Skip to main content

Advertisement

SpringerLink
Log in

Treatment of fungal infections in hematology and oncology

Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The Infectious Diseases Working Party of the German Society of Haematology and Oncology presents their guidelines for the treatment of fungal infections in patients with hematological and oncological malignancies. These guidelines are evidence-based, considering study results, case reports and expert opinions, using the evidence criteria of the Infectious Diseases Society of America (IDSA). The recommendations for major fungal complications in this setting are summarized here. The primary choice of therapy for chronic candidiasis should be fluconazole, reserving caspofungin or amphotericin B (AmB) for use in case of progression of the Candida infection. Patients with candidemia (except C. krusei or C. glabrata) who are in a clinically stable condition without previous azole prophylaxis should receive fluconazole, otherwise AmB or caspofungin. Voriconazole is recommended for the first-line treatment of invasive aspergillosis. The benefit of a combination of AmB and 5-flucytosine has not been demonstrated except in patients with cryptococcal meningitis. Mucormycosis is relatively rare. The drug therapy of choice consists of AmB, desoxycholate or liposomal formulation, in the highest tolerable dosage. Additional surgical intervention has been shown to achieve a lower fatality rate than with antifungal therapy alone. The role of interventional strategies, cytokines/G-CSF, and granulocyte transfusions in invasive fungal infections are further reviewed. These guidelines offer actual standards and discussions on the treatment of oropharyngeal and esophageal candidiasis, invasive candidiasis, cryptococcosis and mould infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Ally R, Schürmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, Hodges M, Troke P, Romero AJ and the Esophageal Candidiasis Study Group (2001) A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis 33:1447–1454

    CAS  PubMed  Google Scholar 

  2. Anaissie E, Bodey GP, Kantarjian H, David C, Barnett K, Bow E, Defelice R, Downs N, File T, Karam G, Potts D, Shelton M, Sugar A (1991) Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior AmB therapy. Am J Med 91:142–150

    CAS  Google Scholar 

  3. Bernard A, Caillot D, Couaillier JF, Casasnovas O, Guy H, Favre JP (1997) Surgical management of invasive pulmonary aspergillosis in neutropenic patients. Ann Thorac Surg 64:1441–1447

    Article  CAS  Google Scholar 

  4. Ruhnke M, Böhme A, Buchheidt D, Donhuijsen K, Einsele H, Enzensberger R, Glasmacher A, Gümbel H, Heussel CP, Karthaus M, Lambrecht E, Südhoff T, Szelényi H (2003) Diagnosis of invasive fungal infections in hematology and oncology. Ann Hematol 82 (Suppl 2) DOI 10.1007/s00277-003-0768-0

    CAS  PubMed  Google Scholar 

  5. Caillot D, Bassaris H, McGeer A, Arthur C, Prentice HG, Seifert W, de Beule K. (2001) Intravenous itraconazole followed by oral itraconazole in the treatment of invasive pulmonary aspergillosis in patients with hematologic malignancies, chronic granulomatous disease, or AIDS. Clin Infect Dis 33: e83-e90

    Article  CAS  Google Scholar 

  6. Caillot D, Casasnovas O, Bernard A, Couaillier J-F, Durand C, Cuisenier B, Solary E, Piard F, Petrella T, Bonnin A, Couillault G, Dumas M, Guy H (1997) Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 15:139–147

    CAS  PubMed  Google Scholar 

  7. Denning DW (1998) Invasive aspergillosis. Clin Infect Dis 26:781–805

    CAS  PubMed  Google Scholar 

  8. Denning DW, Ribaud P, Milpied N, Herbrecht R, Thiel E, Haas A, Ruhnke M, Lode H (2002) Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 34:563–571

    Article  CAS  PubMed  Google Scholar 

  9. Edwards JE Jr, Bodey GP, Bowden RA, Buechner T, de Pauw BE, Filler SG, Ghannoum MA, Glauser M, Herbrecht R, Kauffman CA, Kohno S, Martino P, Meunier F, Mori T, Pfaller MA, Rex JH, Rogers TR, Rubin RH, Solomkin J, Viscoli C, Walsh TJ, White M (1997) International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis 25:43–59

    PubMed  Google Scholar 

  10. Einsele H, Bertz H, Beyer J, Kiehl MG, Runde V, Kolb HJ, Holler E, Beck R, Schwerdfeger R, Schumacher U, Hebart H, Martin H, Kienast J, Ullmann AJ, Maschmeyer G, Krüger W, Niederwieser D, Link H, Schmidt CA, Oettle H, Klingebiel T (2003) Infectious complications after allogeneic stem cell transplantation - Epidemiology and interventional therapy strategies. Ann Hematol 82 (Suppl 2) DOI 10.1007/s00277-003-0772-4

  11. Ellis M, Spence D, de Pauw B, Meunier F, Marinus A, Collette L, Sylvester R, Meis J, Boogaerts M, Selleslag D, Krcmery V, von Sinner W, MacDonald P, Doyen C, Vandercam B (1998) An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal AmB for treatment of invasive aspergillosis. Clin Infect Dis 27:1406–1412

    Google Scholar 

  12. Fätkenheuer G, Buchheidt D, Cornely OA, Fuhr HG, Karthaus M, Kisro J, Leithäuser M, Salwender H, Südhoff T, Szelényi H, Weissinger F (2003) Central venous catheter (CVC)-related infections in neutropenic patients. Ann Hematol 82 (Suppl 2) DOI 10.1007/s00277-003-0769-z

    CAS  PubMed  Google Scholar 

  13. Habicht JM, Reichenberger F, Gratwohl A, Zerkowski HR, Tamm M (1999) Surgical aspects of resection for suspected invasive pulmonary fungal infection in neutropenic patients. Ann Thorac Surg 68:321–325

    Article  CAS  Google Scholar 

  14. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann J-W, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. New Engl J Med 347:408–415

    Article  CAS  PubMed  Google Scholar 

  15. Herbrecht R, Letscher-Bru V, Bowden RA, Kusne S, Anaissie EJ, Graybill JR, Noskin GA, Oppenheim BA, Andrès E, Pietrelli LA (2001) Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 20:460–466

    Article  CAS  Google Scholar 

  16. Heussel CP, Kauczor HU, Heussel G, Mildenberger P, Dueber C (1997) Aneurysms complicating inflammatory diseases in immunocompromised hosts: value of contrast-enhanced CT. Eur Radiol 7:316–319

    Article  CAS  PubMed  Google Scholar 

  17. Van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, Johnson PC, Tuazon CU, Kerkering T, Moskovitz BL, Powderly WG, Dismukes WE (1997) Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group. N Engl J Med 337:15–21

    Article  Google Scholar 

  18. Hübel K, Dale DC, Engert A, Liles WC (2001) Current status of granulocyte (neutrophil) transfusion therapy for infectious diseases. J Infect Dis 183:321–328

    Google Scholar 

  19. Karthaus M, Huebner G, Elser C, Geissler RG, Heil G, Ganser A (1998) Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation. Ann Hematol 77:41–45

    Article  CAS  Google Scholar 

  20. Kish MA (2001) Guide to development of practice guidelines. Clin Infect Dis 32:851–854

    Article  CAS  PubMed  Google Scholar 

  21. Kontoyiannis DP, Bodey GP (2002) Invasive aspergillosis in 2002: An update. Eur J Clin Microbiol Infect Dis 21:161–172

    Article  CAS  Google Scholar 

  22. Leenders ACAP, Daenen S, Jansen RLH, Ho WCJ, Loewenberg B, Wijermans PW, Cornelissen J, Herbrecht R, van der Lelie H, Hoogsteden HC, Verbrugh HA, de Marie S (1998) Liposomal AmB compared with AmB deoxycholate in the treatment of documented and suspected neutropenia-induced invasive fungal infections. Br J Haematol 103:205–212

    Article  CAS  PubMed  Google Scholar 

  23. Leenders AC, Reiss P, Portegies P, Clezy K, Hop WC, Hoy J, Borleffs JC, Allworth T, Kauffmann RH, Jones P, Kroon FP, Verbrugh HA, de Marie S (1997). Liposomal AmB (AmBisome) compared with AmB both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS 11:1463–1471

    Article  CAS  Google Scholar 

  24. Lin S-J, Schranz J, Teutsch SM (2001) Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 32:358–366

    CAS  PubMed  Google Scholar 

  25. Link H, Böhme A, Cornely O, Höffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW (2003) Antimicrobial therapy of unexplained fever in neutropenic patients. Ann Hematol 82 (Suppl 2) DOI 10.1007/s00277-003-0764-4

    Google Scholar 

  26. Maertens J, Raad I, Petrikkos G, Selleslag D, Petersen F, Sable C, Kartsonis N, Ngai A, Taylor A, Patterson T, Denning D, Walsh T (2002) Update of the multicenter, noncomparative study of caspofungin (CAS) in adults with invasive aspergillosis (IA) refractory (R) or intolerant (I) to other antifungal agents: analysis of 90. Abstracts of the 41th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Sep 27, 30:3269

  27. Maschmeyer G, Beinert T, Buchheidt D, Einsele H, Heussel CP, Kiehl M, Lorenz J (2003) Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients. Ann Hematol 82 (Suppl 2) DOI 10.1007/s00277-003-0765-3

    CAS  PubMed  Google Scholar 

  28. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347:2020–2029

    Article  CAS  PubMed  Google Scholar 

  29. Neely MN, Ghannoum MA (2000) The exciting future of antifungal therapy. Eur J Clin Microbiol Infect Dis 19:897–914

    CAS  PubMed  Google Scholar 

  30. Offner F (1997) Hematopoietic growth factors in cancer patients with invasive fungal infections. Eur J Clin Microbiol Infect Dis 16:56–63

    CAS  Google Scholar 

  31. Ozer H, Armitage JO, Bennett L, Crawford J, Demetri GD, Pizzo PA, Schiffer CA, Smith TJ, Somlo G, Wade JC, Wade III JL, Winn RJ, Wozniak AJ, Somerfield MR for the American Society of Clinical Oncology Growth Factors Expert Panel (2000) 2000 update of recommendations for the use of hematopoietic colony-stimulating factors: Evidence-based, clinical practice guidelines. J Clin Oncol 18:3558–3585

    CAS  PubMed  Google Scholar 

  32. Pagano L, Ricci P, Tonso A, Nosari A, Cudillo L, Montillo M, Cenacchi A, Pacilli L, Fabbiano F, del Favero A (1997) Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. Br J Haematol 99:331–336

    CAS  PubMed  Google Scholar 

  33. Phillips P, de Beule K, Frechette G, Tchamouroff S, Vandercam B, Weitner L, Hoepelman A, Stingl G, Clotet B (1998) A double-blind comparison of itraconazole oral solution and fluconazole capsules for the treatment of oropharyngeal candidiasis in patients with AIDS. Clin Infect Dis 26:1368–1373

    CAS  Google Scholar 

  34. Price TH, Bowden RA, Boeckh M, Bux J, Nelson K, Liles WC, Dale DC (2000) Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 95:3302–3309

    CAS  PubMed  Google Scholar 

  35. Rex JH, Bennett JE, Sugar AM, Pappas PG, van-der-Horst CM, Edwards JE, Washburn RG, Scheld WM, Karchmer AW, Dine AP, Levenstein MJ, Webb CD (1994) A randomized trial comparing fluconazole with AmB for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute . N Engl J Med 331:1325–1330

    Google Scholar 

  36. Rex JH, Pappas PG, Karchmer AW, Sobel J, Edwards JE, Hadley S, Brass C, Vazquez JA, Chapman SW, Horowitz HW, Zervos M, McKinsey D, Lee J, Babinchak T, Bradsher RW, Cleary JD, Cohen DM, Danziger L, Goldman M, Goodman J, Hilton E, Hyslop NE, Kett DH, Lutz J, Rubin RH, Scheld WM, Schuster M, Simmons B, Stein DK, Washburn RG, Mautner L, Chu TC, Panzer H, Rosenstein RB, Booth J; National Institute of Allergy and Infectious Diseases Mycoses Study Group (2003) A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis 36:1221-1228

    Article  CAS  PubMed  Google Scholar 

  37. Rex JH, Walsh TJ, Sobel JD, Filler SG, Pappas G, Dismukes WE, Edwards JE (2000) Practice guidelines for the treatment of candidiasis. Clin Infect Dis 30:662–678

    CAS  PubMed  Google Scholar 

  38. Saag MS, Graybill RJ, Larsen RA (2000) Practice guidelines for the management of cryptococcal disease. Clin Infect Dis 30:710–771

    Article  CAS  Google Scholar 

  39. DeShazo RD, Chapin K, Swain RE (1997) Fungal sinusitis. N Engl J Med 337:254–259

    Article  CAS  PubMed  Google Scholar 

  40. Sobel JD, Vazquez JA (1999) Fungal infections of the urinary tract. World J Urol 17:410–414

    Article  CAS  Google Scholar 

  41. Stevens DA, Kann VL, Judson MA, Morrison VA, Dummer S, Denning DW, Bennett JE, Walsh TJ, Patterson TF, Pankey GA (2000) Practice guidelines for diseases caused by aspergillus. Clin Infect Dis 30:696–709

    CAS  PubMed  Google Scholar 

  42. Stevens DA, Lee JY (1997) Analysis of compassionate use itraconazole therapy for invasive aspergillosis by the NIAID Mycoses Study Group Criteria. Arch Intern Med 157:1857–1862

    Article  CAS  Google Scholar 

  43. Sutton DA, Sanche SE, Revankar SG, Fothergill AW, Rinaldi MG (1999) In vitro amphotericin B resistance in clinical isolates of aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Micorbiol 37:2343–2345

    CAS  Google Scholar 

  44. Tedder M, Spratt JA, Anstadt MP, Hedge SS, Tedder SD, Lowe JE (1994) Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg 57:1044–1050

    CAS  PubMed  Google Scholar 

  45. Walsh TJ (1998) Primary cutaneous aspergillosis—an emerging infection among immunocompromised patients. Clin Infect Dis 27:453–457

    CAS  PubMed  Google Scholar 

  46. Walsh TJ, Hiemenz JW, Seibel NL, Perfect JR, Horwith G, Lee L, Silber JL, DiNubile MJ, Reboli A, Bow E, Lister J, Anaissie EJ (1998) AmB lipid complex for invasive fungal infections: Analysis of safety and efficacy in 556 cases. Clin Infect Dis 26:1383–1396

    CAS  PubMed  Google Scholar 

  47. Wilcox CM, Darouiche RO, Laine L, Moskovitz BL, Mallegol I, Wu J (1997) A randomized, double-blind comparison of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. J Infect Dis 176:227–232

    CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully thank Professor Jürgen Ritter, Department of Pediatric Hematology and Oncology, University of Münster, Germany, for interdisciplinary support and critical comments. We would like to thank Particia Meinhardt for her assistance in writing the the manuscript. A. Böhme was supported by the Ministry of Education and Research, Competence Network for Acute and Chronic Leukemias, Germany, Grant No 01GI 9971.

Author information

Authors and Affiliations

  1. Medizinische Klinik III, J.W. Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Angelika Böhme

  2. Med. Klinik und Poliklinik II, Schwerpunkt Onkologie u. Hämatologie, Campus Charité Mitte, Humboldt-Universität, Berlin, Germany

    Markus Ruhnke

  3. III. Med. Klinik, Universitätsklinikum Mannheim, Ruprechts-Karl-Universität Heidelberg, Mannheim, Germany

    Dieter Buchheidt

  4. Med. Klinik II, Ev. Johannes-Krankenhaus, Bielefeld, Germany

    Meinolf Karthaus

  5. Med. Klinik u. Poliklinik, Abt. und Lehrstuhl II, Universitätsklinikum, Tübingen, Germany

    Hermann Einsele

  6. Klinik u. Poliklinik für Herz-, Thorax- und Gefäßchirurgie, Johannes Gutenberg-Universität, Mainz, Germany

    Stefan Guth

  7. III. Med. Klinik u. Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany

    Gudrun Heussel

  8. Klinik u. Poliklinik für Radiologie, Johannes Gutenberg-Universität, Mainz, Germany

    Claus-Peter Heussel

  9. Abt. Hämatologie/Onkologie, Universitätsklinikum, Rostock, Germany

    Christian Junghanss

  10. Innere Med. II/Infektiologie, Med. Universitätsklinik, Freiburg, Germany

    Winfried K. Kern

  11. II. Medizin, Hämatologie/Onkologie/Infektionskrankheiten, Städt. Klinikum, Karlsruhe, Germany

    Thomas Kubin

  12. Med. Klinik, Schwerpunkt Hämatologie u. Onkologie, Universitätsklinikum Charité Campus Virchow-Klinikum, Humboldt-Universität Berlin, Germany

    Georg Maschmeyer

  13. Med. Klinik und Poliklinik II, Schwerpunkt Onkologie u. Hämatologie, Campus Charité Mitte, Humboldt-Universität, Berlin, Germany

    Orhan Sezer

  14. Med. Klinik A, Hämatologie/Onkologie, KMT-Zentrum, Westfälische-Wilhelms-Universität, Münster, Germany

    Gerda Silling

  15. Medizinische Klinik der Ruhr-Universität, Knappschaftskrankenhaus, Bochum, Germany

    Thomas Südhoff

  16. Med. Klinik III, Schwerpunkt Hämatologie, Onkologie u. Transfusionsmedizin, Universitätsklinikum Benjamin Franklin, Berlin, Germany

    Hubert Szelényi†

  17. III. Med. Klinik u. Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany

    Andrew J. Ullmann

Authors
  1. Angelika Böhme
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus Ruhnke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dieter Buchheidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meinolf Karthaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hermann Einsele
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Stefan Guth
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gudrun Heussel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claus-Peter Heussel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christian Junghanss
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Winfried K. Kern
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Thomas Kubin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Georg Maschmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Orhan Sezer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Gerda Silling
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Thomas Südhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Hubert Szelényi†
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Andrew J. Ullmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Angelika Böhme.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Böhme, A., Ruhnke, M., Buchheidt, D. et al. Treatment of fungal infections in hematology and oncology. Ann Hematol 82 (Suppl 2), S133–S140 (2003). https://doi.org/10.1007/s00277-003-0767-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-003-0767-1

Keywords

Search

Navigation