SSMM), National Medical Mycology Reference Laboratory - NMMRL, Belgrade, Serbia Singapore Valentina Arsic Arsenijevic Infectious Diseases Care, Mount Elizabeth Medical Centre, Singapore National University Health System, University Medicine Center, Division of Infectious Diseases, NUHS Tower Block, Level 10, Singapore National University Health System, University Children\'s Medical Institute, Department of Pediatrics, Singapore, Singapore South Africa Asok Kurup Chai Louis Yin Ann Si Min Chan Report June 2013 Page 31 of 33

32 Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa Nelson R. Mandela School of Medicine, Durban, South Africa Spain Robert Dunn Teke Apalata Grupo Andaluz de Leucemias Agudas GALA, Hospital Juan Ramón Jiménez-Huelva, Huelva, Spain Servicio de Hematología de la Unidad de Consejo y Cuidado Oncológico de Sanitas, Hospital de la Princesa, Madrid, Spain Hospital Universitario Marqués De Valdecilla, Department of Hematology, Santander, Spain Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla, Spain Hospital Univ. La Fe, Servicio Microbiología, Unidad de Micología, Valencia, Spain Department of Hematology, University Hospital La Fe, Valencia, Spain, Valencia, Spain Sweden Eusebio Martín Chacón Rafael de la Cámara Lucrecia Yanez San Sugundo Martin-Pena Almudena Javier Peman Rebeca Rodriguez Veiga Clinical Micrbiological Laboratory, Sunderby Hospital, Luleå, Luleå, Sweden Switzerland Peter Cettner Abt. für Spitalhygiene und Spitalepidemiologie, Universitätsspital Basel, Basel, Switzerland Division of Infectious Dieseases & Hospital Epidemiology, Universitätsspital Basel, Basel, Switzerland Medizin I Abteilung für Hämatologie, Universitätsspital Basel, Basel, Switzerland Institut für Infektionskrankheiten, Bern, Switzerland Universitätsklinik für Pneumologie, Inselspital, Universitätsspital Bern, Bern, Switzerland University Hospital Lausanne (CHUV), Lausanne, Switzerland Taiwan Andreas Widmer U. Flueckiger Alois Gratwohl Stefan Zimmerli Sebastian Ott Andrej Trampiz Far Eastern Memorial Hospital, Taipei, Taiwan Tai-Chen Stem Cell Therapy Center, National Taiwan University, Taipeh, Taiwan Chiaying Liu Jih-Luh Tang Division of Infectious Diseases, Department of Internal Medicine, Center Yee-Chun Chen For Infection Control, National Taiwan University Hospital, Taipei, Taiwan Turkey Department of Medicine, Section of Infectious Diseases, Hacettepe University Medical School, Ankara, Turkey Murat Akova, Omrun Uzun Report June 2013 Page 32 of 33

33 Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Baskent University, Ankara, Turkey Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Division of Hematology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey United Kingdom Can Boga Serhat Imamoglu Fatih Demirkan, Omur Gokmen Sevindik Southern General Hospital, Glasgow, United Kingdom Department of Infection, St George's University of London, London, United Kingdom Princess Royal University Hospital, South London Healthcare NHS Trust, Farnborough Common, Orpington, Kent, United Kingdom NPHS Microbiology ABM (Swansea and Bridgend), Wales, United Kingdom USA Nitish Khanna Jon Lambourne M. Mansour Ceesay Nidhika Berry Division of Medical Microbiology, Department of Pathology The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Pathology, University of Colorado, Denver, USA Division of Infectious Diseases Director, Microbiology & Infectious Diseases Translational Research Center Henry Ford Hospital, Wayne State University School of Medicine, Detroit, MI MiraVista Diagnostics and MiraBella Technologies, Indianapolis, Indiana, USA Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA Division of Infectious Diseases, University of Washington Office, Washington, USA Sean Zhang Diane Hutchinson Jose. A Vazquez Patricia Connolly Linda Boyken Philip Coffin Report June 2013 Page 33 of 33