Fungal Infections – Primary Prophylaxis

Date of document January 2012

1Definition and Basic Information

The rising incidence of invasive fungal infections compromises therapeutic outcomes in hematologic cancer patients and in transplant recipients. This guideline is based on a systematic literature search for clinical trials on antifungal prophylaxis [1]. Data were extracted by two of the authors. A review committee with experts for hematology and infectious diseases discussed and interpreted the data in a consensus process. A total of 86 studies were identified including 16,922 patients. Only few trials yielded significant differences in efficacy. Fluconazole 400 mg/day improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, in patients with acute myeloid leukemia or myelodysplastic syndrome. Posaconazole 600 mg/day reduced the incidence of invasive fungal infections and the attributable mortality of patients with graft versus host disease after allogeneic stem cell transplantation and in patients with acute myeloid leukemia or with myelodysplastic syndrome. In the latter group, posaconazole prophylaxis led to a significant decrease in overall mortality. Aerolized liposomal amphotericin B reduced the incidence of invasive pulmonary aspergillosis.

Categories are based on the evaluation of study results and the recommendations developed by the Infectious Diseases Society of America, ISDA, see Table 1.

Table 1: Categories of Evidence  

Category, grade Strength of Recommendation



Good evidence to support a recommendation for use


Moderate evidence to support a recommendation for use


Poor evidence to support a recommendation for use


Moderate evidence to support a recommendation against use


Good evidence to support a recommendation against use

Quality of Evidence



Evidence from ≥1 properly randomized, controlled trial


Evidence from ≥1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferable from >1 centre); from multiple time series; or from dramatic results of uncontrolled experiments


Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports from expert committees

2Primary Prophylaxis

Posaconazole 600 mg/day is recommended in patients with acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) or undergoing allogeneic stem cell recipients for the prevention of invasive fungal infections and reduction of mortality [A-I] [23]. Flucanozole 400 mg/day is recommended in allogeneic stem cell recipients until development of graft versus host disease [A-I] [45]. Aerolized liposomal amphotericin B is recommended during prolonged neutropenia [B-II] [6].

The algorithm for primary prophylaxis is depicted of fungal infections is depicted in Figure 1.

Figure 1: Algorithm for Primary Prophylaxis of Fungal Infections 

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  1. Oliver A. Cornely, Angelika Böhme, Dieter Buchheidt, Hermann Einsele, Werner J. Heinz, Meinolf Karthaus, Stefan W. Krause, William Krüger, Georg Maschmeyer, Olaf Penack, Jörg Ritter, Markus Ruhnke, Michael Sandherr, Michal Sieniawski, Jörg-Janne Vehreschild, Hans-Heinrich Wolf, and Andrew J. Ullmann: 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. Haematologica. 2009, 94:113–122. DOI:10.3324/haematol.11665

  2. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 1992;326:845-51. PMID:1542320

  3. Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study. J Infect Dis 1995;171:1545-52. PMID:7769290

  4. Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007;356:348-359. http://content.nejm.org/cgi/content/abstract/356/4/348?ijkey=f0258d123c5ce59d3c5d8839d2407c1416824d6f&keytype2=tf_ipsecsha

  5. Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007;356:335-347 http://content.nejm.org/cgi/content/full/356/4/335?ijkey=f9ed79644e3af0e3b49a4567c6bf6ac946cb28c9

  6. Rijnders BJ, Cornelissen JJ, Slobbe L, Becker MJ, Doorduijn JK, Hop WC, et al. Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin Infect Dis 2008;46:1401-8. DOI:10.1086/586739

10Drugs and Dose

Table 2: Antifungal Prophylaxis  




Amphotericin, liposomal

12,5 mg twice weekly



1 x 400 mg daily



3 x 200 mg daily


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15Active Studies

16Authors‘ Affiliations

PD Dr. med. Angelika Böhme
Onkologikum Frankfurt am Museumsufer
Hochstr. 29
60313 Frankfurt am Main
Prof. Dr. med. Dieter Buchheidt
Prof. Dr. med. Oliver A. Cornely
Uniklinik Köln, Klinik I für Innere Med.
Zentrum für Klinische Studien
Kerpener Str. 62
50937 Köln
Prof. Dr. med. Hermann Einsele
Universitätsklinikum Würzburg
Medizinische Klinik und Poliklinik II
Oberdürrbacher Str. 6
97080 Würzburg
Prof. Dr. med. Werner Heinz
Caritas-Krankenhaus Bad Mergentheim
Med. Klinik 2
Uhlandstr. 7
97980 Bad Mergentheim
Prof. Dr. med. Meinolf Karthaus
Klinikum Neuperlach
Klinik für Hämatologie und Onkologie
Oskar-Maria-Graf-Ring 51
81737 München
Prof. Dr. med. Stefan Krause
Universitätsklinikum Erlangen
Medizinische Klinik 5
Hämatologie und Intern. Onkologie
Ulmenweg 18
91054 Erlangen
Prof. Dr. med. William H. Krüger
Ernst-Moritz-Arndt-Universität Greifswald
Klinik und Poliklinik für Innere Medizin C
Hämatologie und Onkologie
17487 Greifswald
Prof. Dr. med. Georg Maschmeyer
Deutsche Gesellschaft für Hämatologie
und Medizinische Onkologie (DGHO)
Bauhofstr. 12
10117 Berlin
Prof. Dr. med. Olaf Penack
Charité - Universitätsmedizin Berlin
CVK: Campus Virchow-Klinikum
CC 14: Tumormedizin
Augustenburger Platz 1
13353 Berlin
Prof. Dr. med. Jörg Ritter
Prof. Dr. med. Markus Ruhnke
Helios Klinikum Aue
Klinik für Hämatologie/Onkologie
und Palliativmedizin
Gartenstr. 6
08280 Aue
PD Dr. med. Michael Sandherr
MVZ Penzberg
Schwerpunktpraxis für Hämatologie und Onkologie
Filialpraxis Weilheim
Röntgenstr. 4
82362 Weilheim
Dr. med. Michael Sieniawski
Northern Institute for Cancer Research
Academic Haematology
Medical School
Newcastle University
Framlington Place
UK-NE2 4HH Newcastle Upon Tyne
Univ.-Prof. Dr. med. Andrew J. Ullmann
Universitätsklinik Würzburg
Medizinische Klinik & Poliklinik II
Oberdürrbacher Str. 6
97080 Würzburg
Univ.-Prof. Dr. med. Jörg Janne Vehreschild
Universitätsklinikum Frankfurt
Medizinische Klinik 2
Theodor-Stern-Kai 7
60590 Frankfurt
Dr. med. Hans-Heinrich Wolf
Klinik für Innere Medizin III
Hämatologie, Onkologie, Hämostaseologie
Dr.-Robert-Koch-Str. 39
99734 Nordhausen


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