Blood Reviews
Volume 20, Issue 5 , Pages 267-287 , September 2006

New strategies of antifungal therapy in hematopoietic stem cell transplant recipients and patients with hematological malignancies

  • Helen L. Leather

      Affiliations

    • Shands at the University of Florida, P.O. Box 100316, 1600 SW Archer Road, Room 4179.1, Gainesville, FL 32610-0316, United States
    • Corresponding Author InformationCorresponding author. Tel.: +352 265 0680x45839; fax: +352 265 0189.
  • ,
  • John R. Wingard

      Affiliations

    • Division of Hematology/Oncology; College of Medicine, Deputy Director Gainesville Campus of the University of Florida Shands Cancer Center, P.O. Box 100277, 1600 SW Archer Road, R4-165, Gainesville, FL 32610-0277, United States
    • Tel.: +352 273 8021; fax: +352 392 8530.

References 

  1. EORTC. Empiric antifungal therapy in febrile granulocytopenic patients. EORTC International Antimicrobial Therapy Cooperative Group. Am J Med 1989;86:668–672.
  2. Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med. 1982;72:101–111
  3. Kern W, Behre G, Rudolf T, et al. 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 trial. Cancer. 1998;83:291–301
  4. Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326:845–851
  5. Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation – a prospective, randomized, double-blind study. J Infect Dis. 1995;171:1545–1552
  6. Marr KA, Seidel K, Slavin MA, et al. 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. 2000;96:2055–2061
  7. MacMillan ML, Goodman JL, DeFor TE, Weisdorf DJ. 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. 2002;112:369–379
  8. Wolff SN, Fay J, Stevens D, et al. 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. 2000;25:853–859
  9. Koh LP, Kurup A, Goh YT, Fook-Chong SM, Tan PH. Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation. Am J Hematol. 2002;71:260–267
  10. Winston DJ, Chandrasekar PH, Lazarus HM, et al. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multi-center trial. Ann Intern Med. 1993;118:495–503
  11. Vardakas KZ, Michalopoulos A, Falagas ME. Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomized-controlled trials. Br J Haem. 2005;131:22–28
  12. Rotstein C, Bow EJ, Laverdiere M, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis. 1999;28:331–340
  13. Perfect JR, Klotman ME, Gilbert CC, Crawford DD, Rosner GL, Wright KA, et al. Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients. J Infect Dis. 1992;165:891–897
  14. Rousey SR, Russler S, Gottlieb M, Ash RC. Low-dose amphotericin B prophylaxis against invasive Aspergillus infections in allogeneic marrow transplantation. Am J Med. 1991;91:484–491
  15. Karthaus M, Doellmann T, Klimasch T, et al. Intensive intravenous amphotericin B prophylaxis of systemic fungal infections: results of a prospective controlled pilot study in acute leukemia patients. Chemotherapy. 2000;46:293–302
  16. Riley DK, Pavia AT, Beatty PG, Petersen FB, Spruance JL, Stokes R, et al. The prophylactic use of low-dose amphotericin B in bone marrow transplant patients. Am J med. 1994;76:509–514
  17. Mattiuzzi GN, Estey E, Raad I, et al. 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. 2003;97:450–456
  18. Tollemar J, Ringden O, Andersson S, Sundberg B, Ljungman P, Tyden G. Randomized double-blind study of liposomal amphotericin B (Ambisome) prophylaxis of invasive fungal infections in bone marrow transplant recipients. Bone Marrow Transplant. 1993;12:577–582
  19. Kelsey SM, Goldman JM, McCann S, Newland AC, Scarffe JH, Oppenheim BA, et al. Liposomal amphotericin (Ambisome) in the prophylaxis of fungal infections in neutropenic patients: a randomized, double-blind, placebo-controlled study. Bone Marrow Transplant. 1999;23:163–168
  20. Brincker H. Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study. Acta Med Scand. 1978;204:123–128
  21. Wingard JR, Vaughan WP, Braine HG, Merz WG, Saral R. Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole. Am J Med. 1987;83:1103–1110
  22. Wiley JM, Smith N, Leventhal BG, et al. Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. J Clin Oncol. 1990;8:280–286
  23. Palmblad J, Lonnqvist B, Carlsson B, et al. Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias. J Intern Med. 1992;231:363–370
  24. Benhamou E, Hartmann O, Nogues C, Maraninchi D, Valteau D, Lemerle J. Does ketoconazole prevent fungal infection in children treated with high dose chemotherapy and bone marrow transplantation? Results of a randomized placebo-controlled trial. Bone Marrow Transplant. 1991;7:127–131
  25. Hansen RM, Reinerio N, Sohnle PG, Abrams RA, Ritch PS, Libnoch JA, et al. Ketoconazole in the prevention of candidiasis in patients with cancer. A prospective, randomized, controlled, double-blind study. Arch Intern Med. 1987;147:710–712
  26. Estey E, Maksymiuk A, Smith T, et al. Infection prophylaxis in acute leukemia. Comparative effectiveness of sulfamethoxazole and trimethoprim, ketoconazole, and a combination of the two. Arch Intern Med. 1984;144:1562–1568
  27. Marr KA, Crippa F, Leisenring W, Crippa F, Slattery JT, Corey L, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004;103:1527–1533
  28. Winston DJ, Maziarz RT, Chandrasekar PH, et al. 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. 2003;138:705–713
  29. Menichetti D, del Favero A, Martino P, et al. Itraconazole oral solution as prophylaxis for fungal infections in neutropenic patients with hematologic malignancies: a randomized, placebo-controlled, double-blind, multicenter trial. Clin Infect Dis. 1999;28:250–255
  30. Morgenstern GR, Prentice AG, Prentice HG, Ropner JE, Schey SA, Warnock DW. A randomized controlled trial of itraconazole versus fluconazole for the prevention of fungal infection in patients with haematological malignancies. U.K. Multicentre Antifungal Prophylaxis Study Group. Br J Haem. 1999;105:901–911
  31. Harousseau J, Dekker A, Stamatoullas-Bastard A, et al. Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematologic malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B. Antimicrob Agents Chemother. 2000;44:1887–1893
  32. Huijgens PC, Simoons-Smit AM, van Loenen AC, Prooy E, van Tinteren H, Ossenkppele GJ, et al. Fluconazole versus itraconazole for the prevention of fungal infections in hemato-oncology. J Clin Pathol. 1999;52:376–380
  33. Nucci M, Biasoli I, Akiti T, et al. A double-blind, placebo-controlled trial of itraconazole capsules as antifungal prophylaxis for neutropenic patients. Clin Infect Dis. 2000;30:300–305
  34. Boogaerts M, Maertens J, van Hood A, et al. Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients. J Antimicrob Chemother. 2001;48:97–103
  35. Ullman. Posaconazole (POS) vs Fluconazole (FLU) for Prophylaxis of Invasive Fungal Infections (IFIs) in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Recipients With Graft-Versus-Host Disease (GVHD): Results of a Multicenter Trial. In: Program and Proceedings of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; December 15 – 18th, 2005; Washington DC. Abstract 2111.
  36. Van Burik JH, Ratanatharathorn V, Stepan DE, et al. Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis. 2004;39:1407–1416
  37. Wingard JR. Design issues in a prospective randomized double-blinded trial of prophylaxis with fluconazole versus voriconazole after allogeneic hematopoietic cell transplantation. Clin Infect Dis. 2004;39(Suppl 4):S176–S180
  38. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of the Center for Disease Control and Prevention, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2000;6:659–734.
  39. Safdar , van Rhee F, Henslee-Downey JP, Singhal S, Mehta J. Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome. Bone Marrow Transplant. 2001;28:873–878
  40. Kanda Y, Yamamoto R, Chizuka A, et al. Prophylactic action of oral fluconazole against fungal infection in neutropenic patients: a meta-analysis of 16 randomized, controlled trials. Cancer. 2002;89:1611–1625
  41. Bow EJ, Laverdiere M, Lussier N, Rotstein C, Cheany MS, Ioannou S. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta-analysis of randomized-controlled clinical trials. Cancer. 2002;94:3230–3246
  42. Wingard JR, Mertz WG, Rinaldi MG, Johnson TR, Karp JE, Saral R. Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med. 1991;325:1274–1277
  43. Persons DA, Laughlin M, Tanner D, Perfect J, Gockerman JP, Hathorn JW. Fluconazole and Candida krusei fungemia. N Engl J Med. 1991;325:1315
  44. Wingard JR, Mertz WG, Rinaldi MG, Miller CB, Karp JE, Saral R. Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother. 1993;37:1847–1849
  45. Glasmacher A, Prentice A, Gorschluter M, Engelhart S, Hahn C, Djulbegovic B, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol. 2003;21:4615–4626
  46. Schwartz S, Behre G, Heinemann V, et al. Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood. 1999;93:3654–3661
  47. Behre GF, Schwartz S, Lenz K, et al. Aerosol amphotericin B inhalations for prevention of invasive pulmonary aspergillosis in neutropenic cancer patients. Ann Hematol. 1995;71:287–291
  48. Drew RH, Dodds AE, Benjamin DK, Davis D, Palmer SM, Perfect JR. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation. 2004;77:232–237
  49. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;357:408–415
  50. Kullberg BJ, Pappas P, Ruhnke M, et al. Voriconazole compared with a strategy of amphotericin B followed by fluconazole for treatment of candidemia in non-neutropenic patients. Clin Microbiol Infect. 2004;10(Suppl 3):41;[Abstract O245]
  51. Husain S, Zaldonis DB, Kwak EJ, McCurry KR. Role of voriconazole prophylaxis for the prevention of invasive aspergillosis (IA) at six months in lung transplant recipients. J Heart Lung Transplant. 2004;23:S110;[Abstract 205]
  52. Van Well GT, van Groeningen I, Debets-Ossenkopp YJ, van Furth AM, Zawaan CM. Zygomycete infection following voriconazole prophylaxis. Lancet Infect Dis. 2005;5:594
  53. Kontoyiannis DP, Lionakis MS, Lweis RE, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. Clin Infect Dis. 2005;191:1350–1360
  54. Imhof A, Balajee SA, Fredericks DN, Englund JA, Marr KA. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis. 2004;39:743–746
  55. Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med. 2004;350:950–952
  56. Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, et al. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis. 2004;39:584–587
  57. Vigouroux S, Morin O, Moreau P, et al. Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required. Clin Infect Dis. 2005;40:e35–e37
  58. Kobayashi K, Kami M, Murashige N, Kishi Y, Fujisaki G, Mitamura T. Breakthrough zygomycosis during voriconazole treatment for invasive aspergillosis. Haematologica. 2004;89:ECR42
  59. Oren I. Breakthrough zygomycosis during empirical voriconazole therapy in febrile patients with neutropenia. Clin Infect Dis. 2005;40:770–771
  60. Mattner F, Weissbrodt H, Strueber M. Two case reports: fatal Absidia corymbifera pulmonary tract infections in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient. Scand J Infect Dis. 2004;36:312–314
  61. Marr KA, Carter RA, Crippa F, Wald , Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909–917
  62. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KI. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2002;30:851–856
  63. Park BJ, Kontoyiannis DP, Pappas PG, et al. Comparison of Zygomycosis and Fusariosis to invasive aspergillosis (IA) among transplant recipients reporting to TRANSNET. In: Program and Proceedings of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 30 – November 2, 2004; Washington DC. Abstract M-666.
  64. Bennett JE, Powers J, Walsh T, et al. Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis. 2003;36(Suppl 3):S117–S122
  65. Viscoli C, Castagnola E, van Lint MT, et al. Fluconazole versus amphotericin B as empiric antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicenter, prospective and randomized clinical trial. Eur J Cancer. 1996;32A:814–820
  66. Malik IA, Moid I, Aziz Z, Khan S, Suleman M. A randomized comparison of fluconazole with amphotericin B as empirical antifungal agents in cancer patients with prolonged fever and neutropenia. Am J Med. 1998;105:478–483
  67. Winston DJ, Hathorn JW, Schuster MG, Schiller GJ, Territo MC. A multicenter, randomized trial of fluconazole versus amphotericin B for empirical antifungal therapy in neutropenic patients with cancer. Am J Med. 2000;108:282–289
  68. Prentice HG, Hann IM, Herbrecht R, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997;98:711–718
  69. White MH, Bowden RA, Sandler ES, et al. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion versus amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis. 1998;27:296–302
  70. Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999;340:764–771
  71. Boogaerts M, Winston DJ, Bow EJ, et al. Intravenous and oral itraconazole versus amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy: a randomized, controlled trial. Am J Med. 2001;135:412–422
  72. Wingard JR, White MH, Anaissie R, Raffalli J, Goodman J, Arrieta A, et al. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. Clin Infect Dis. 2000;31:1155–1163
  73. Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002;346:225–234
  74. Walsh TJ, Teppler HA, Donowitz GR, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004;351:1391–1402
  75. Wingard JR. Empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis. 2004;39:S38–S43
  76. Maertens JA, Theunissen K, Boogaerts MA. In:  Wingard JR,  Anaissie EJ editor. Fungal Infections in the Immunocompromised Patient. Boca Raton: Taylor and Francis; 2005;p. 621–635
  77. Greene R. The radiological spectrum of pulmonary aspergillosis. Med Mycol. 2005;43(Suppl 1):LS147–LS154
  78. Caillot D, Couaillier JF, Bernard A, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computer tomography scans in patients with neutropenia. J Clin Oncol. 2001;19:253–259
  79. Maertens J, Verhaegen J, Lagrou K, van Eldere J, Boogaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation patients: a prospective validation. Blood. 2001;97:1604–1610
  80. Maertens J, van Eldere J, Verhaegen J, Verbeken E, Verschalkelen J, Boogaerts M. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant patients. J Infect Dis. 2002;186:1297–1306
  81. Sulahian A, Boutboul F, Ribaud P, Leblanc T, Lacroix C, Derouin F. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Cancer. 2001;91:311–318
  82. Boutboul F, Alberti C, Leblanc T, Sulahian A, Gluckman E, Derouin F, et al. Invasive aspergillosis in allogeneic stem cell transplant recipients: increasing antigenemia is associated with progressive disease. Clin Infect Dis. 2002;34:939–943
  83. Rovira M, Jiminez M, De La Bellacasa JP, et al. Detection of Aspergillus galactomannan by enzyme immunoabsorbent assay in recipients of allogeneic hematopoietic stem cell transplantation: a prospective study. Transplantation. 2004;77:1260–1264
  84. Kawazu M, Kanda Y, Nannya Y, et al. Prospective comparison of the diagnostic potential of real-time PCR, double-sandwich enzyme-linked immunosorbent assay for galactomannan, and a (13)-β-D-glucan test in weekly screening for invasive aspergillosis in patients with haematological disorders. J Clin Microbiol. 2004;42:2733–2741
  85. Herbrecht R, Letscher-Bru V, Oprea C, et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol. 2002;20:1898–1906
  86. Pinel C, Fricker-Hidalgo H, Lebeau , Garban F, Hamidfar R, Ambroise-Thomas P, et al. Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the platelia test for diagnosing invasive aspergillosis. J Clin Microbiol. 2003;41:2184–2186
  87. Maertens J, Theunissen K, Verbeken E, Lagrou K, Verhaegen J, Boogaerts M, et al. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol. 2004;126:852–860
  88. Hebart H, Loffler J, Meisner C, et al. Early detection of Aspergillus infection after allogeneic stem cell transplantation by polymerase chain reaction screening. J Infect Dis. 2000;181:1713–1719
  89. Lass-Florl C, Aigner J, Gunsilius B, et al. Screening for Aspergillus spp. using polymerase chain reaction of whole blood samples from patients with haematological malignancies. Br J Haematol. 2001;113:180–184
  90. Hebart H, Loffler J, Reitzke H, et al. Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropenia. Br J Haematol. 2000;111:635–640
  91. Odabasi Z, Mattiuzzi G, Estey E, et al. β-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004;39:199–205
  92. Ostrosky-Zeichneer L, Alexander B, Kett DH, et al. Multicenter clinical evaluation of the (13) β-D-Glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis. 2005;41:654–659
  93. Pazos C, Ponton J, Del Palacio A. Contribution of (13)-β-D-Glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol. 2005;43:299–305
  94. Kami M, Fukui T, Ogawa S, et al. Use of real-time OCR on blood samples for diagnosis of invasive aspergillosis. Clin Infect Dis. 2001;33:1504–1512
  95. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. Clin Infect Dis. 2004;190:641–649
  96. Weisser M, Rausch C, Droll A, et al. Galactomannan does not preceded major signs on a pulmonary computerized tomography scan suggestive of invasive aspergillosis in patients with hematological malignancies. Clin Infect Dis. 2005;41:1143–1149
  97. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis. 2005;41:1242–1250
  98. Anaissie EJ, Vartivarian SE, Abi-Said D, et al. Fluconazole versus amphotericin B in the treatment of hematogenous Candidiasis: a matched cohort study. Am J Med. 1996;101:170–176
  99. Phillips P, Shafran S, Garber G, et al. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis. 1997;16:337–345
  100. Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N Engl J Med. 1994;331:1325–1330
  101. Rex JH, Pappas PG, Karchmer AW, et al. 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 non-neutropenic subjects. Clin Infect Dis. 2003;36:1221–1228
  102. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020–2029
  103. Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, et al. Practice guidelines for the treatment of Candidiasis. Clin Infect Dis. 2004;38:161–189
  104. Bowden R, Chandresekar P, White MH, et al. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2002;15:359–366
  105. Smith J, Safdar N, Knasinski V, Andes DR. Voriconazole (V) therapeutic drug monitoring (TDM): Indications, levels, and outcomes at a single tertiary care hospital. In: Program and Proceedings of the 42nd Annual Meeting of the Infectious Disease Society of America; September 30 – October 3rd, 2004; Boson MA. Abstract 629.
  106. Trifilio S, Ortiz R, Pennick G, et al. Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2005;35:509–513
  107. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef M. The influence of inadequate antimicrobial treatment of bloodstream infections on patient’s outcomes in the ICU setting. Chest. 2000;118:146–155
  108. Greene R. ECCMID 2003 Abstract.
  109. Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis. 2000;30:710–718
  110. Arikan S, Lozano-Chiu M, Paetznick V, Rex JH. In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother. 2002;46:245–247
  111. Dannaoui E, Lortholary O, Dromer F. In vitro evaluation of double and triple combinations of antifungal drugs against Aspergillus fumigatus and Aspergillus terreus. Antimicrob Agents Chemother. 2004;48:970–978
  112. Kirkpatrick WR, Perea S, Coco BJ, Patterson TF. Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother. 2002;46:2564–2568
  113. Manavathu EK, Alangaden GJ, Chandrasekar PH. Differential activity of triazoles in two-drug combinations with the echinocandin caspofungin against Aspergillus fumigatus. J Antimicrob Chemother. 2003;51:1423–1425
  114. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother. 2002;46:3039–3041
  115. Luque JC, Clemons KV, Stevens DA. Efficacy of micafungin alone or in combination against systemic murine aspergillosis. Antimicrob Agents Chemother. 2003;47:1452–1455
  116. MacCallum DM, Whyte JA, Odds FC. Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis. Antimicrob Agents Chemother. 2005;49:3697–3701
  117. Graybill JR, Bocanegra R, Gonzalez GM, Najvar LK. Combination antifungal therapy of murine aspergillosis: liposomal amphotericin B and micafungin. J Antimicrob Chemother. 2003;52:656–662
  118. Chandresaker PH, Cutright JL, Manavathu EK. Efficacy of voriconazole plus amphotericin B or micafungin in a guinea-pig model of invasive pulmonary aspergillosis. Clin Microbiol Infect. 2004;10:925–928
  119. Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002;34:7–14
  120. Kontoyiannis DP, Hachem R, Lewis re , et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003;98:292–299
  121. Aliff TB, Maslak PG, Jurcic JG, Heaney ML, Cathcart KN, Sepkowitz KA, et al. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer. 2003;97:1025–1032
  122. Kontoyiannis DP, Boktour M, Hanna H, Hachem R, Raad II. Itraconazole added to a lipid formulation of amphotericin B does not improve outcome of primary treatment of invasive aspergillosis. Cancer. 2005;103:2334–2337
  123. Marr KA, Boeckh M, Carter RA, Kim HQW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39:797–802

PII: S0268-960X(06)00016-6

doi: 10.1016/j.blre.2006.03.001

Blood Reviews
Volume 20, Issue 5 , Pages 267-287 , September 2006