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Prophylaxis of invasive fungal infections in patients with hematological malignancies and solid tumors

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

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Abstract

Morbidity and mortality in patients with malignancies, especially leukemia and lymphoma, are increased by invasive fungal infections. Since diagnosis of invasive fungal infection is often delayed, antifungal prophylaxis is an attractive approach for patients expecting prolonged neutropenia. Antifungal prophylaxis has obviously attracted much interest resulting in dozens of clinical trials since the late 1970s. The non-absorbable polyenes are probably ineffective in preventing invasive fungal infections, but may reduce superficial mycoses. Intravenous amphotericin B and the newer azoles were used in clinical trials, but their role in antifungal prophylaxis is still not well defined. Allogeneic stem cell transplant recipients are at particularly high risk for invasive fungal infections. Other well described risk factors are neutropenia >10 days, corticosteroid therapy, sustained immunosuppression, graft versus host disease, and concomitant viral infections. The enormous study efforts are contrasted by a scarcity of risk stratified evidence based recommendations for clinical decision making. The objective of this review accumulating information on about 10.000 patients is to assess evidence based criteria primarily regarding the efficacy of antifungal prophylaxis in neutropenic cancer patients.

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References

  1. Abbas J, Bodey GP, Hanna HA, Mardani M, Girgawy E, Abi-Said D, Whimbey E, Hachem R, Raad I (2000) Candida krusei fungemia. An escalating serious infection in immunocompromised patients. Arch Intern Med 160: 2659–2664

    CAS  PubMed  Google Scholar 

  2. Akiyama H, Mori S, Tanikawa S, Sakamaki H, Onozawa Y (1993) Fluconazole versus oral amphotericin B in preventing fungal infection in chemotherapy-induced neutropenic patients with haematological malignancies. Mycoses 36:373–378

    Google Scholar 

  3. Alangaden G, Chandrasekar PH, Bailey E, Khaliq Y (1994) Antifungal prophylaxis with low-dose fluconazole during bone marrow transplantation. The Bone Marrow Transplantation Team. Bone Marrow Transplant 14: 919–924

    CAS  PubMed  Google Scholar 

  4. Annaloro C, Oriana A, Tagliaferri E, Bertolli V, Della Volpe A, Soligo D, Ibatici A, Pozzoli E, Lambertenghi Deliliers GL (1995) Efficacy of different prophylactic antifungal regimens in bone marrow transplantation. Haematologica 80: 512–517

    CAS  PubMed  Google Scholar 

  5. Arning M, Scharf RE (1989) Prevention of amphotericin-B-induced nephrotoxicity by loading with sodium chloride: a report of 1291 days of treatment with amphotericin B without renal failure. Klin Wochenschr 67:1020–1028

    CAS  PubMed  Google Scholar 

  6. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34:7–14

    CAS  PubMed  Google Scholar 

  7. BitMansour A, Brown JMY (2002) Prophylactic Administration of Liposomal Amphotericin B Is Superior to Treatment in a Murine Model of Invasive Aspergillosis after Hematopoietic Cell Transplantation. J Inf Dis 186:134–137

    Google Scholar 

  8. Bodey G, Bueltmann B, Duguid W, Gibbs D, Hanak H, Hotchi M, Mall G, Martino P, Meunier F, Milliken S, et al. (1992) Fungal infections in cancer patients: an international autopsy survey. Eur J Clin Microbiol Infect Dis 11:99-109

    CAS  PubMed  Google Scholar 

  9. Bodey GP, Anaissie EJ, Elting LS, Estey E, O'Brien S, Kantarjian H (1994) Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B. Cancer 73:2099–2106

    CAS  PubMed  Google Scholar 

  10. Böhme A, Hoelzer D (2000) Primary antifungal prophylaxis with low-dose intravenous amphotericin B in hematological malignancies. Results of a pilot study. Onkologie 23:145–150

    Google Scholar 

  11. Böhme A, Just-Nübling G, Bergmann L, Shah PM, Stille W, Hoelzer D (1996) Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies. J Antimicrob Chemother 38: 953–961

    Google Scholar 

  12. Böhme A, Karthaus M, Einsele H, Ruhnke M, Sudhoff T, Buchheidt D, Enzensberger R, Szelenyi H, Glasmacher A, Just-Nubling G, Gumbel H (1999) [Diagnosis of systemic fungal infections in hematology. Standard recommendations of the Working Group for Infections in Hematology and Oncology of the German Association for Hematology and Oncology]. Dtsch Med Wochenschr 124 (Suppl 1):S24–S30

  13. Boogaerts M, Maertens J, van Hoof A, de Bock R, Fillet G, Peetermans M, Selleslag D, Vandercam B, Vandewoude K, Zachee P, De Beule K (2001) Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients. J Antimicrob Chemother 48: 97–103

    CAS  PubMed  Google Scholar 

  14. Bow EJ, Laverdiere M, Lussier N, Rotstein C, Cheang MS, Ioannou S (2002) Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer 94:3230–3246

    Article  CAS  PubMed  Google Scholar 

  15. Brammer KW (1990) Management of fungal infection in neutropenic patients with fluconazole. Haematology and Blood Transfusion 33:546–550

    Google Scholar 

  16. Brincker H (1983) Prevention of mycosis in granulocytopenic patients with prophylactic ketoconazole treatment. Mykosen 26:242–247

    CAS  PubMed  Google Scholar 

  17. Brincker H (1978) Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study. Acta Med Scand 204:123–128

    Google Scholar 

  18. Buchanan AG, Riben PD, Rayner EN, Parker SE, Ronald AR, Louie TJ (1985) Nystatin prophylaxis of fungal colonization and infection in granulocytopenic patients: correlation of colonization and clinical outcome. Clin Invest Med 8:139–147

    CAS  PubMed  Google Scholar 

  19. Capilla J, Ortoneda M, Pastor FJ, Guarro J (2001) In vitro antifungal activities of the new triazole UR-9825 against clinically important filamentous fungi. Antimicrob Agents Chemother 45:2635–2637

    Article  CAS  PubMed  Google Scholar 

  20. Chandrasekar PH, Gatny CM (1994) Effect of fluconazole prophylaxis on fever and use of amphotericin in neutropenic cancer patients. Bone Marrow Transplantation Team. Chemotherapy 40:136–143

    CAS  PubMed  Google Scholar 

  21. Cornely OA, Ullmann AJ, Karthaus M (2003) Evidence-based assessment of primary antifungal prophylaxis in patients with hematologic malignancies. Blood 101:3365–3372

    Article  CAS  PubMed  Google Scholar 

  22. Cuenca-Estrella M, Rodriguez-Tudela JL, Mellado E, Martinez-Suarez JV, Monzon A (1998) Comparison of the in-vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus. J Antimicrob Chemother 42:531–533

    Article  CAS  PubMed  Google Scholar 

  23. Denning DW (1998) Invasive aspergillosis. Clin Inf Dis 26:781–805

    CAS  Google Scholar 

  24. Doellmann T, Klimasch T, Heil G, Krauter J, Elser C, Ganser A, Karthaus M (1999) Effective prophylaxis of chronic disseminated candidiasis and pulmonary infiltrations in acute leukemia patients with intensive low-dose i.v. amphotericin B. In: Jahrestagung der Deutschen Gesellschaft für Hämatologie und Onkologie; 3.-6.10.1999; Jena; p 505

  25. Donnelly JP, Starke ID, Galton DA, Catovsky D, Goldman JM, Darrell JH (1984) Oral ketoconazole and amphotericin B for the prevention of yeast colonization in patients with acute leukaemia. J Hosp Infect 5:83–91

    CAS  PubMed  Google Scholar 

  26. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP (1999) Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 29:239–244

    CAS  PubMed  Google Scholar 

  27. Egger T, Gratwohl A, Tichelli A, Uhr M, Stebler Gysi C, Passweg J, Pless M, Wernli M, Buser U, Wuhrmann J, et al. (1995) Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study. Support Care Cancer 3:139–146

    CAS  PubMed  Google Scholar 

  28. Ellis ME, Clink H, Ernst P, Halim MA, Padmos A, Spence D, Kalin M, Hussain Qadri SM, Burnie J, Greer W (1994) Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis 13:3–11

    CAS  PubMed  Google Scholar 

  29. Erjavec Z, Woolthuis GM, de Vries-Hospers HG, Sluiter WJ, Daenen SM, de Pauw B, Halie MR (1997) Tolerance and efficacy of Amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in haematological patients. Eur J Clin Microbiol Infect Dis 16:364–368

    CAS  PubMed  Google Scholar 

  30. Estey E, Maksymiuk A, Smith T, Fainstein V, Keating M, McCredie KB, Freireich EJ, Bodey GP (1984) Infection prophylaxis in acute leukemia. Comparative effectiveness of sulfamethoxazole and trimethoprim, ketoconazole, and a combination of the two. Arch Intern Med 144:1562–568

    Article  CAS  PubMed  Google Scholar 

  31. Finke R (1990) [Comparison of oral fluconazole and amphotericin B prophylaxis against fungal infections in the neutropenic phase of patients treated with antileukemic agents]. Mycoses 33 (Suppl 1):42-54

    Google Scholar 

  32. Glasmacher A, Hahn C, Molitor E, Marklein G, Sauerbruch T, Schmidt-Wolf IG (1999) Itraconazole through concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-beta-cyclodextrin oral solution or coated-pellet capsules. Mycoses 42:591–600

    Google Scholar 

  33. Glasmacher A, Hahn C, Molitor E, Marklein G, Schmidt-Wolf I (2001) Itraconazole for Antifungal Prophylaxis in Neutropenic Patients: a Meta-Analysis of 2181 Patients. In: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; September and December 2001, Chicago, p 378

  34. Glasmacher A, Hahn C, Molitor E, Sauerbruch T, Marklein G, Schmidt-Wolf IGH (1999) Definition of a Minimal Effective Trough Concentration of Itraconazole for Antifungal Prophylaxis in Severely Neutropenic Patients with Hematologic Malignancies. In: Microbiology ASf, editor. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 1999, San Francisco, USA, p 566

  35. Glasmacher A, Molitor E, Hahn C, Bomba K, Ewig S, Leutner C, Wardelmann E, Schmidt-Wolf IG, Mezger J, Marklein G, Sauerbruch T (1998) Antifungal prophylaxis with itraconazole in neutropenic patients with acute leukaemia. Leukemia 12:1338–1343

    Article  CAS  PubMed  Google Scholar 

  36. Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ, et al. (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation [see comments]. N Engl J Med 326:845–851

    CAS  PubMed  Google Scholar 

  37. Gotzsche PC, Johansen HK (2002) Nystatin prophylaxis and treatment in severely immunodepressed patients (Cochrane Review). Cochrane Database Syst Rev (2):CD002033

    Google Scholar 

  38. Groll AH, Just-Nuebling G, Kurz M, Mueller C, Nowak-Goettl U, Schwabe D, Shah PM, Kornhuber B (1997) Fluconazole versus nystatin in the prevention of candida infections in children and adolescents undergoing remission induction or consolidation chemotherapy for cancer. J Antimicrob Chemother 40:855–862

    Article  CAS  PubMed  Google Scholar 

  39. Groll AH, Shah PM, Mentzel C, Schneider M, Just-Nuebling G, Huebner K (1996) Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 33:23–32

    CAS  PubMed  Google Scholar 

  40. Hann IM, Prentice HG, Corringham R, Blacklock HA, Keaney M, Shannon M, Noone P, Gascoigne E, Fox J, Boesen E, Szawatkowski M, Hoffbrand AV (1982) Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients. Lancet 1 (8276):826–829

    CAS  PubMed  Google Scholar 

  41. Hansen RM, Reinerio N, Sohnle PG, Abrams RA, Ritch PS, Libnoch JA, Anderson T (1987) Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study. Arch Intern Med 147:710–712

    Article  CAS  PubMed  Google Scholar 

  42. Harousseau JL, Dekker AW, Stamatoullas-Bastard A, Fassas A, Linkesch W, Gouveia J, De Bock R, Rovira M, Seifert WF, Joosen H, Peeters M, De Beule K (2000) Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B. Antimicrob Agents Chemother 44:1887–1893 [MEDLINE record in process]

    CAS  PubMed  Google Scholar 

  43. Hertenstein B, Kern WV, Schmeiser T, Stefanic M, Bunjes D, Wiesneth M, Novotny J, Heimpel H, Arnold R (1994) Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia [see comments]. Ann Hematol 68:21–26

    CAS  PubMed  Google Scholar 

  44. Huijgens PC, Simoons-Smit AM, van Loenen AC, Prooy E, van Tinteren H, Ossenkoppele GJ, Jonkhoff AR (1999) Fluconazole versus itraconazole for the prevention of fungal infections in haemato-oncology. J Clin Pathol 52:376–380

    CAS  PubMed  Google Scholar 

  45. Johansen HK, Gotzsche PC (2000) Amphotericin B lipid soluble formulations vs amphotericin B in cancer patients with neutropenia (Cochrane review). Cochrane Database Syst Rev (3):CD000969

    Google Scholar 

  46. Johansen HK, Gotzsche PC (2002) Amphotericin B versus fluconazole for controlling fungal infections in neutropenic cancer patients (Cochrane Review). Cochrane Database Syst Rev (2):CD000239

    Google Scholar 

  47. Jones PG, Kauffman CA, McAuliffe LS, Liepman MK, Bergman AG (1984) Efficacy of ketoconazole v nystatin in prevention of fungal infections in neutropenic patients. Arch Intern Med 144:549–551

    Article  CAS  PubMed  Google Scholar 

  48. Kaptan K, Ural AU, Cetin T, Avcu F, Beyan C, Yalcin A (2003) Itraconazole is not effective for the prophylaxis of fungal infections in patients with neutropenia. J Infect Chemother 9:40–45

    CAS  PubMed  Google Scholar 

  49. Karthaus M, Doellmann T, Klimasch T, Elser C, Rosenthal C, Ganser A, Heil G (2000) Intensive intravenous amphotericin B for prophylaxis of systemic fungal infections. Results of a prospective controlled pilot study in acute leukemia patients. Chemotherapy 46:293–302

    Article  CAS  PubMed  Google Scholar 

  50. Kelsey SM, Goldman JM, McCann S, Newland AC, Scarffe JH, Oppenheim BA, Mufti GJ (1999) Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in neutropenic patients: a randomised, double-blind, placebo- controlled study. Bone Marrow Transplant 23:163–168

    Article  CAS  PubMed  Google Scholar 

  51. Kern W, Behre G, Rudolf T, Kerkhoff A, Grote-Metke A, Eimermacher H, Kubica U, Wormann B, Buchner T, Hiddemann W (1998) Failure of fluconazole prophylaxis to reduce mortality or the requirement of systemic amphotericin B therapy during treatment for refractory acute myeloid leukemia: results of a prospective randomized phase III study. German AML Cooperative Group. Cancer 83:291–301

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  53. Lamy T, Bernard M, Courtois A, Jacquelinet C, Chevrier S, Dauriac C, Grulois I, Guiguen C, Le Prise PY (1998) Prophylactic use of itraconazole for the prevention of invasive pulmonary aspergillosis in high risk neutropenic patients. Leuk Lymphoma 30:163–174

    Google Scholar 

  54. Lass-Flörl C, Gunsilius E, Gastl G, Englisch M, Koch G, Ulmer H, Dierich MP, Petzer A (2003) Fungal colonization in neutropenic patients: a randomized study comparing itraconazole solution and amphotericin B solution. Ann Hematol DOI 10.1007/s00277–003–0666–5

  55. Laverdiere M, Rotstein C, Bow EJ, Roberts RS, Ioannou S, Carr D, Moghaddam N (2000) Impact of fluconazole prophylaxis on fungal colonization and infection rates in neutropenic patients. The Canadian Fluconazole Study. J Antimicrob Chemother 46:1001–1008

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  57. MacMillan ML, Goodman JL, DeFor TE, Weisdorf DJ (2002) Fluconazole to prevent yeast infections in bone marrow transplantation patients: a randomized trial of high versus reduced dose, and determination of the value of maintenance therapy. Am J Med 112:369–379

    Article  CAS  PubMed  Google Scholar 

  58. Marr KA, Carter RA, Boeckh M, Martin P, Corey L (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood

    Google Scholar 

  59. Marr KA, Crippa F, Leisenring W, Hoyle M, Balajee A, Musher B, Boeckh M, Corey L (2002) Itraconazole vs. Fluconazole for Antifungal Prophylaxis in Allogeneic HSCT Recipients: Results of a Randomized Trial. In: 44th Annual Meeting of the American Society of Hematology; Philadelphia, p 806

  60. Marr KA, Seidel K, Slavin MA, Bowden RA, Schoch HG, Flowers ME, Corey L, Boeckh M (2000) Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood 96:2055–2061

    Google Scholar 

  61. Martino P, Girmenia C, Micozzi A, De Bernardis F, Boccanera M, Cassone A, Donato V, Gastaldi R, Raccah R (1994) Prospective study of Candida colonization, use of empiric amphotericin B and development of invasive mycosis in neutropenic patients. Eur J Clin Microbiol Infect Dis 13:797–804

    CAS  PubMed  Google Scholar 

  62. Mattiuzzi GN, Estey E, Raad I, Giles F, Cortes J, Shen Y, Kontoyiannis D, Koller C, Munsell M, Beran M, Kantarjian H (2003) Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. Cancer 97:450–456

    Article  CAS  PubMed  Google Scholar 

  63. Mattiuzzi GN, Riehl T, Pierce SR, Rex JH, Cortes J, Giles F, Garcia-Manero G, Verstovsek S, Malekshamran K, Kantarjian HM, Estey EH (2002) Intravenous Itraconazole (ITRA) Versus Caspofungin (CASPO) for Prophylaxis of Invasive Fungal Infections (IFI) in Patients (PTS) with Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) Undergoing Induction Chemotherapy (IC). In: 44th Annual Meeting of the American Society of Hematology; Philadelphia, p 1286

  64. McNeil MM, Nash SL, Hajjeh RA, Phelan MA, Conn LA, Plikaytis BD, Warnock DW (2001) Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 33:641–647

    Article  CAS  PubMed  Google Scholar 

  65. Menichetti F, Del Favero A, Martino P, Bucaneve G, Micozzi A, D'Antonio D, Ricci P, Carotenuto M, Liso V, Nosari AM, et al. (1994) Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. The GIMEMA Infection Program. Ann Intern Med 120:913–918

    CAS  PubMed  Google Scholar 

  66. Menichetti F, Del Favero A, Martino P, Bucaneve G, Micozzi A, Girmenia C, Barbabietola G, Pagano L, Leoni P, Specchia G, Caiozzo A, Raimondi R, Mandelli F (1999) Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. GIMEMA Infection Program. Gruppo Italiano Malattie Ematologiche dell' Adulto. Clin Infect Dis 28:250–255

    CAS  PubMed  Google Scholar 

  67. Meunier F, Aoun M, Janssens M, Dekoster C, Paesmans M (1991) Chemoprophylaxis of fungal infections in granulocytopenic patients using fluconazole vs oral amphotericin B. Drug Invest 3:258–265

    Google Scholar 

  68. Morgenstern GR, Prentice AG, Prentice HG, Ropner JE, Schey SA, Warnock DW (1999) A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infections in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haematol 105:901–911

    CAS  PubMed  Google Scholar 

  69. Ninane J (1994) A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematological or oncological malignancies. Multicentre Study Group. Eur J Clin Microbiol Infect Dis 13:330–337

    CAS  PubMed  Google Scholar 

  70. Nucci M, Biasoli I, Akiti T, Silveira F, Solza C, Barreiros G, Spector N, Derossi A, Pulcheri W, Guarro J, Gene J, Barreiro MD, Goncalves RT (2000) A double-blind, randomized, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Clin Infect Dis 30:300–305

    Article  CAS  PubMed  Google Scholar 

  71. Oren I, Haddad N, Finkelstein R, Rowe JM (2001) Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters. Am J Hematol 66:257–262

    Article  CAS  PubMed  Google Scholar 

  72. Palmblad J, Lonnqvist B, Carlsson B, Grimfors G, Jarnmark M, Lerner R, Ljungman P, Nystrom-Rosander C, Petrini B, Oberg G (1992) Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias. J Intern Med 231:363–370

    CAS  PubMed  Google Scholar 

  73. Perfect JR, Klotman ME, Gilbert CC, Crawford DD, Rosner GL, Wright KA, Peters WP (1992) Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients. J Infect Dis 165:891–897

    CAS  PubMed  Google Scholar 

  74. Petraitiene R, Petraitis V, Groll AH, Sein T, Piscitelli S, Candelario M, Field-Ridley A, Avila N, Bacher J, Walsh TJ (2001) Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. Antimicrob Agents Chemother 45:857–869

    Article  CAS  PubMed  Google Scholar 

  75. Pfaffenbach B, Donhuijsen K, Pahnke J, Bug R, Adamek RJ, Wegener M, Ricken D (1994) [Systemic fungal infections in hematologic neoplasms. An autopsy study of 1,053 patients]. Med Klin 89:299–304

    CAS  PubMed  Google Scholar 

  76. Philpott-Howard JN, Wade JJ, Mufti GJ, Brammer KW, Ehninger G (1993) Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Multicentre Study Group. J Antimicrob Chemother 31:973–984

    CAS  PubMed  Google Scholar 

  77. Powles R, Mawhorter S, Williams T (1999) Liposomal Nystatin (Nyotran) Vs. Amphotericin B (Fungizone) in Empiric Treatment of Presumed Fungal Infection in Neutropenic Patients. In: Microbiology ASf, editor. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 1999; San Francisco, USA, p 14

  78. Rex JH, Sobel JD (2001) Prophylactic antifungal therapy in the intensive care unit. Clin Infect Dis 32:1191–1200

    CAS  PubMed  Google Scholar 

  79. Riley DK, Pavia AT, Beatty PG, Petersen FB, Spruance JL, Stokes R, Evans TG (1994) The prophylactic use of low-dose amphotericin B in bone marrow transplant patients. Am J Med 97:509–514

    CAS  PubMed  Google Scholar 

  80. Roberts J, Schock K, Marino S, Andriole VT (2000) Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis. Antimicrob Agents Chemother 44:3381–3388

    Article  CAS  PubMed  Google Scholar 

  81. Rotstein C, Bow EJ, Laverdiere M, Ioannou S, Carr D, Moghaddam N (1999) Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis 28:331–340

    CAS  PubMed  Google Scholar 

  82. Rousey SR, Russler S, Gottlieb M, Ash RC (1991) Low-dose amphotericin B prophylaxis against invasive Aspergillus infections in allogeneic marrow transplantation. Am J Med 91:484–492

    CAS  PubMed  Google Scholar 

  83. Rozenberg-Arska M, Dekker AW, Branger J, Verhoef J (1991) A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia. J Antimicrob Chemother 27:369–376

    CAS  PubMed  Google Scholar 

  84. Ryder NS, Leitner I (2001) Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species. Med Mycol 39:91–95

    CAS  PubMed  Google Scholar 

  85. Schaffner A, Schaffner M (1995) Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 172:1035–1041

    CAS  PubMed  Google Scholar 

  86. Schwartz S, Behre G, Heinemann V, Wandt H, Schilling E, Arning M, Trittin A, Kern WV, Boenisch O, Bosse D, Lenz K, Ludwig WD, Hiddemann W, Siegert W, Beyer J (1999) Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood 93:3654–3661

    PubMed  Google Scholar 

  87. Shepp DH, Klosterman A, Siegel MS, Meyers JD (1985) Comparative trial of ketoconazole and nystatin for prevention of fungal infection in neutropenic patients treated in a protective environment. J Infect Dis 152:1257–1263

    CAS  PubMed  Google Scholar 

  88. Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, Meyers JD, Bowden RA (1995) Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study. J Infect Dis 171:1545–1552

    CAS  PubMed  Google Scholar 

  89. Takatsuka H, Takemoto Y, Okamoto T, Fujimori Y, Tamura S, Wada H, Okada M, Kanamaru A, Kakishita E (1999) Fluconazole versus amphotericin B for the prevention of fungal infection in neutropenic patients with hematologic malignancy. Drugs Exp Clin Res 25:193–200

    CAS  PubMed  Google Scholar 

  90. Thunnissen PL, Sizoo W, Hendriks WD (1991) Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients. Neth J Med 39:84–91

    Google Scholar 

  91. Timmers GJ, Zweegman S, Simoons-Smit AM, van Loenen AC, Touw D, Huijgens PC (2000) Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial. Bone Marrow Transplant 25:879–884

    Article  CAS  PubMed  Google Scholar 

  92. Todeschini G, Murari C, Bonesi R, Pizzolo G, Amaddi G, Ambrosetti A, Ceru S, Piacentini I, Martini N, Montresor P, et al. (1993) Oral itraconazole plus nasal amphotericin B for prophylaxis of invasive aspergillosis in patients with hematological malignancies. Eur J Clin Microbiol Infect Dis 12:614–618

    CAS  PubMed  Google Scholar 

  93. Tollemar J, Hockerstedt K, Ericzon BG, Sundberg B, Ringden O (1994) Fungal prophylaxis with AmBisome in liver and bone marrow transplant recipients: results of two randomized double-blind studies. Transplant Proc 26:1833

    CAS  PubMed  Google Scholar 

  94. Tollemar J, Ringden O, Andersson S, Sundberg B, Ljungman P, Sparrelid E, Tyden G (1993) Prophylactic use of liposomal amphotericin B (AmBisome) against fungal infections: a randomized trial in bone marrow transplant recipients. Transplant Proc 25 (1 Pt 2):1495–1497

    CAS  PubMed  Google Scholar 

  95. Tollemar J, Ringden O, Andersson S, Sundberg B, Ljungman P, Tyden G (1993) Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients. Bone Marrow Transplant 12:577–582

    CAS  PubMed  Google Scholar 

  96. Tricot G, Joosten E, Boogaerts MA, Vande Pitte J, Cauwenbergh G (1987) Ketoconazole vs. itraconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results of two nonrandomized studies. Rev Infect Dis 9 (Suppl 1):S94–S99

    Google Scholar 

  97. van Burik JA, Ratanatharathorn V, Lipton J, Miller C, Bunin N, Walsh TJ (2002) Randomized, Double-Blind Trial of Micafungin (MI) versus Fluconazole (FL) for Prophylaxis of Invasive Fungal Infections in Patients (pts) undergoing Hematopoietic Stem Cell Transplant (HSCT), NIAID/BAMSG Protocol 46. In: 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002, p 401

  98. Viscoli C, Paesmans M, Sanz M, Castagnola E, Klastersky J, Martino P, Glauser M (2001) Association between antifungal prophylaxis and rate of documented bacteremia in febrile neutropenic cancer patients. Clin Infect Dis 32:1532–1537

    Article  CAS  PubMed  Google Scholar 

  99. Vogler WR, Malcom LG, Winton EF (1987) A randomized trial comparing ketoconazole and nystatin prophylactic therapy in neutropenic patients. Cancer Invest 5:267–273

    CAS  PubMed  Google Scholar 

  100. Vreugdenhil G, Van Dijke BJ, Donnelly JP, Novakova IR, Raemaekers JM, Hoogkamp-Korstanje MA, Koster M, de Pauw BE (1993) Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematologic malignancies and intensive chemotherapy. A double blind, placebo controlled study. Leuk Lymphoma 11:353–358

    Google Scholar 

  101. Winston DJ, Chandrasekar PH, Lazarus HM, Goodman JL, Silber JL, Horowitz H, Shadduck RK, Rosenfeld CS, Ho WG, Islam MZ, et al. (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial [see comments]. Ann Intern Med 118:495–503

    CAS  PubMed  Google Scholar 

  102. Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, Leitz GJ, Territo MC (2003) Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann Intern Med 138:705–713

    CAS  PubMed  Google Scholar 

  103. Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Leitz G, Territo MC (2001) Long-term antifungal prophylaxis in allogeneic bone marrow transplant patients: a multicenter, randomized trial of intravenous/oral itraconazole versus intravenous/oral fluconazole [abstract 2002]. Blood 96:479a

  104. Wolff SN, Fay J, Stevens D, Herzig RH, Pohlman B, Bolwell B, Lynch J, Ericson S, Freytes CO, LeMaistre F, Collins R, Pineiro L, Greer J, Stein R, Goodman SA, Dummer S (2000) Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group. Bone Marrow Transplant 25:853–859

    CAS  PubMed  Google Scholar 

  105. Yamac K, Senol E, Haznedar R (1995) Prophylactic use of fluconazole in neutropenic cancer patients. Postgrad Med J 71:284–286

    CAS  PubMed  Google Scholar 

  106. Young GA, Bosly A, Gibbs DL, Durrant S (1999) A double-blind comparison of fluconazole and nystatin in the prevention of candidiasis in patients with leukaemia. Antifungal Prophylaxis Study Group. Eur J Cancer 35:1208–1213

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Klinik I für Innere Medizin, Klinikum der Universität zu Köln, 50931, Köln, Germany

    Oliver A. Cornely & Michal Sieniawski

  2. Medizinische Klinik III, Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    Angelika Böhme

  3. Medizinische Klinik, Universitätsklinikum Mannheim, Wiesbadener Strasse 7-11, 68305, Mannheim, Germany

    Dieter Buchheidt

  4. Universitätsklinik Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53105, Bonn, Germany

    Axel Glasmacher

  5. Klinik für Hämatologie und Onkologie, Universitätsklinik Rostock, Ernst-Heydemann-Strasse 6, 18057, Rostock, Germany

    Christoph Kahl

  6. Medizinische Klinik II, Evangelisches Johannes-Krankenhaus, Schildescher Strasse 99, 33611, Bielefeld, Germany

    Meinolf Karthaus

  7. Universitätsklinikum Freiburg, Innere Medizin II/Infektiologie Medizinische Klinik und Poliklinik, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Winfried Kern

  8. Hämatologie und Onkologie—Transplantationszentrum, Klinik und Poliklinik für Innere Medizin C, Sauerbruchstrasse, Diagnostikzentrum, 17487, Greifswald, Germany

    William Krüger

  9. Medizinische Klinik m.S. Hämatologie und Onkologie, Universitätsklinikum Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Georg Maschmeyer

  10. Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie/Onkologie, Universitätsklinikum Münster, 48129, Münster, Germany

    Jörg Ritter

  11. Medizinische Universitätspoliklinik Heidelberg, Hospitalstrasse 3, 69115, Heidelberg, Germany

    Hans J. Salwender

  12. II. Medizinische Klinik, Klinikum Augsburg, 86009, Augsburg, Germany

    Michael Sandherr

  13. Medizinische Klinik 3, Klinikum der Ludwig Maximilian-Universität, 81377, München-Grosshadern, Germany

    Xaver Schiel

  14. Zentrum Innere Medizin, Abteilung für Hämatologie/Onkologie, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    Silke Schüttrumpf

  15. Medizinische Klinik A, KMT-Zentrum, Uniklinik Münster, 48149 , Münster, Germany

    Gerda Silling

  16. III. Medizinische Klinik und Poliklinik, Klinikum der Johannes Gutenberg-Universität, Langenbeckstrasse 1, 55101, Mainz, Germany

    Andrew J. Ullmann

  17. Klinik für Innere Medizin IV, Martin-Luther-Universität, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany

    Hans-Heinrich Wolf

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  1. Oliver A. Cornely
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  2. Angelika Böhme
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  18. Hans-Heinrich Wolf
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Correspondence to Oliver A. Cornely.

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Cornely, O.A., Böhme, A., Buchheidt, D. et al. Prophylaxis of invasive fungal infections in patients with hematological malignancies and solid tumors. Ann Hematol 82 (Suppl 2), S186–S200 (2003). https://doi.org/10.1007/s00277-003-0773-3

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