Loading

Fungal Infections – Primary Prophylaxis

Societies
dgho sghssh oegho sgmo
This document is not the most recent version. Please view Antimykotische Primärprophylaxe bei Patienten mit hämatologischen Neoplasien

Fungal Infections – Primary Prophylaxis

Status: January 2012
Authors: Oliver A. Cornely, Dieter Buchheidt, Angelika Böhme, Hermann Einsele, Werner Heinz, Meinolf Karthaus, Stefan Krause, William H. Krüger, Georg Maschmeyer, Olaf Penack, Jörg Ritter, Markus Ruhnke, Michael Sandherr, Michael Sieniawski, Jörg Janne Vehreschild, Hans-Heinrich Wolf, Andrew J. Ullmann
on behalf of the AGIHO Infectious Diseases Working Party of the DGHO

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

Definition

A

Good evidence to support a recommendation for use

B

Moderate evidence to support a recommendation for use

C

Poor evidence to support a recommendation for use

D

Moderate evidence to support a recommendation against use

E

Good evidence to support a recommendation against use

Quality of Evidence

Definition

I

Evidence from ≥1 properly randomized, controlled trial

II

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

III

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 
Algorithm for Primary Prophylaxis of Fungal Infections

3References

  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

4Drugs and Dose

Table 2: Antifungal Prophylaxis  

Substance

Dose

Application

Amphotericin, liposomal

12,5 mg twice weekly

Inhalation

Fluconazole

1 x 400 mg daily

PO

Posaconazole

3 x 200 mg daily

PO

5[Kapitel nicht relevant]

6[Kapitel nicht relevant]

7[Kapitel nicht relevant]

8[Kapitel nicht relevant]

9[Kapitel nicht relevant]

11Active Studies

12Authors‘ Affiliations

Prof. Dr. med. Oliver A. Cornely
Uniklinik Köln, Klinik I für Innere Med.
Zentrum für Klinische Studien
Infektiologie-Hämatologie-Onkologie
Kerpener Str. 62
50937 Köln
Prof. Dr. med. Dieter Buchheidt
Klinikum Mannheim GmbH
Medizinische Fakultät Mannheim
III. Medizinische Klinik
Theodor-Kutzer-Ufer 1-3
68167 Mannheim
PD Dr. med. Angelika Böhme
Onkologikum
Frankfurt | Am Museumsufer
Zum Lauenburger Hof 76, 11.Stck.
60594 Frankfurt
Prof. Dr. med. Hermann Einsele
Universitätsklinikum Würzburg
Medizinische Klinik und Poliklinik II
Oberdürrbacher Str. 6
97080 Würzburg
PD Dr. med. Werner Heinz
Kliniken Nordoberpfalz AG
Klinikum Weiden
Med. Klinik I
Söllnerstr.16
92637 Weiden
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
Ferdinand-Sauerbruch-Str.
17487 Greifswald
Prof. Dr. med. Georg Maschmeyer
Klinikum Ernst von Bergmann
Zentrum für Innere Medizin
Klinik für Hämatologie, Onkologie
und Palliativmedizin
Charlottenstr. 72
14467 Potsdam
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
Lukas-Krankenhaus Bünde
Hämatologie/ Internistische Onkologie
Hindenburgstr. 56
32257 Bünde
PD Dr. med. Michael Sandherr
Gemeinschaftspraxis
für Hämatologie und Onkologie mit Tagesklinik
Röntgenstr. 4/II
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. Jörg Janne Vehreschild
Universitätsklinikum Frankfurt
Medizinische Klinik 2
Theodor-Stern-Kai 7
60590 Frankfurt
Dr. med. Hans-Heinrich Wolf
Südharzklinikum
Klinik für Innere Medizin III
Hämatologie, Onkologie, Hämostaseologie
Dr.-Robert-Koch-Str. 39
99734 Nordhausen
Univ.-Prof. Dr. med. Andrew J. Ullmann
Universitätsklinik Würzburg
Julius-Maximilians-Universität
Medizinische Klinik & Poliklinik II
Oberdürrbacher Str. 6
97080 Würzburg

Comments