Published online 9 December 2008
Haematologica, Vol 94, Issue 1, 113-122 doi:10.3324/haematol.11665
Copyright © 2009 by Ferrata Storti Foundation

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Fungal Infections

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Oliver A. Cornely^1,2, Angelika Böhme³, Dieter Buchheidt⁴, Hermann Einsele⁵, Werner J. Heinz⁵, Meinolf Karthaus⁶, Stefan W. Krause⁷, William Krüger⁸, Georg Maschmeyer⁹, Olaf Penack¹⁰, Jörg Ritter¹¹, Markus Ruhnke¹², Michael Sandherr¹³, Michal Sieniawski¹⁴, Jörg-Janne Vehreschild¹, Hans-Heinrich Wolf¹⁵, Andrew J. Ullmann¹⁶

¹ Klinik I für Innere Medizin, Klinikum der Universität Köln
² Zentrum für Klinische Studien (01KN0706), Köln
³ Onkologikum Frankfurt am Museumsufer, Frankfurt
⁴ III. Medizinische Klinik, Universitätsklinikum Mannheim gGmbH, Mannheim
⁵ Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
⁶ Klinik für Hämatologie und Onkologie, Klinikum Neuperlach, München
⁷ Medizinische Klinik 5, Hämatologie und Internistische Onkologie, Universitätsklinikum Erlangen, Erlangen
⁸ Medizinische Klinik C, Ernst-Moritz-Arndt-Universität, Greifswald
⁹ Medizinische Klinik Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Potsdam
¹⁰ Charité, Campus Benjamin Franklin, Klinik für Hämatologie und Onkologie, Berlin
¹¹ Pädiatrische Hämatologie/Onkologie, Universitätsklinikum Münster, Münster
¹² Charité Universitätsmedizin, Campus Charité Mitte, Medizinische Klinik und Poliklinik II, Berlin
¹³ Schwerpunktpraxis für Hämatologie und Onkologie, Weilheim, Germany
¹⁴ Haematological Sciences (CALS), Leech Building, Medical School, Newcastle upon Tyne, United Kingdom
¹⁵ Martin-Luther-Universität Halle-Wittenberg, Halle
¹⁶ Johannes Gutenberg-Universität, III. Medizinische Klinik, Mainz, Germany

Correspondence: Oliver A. Cornely, MD, Klinikum der Universität zu Köln, Klinik I für Innere Medizin Zentrum für Klinische Studien (BMBF 01KN0706) 50924 Köln, Germany. E-mail:oliver.cornely{at}ctuc.de

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

Key words: invasive fungal infection, antifungal prophylaxis, itraconazole, fluconazole, posaconazole, amphotericin B, liposomal.

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