Seminars in Hematology
Volume 46, Issue 3 , Pages 212-229 , July 2009

Recent Advances in Antifungal Prevention and Treatment

  • Andreas H. Groll

      Affiliations

    • Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital Muenster, Muenster, Germany
    • Corresponding Author InformationAddress correspondence to Andreas H. Groll, MD, Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, Children's University Hospital, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany
  • ,
  • Athanasios Tragiannidis

      Affiliations

    • Second Department of Pediatrics, Aristotle University, AHEPA Hospital, Thessaloniki, Greece

References 

  1. Segal BH, Bow EJ, Menichetti F. Fungal infections in nontransplant patients with hematologic malignancies. Infect Dis Clin North Am. 2002;16:935–964
  2. Groll AH, Walsh TJ. Recent developments in epidemiology and management of invasive fungal infections. In:  Lazarus HM,  Laughlin MJ editor. Allogeneic stem cell transplantation (Clinical research and practice). Totowa, NJ: Humana Press; 2003;p. 191–213
  3. Wingard JR. New approaches to invasive fungal infections in acute leukemia and hematopoietic stem cell transplant patients. Best Pract Res Clin Haematol. 2007;20:99–107
  4. Richardson M, Lass-Flörl C. Changing epidemiology of systemic fungal infections. Clin Microbiol Infect. 2008;14(Suppl 4):5–24
  5. Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative targets for antifungal drug development. Adv Pharmacol. 1998;44:343–500
  6. Groll AH, Glasmacher A, Just-Nuebling G, Maschmeyer G, Walsh TJ. Clinical pharmacology of antifungal compounds. Infect Dis Clin North Am. 2003;17:159–191
  7. Walsh TJ, Chanock SJ. Diagnosis of invasive fungal infections: advances in nonculture systems. Curr Clin Top Infect Dis. 1998;18:101–153
  8. Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev. 2002;15:465–484
  9. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Infect Dis. 2005;5:609–622
  10. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts: approved standard. CLSI document M27-A3 3rd ed.. Wayne, PA: CLSI; 2008;
  11. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. Approved standard. NCCLS document M38-A Wayne, PA: National Committee for Clinical Laboratory Standards; 2002;
  12. Rex JR, Walsh TJ, Nettleman M, et al. Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses. Clin Infect Dis. 2001;35:95–106
  13. Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, et al. Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases 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
  14. Bennett JE, Powers J, Walsh T, Viscoli C, de Pauw B, Dismukes W, 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
  15. Menichetti F. How to improve the design of trials of antifungal prophylaxis among neutropenic adults with acute leukemia. Clin Infect Dis. 2004;39(Suppl 4):S181–S184
  16. Powers JH. Considerations in clinical trials of combination antifungal therapy. Clin Infect Dis. 2004;39(Suppl 4):S228–S235
  17. Anaissie EJ. Trial design for mold-active agents: time to break the mold-aspergillosis in neutropenic adults. Clin Infect Dis. 2007;44:1298–1306
  18. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–1821
  19. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Infectious Diseases Society of America Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–360
  20. Pappas PG, Kauffman CA, Andes D, Benjamin DK, Calandra TF, Edwards JE, et al. Infectious Diseases Society of America Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:503–535
  21. Böhme A, Ruhnke M, Buchheidt D, Cornely OA, Einsele H, Enzensberger R, et al. Treatment of invasive fungal infections in cancer patients—recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol. 2009;88:97–110
  22. Cornely OA, Böhme A, Buchheidt D, Einsele H, Heinz WJ, Karthaus M, et al. 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
  23. Chiou CC, Walsh TJ, Groll AH. Clinical pharmacology of antifungal agents in pediatric patients. Expert Opin Pharmacother. 2007;8:2465–2489
  24. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Morb Mortal Wkly Rep. 2000;49(RR-10):1–95
  25. Humphreys H. Positive-pressure isolation and the prevention of invasive aspergillosis (What is the evidence?). J Hosp Infect. 2004;56:93–100
  26. Walsh TJ, Dixon DM. Nosocomial aspergillosis: environmental micro-biology, hospital epidemiology, diagnosis and treatment. Eur J Epidemiol. 1989;5:131–142
  27. Goodman DJ, Winston JL, 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
  28. Slavin MA, Osborne E, 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
  29. 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
  30. Winston DJ, Maziarz RT, Chandrasekar PH, Lazarus HM, Goldman M, Blumer JL, 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
  31. Marr KA, Crippa F, Leisenring W, Hoyle M, Boeckh M, Balajee SA, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood. 2004;103:1527–1533
  32. Marr KA, Leisenring W, Crippa F, Slattery JT, Corey L, Boeckh M, et al. Cyclophosphamide metabolism is affected by azole antifungals. Blood. 2004;103:1557–1559
  33. Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, et al. Results of a randomized, double-blind trial of fluconazole (FLU) vs. voriconazole (VORI) for the prevention of invasive fungal infections (IFI) in 600 allogeneic blood and marrow transplant (BMT) patients. [abstract] Blood. 2007;110:235
  34. van Burik JA, Ratanatharathorn V, Stepan DE, Miller CB, Lipton JH, Vesole DH, 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
  35. 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
  36. El-Cheikh J, Faucher C, Fürst S, Duran S, Berger P, Vey N, et al. High-dose weekly liposomal amphotericin B antifungal prophylaxis following reduced-intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant. 2007;39:301–306
  37. Cordonnier C, Mohty M, Faucher C, Pautas C, Robin M, Vey N, et al. Safety of a weekly high dose of liposomal amphotericin B for prophylaxis of invasive fungal infection in immunocompromised patients: PROPHYSOME Study. Int J Antimicrob Agents. 2008;31:135–141
  38. Menichetti F, 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
  39. 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
  40. Ullmann AJ, Cornely OA. Antifungal prophylaxis for invasive mycoses in high risk patients. Curr Opin Infect Dis. 2006;19:571–576
  41. Glasmacher A, Prentice A, Gorschlüter 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
  42. Vardakas KZ, Michalopoulos A, Falagas ME. Fluconazole versus itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomised-controlled trials. Br J Haematol. 2005;131:22–28
  43. 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
  44. Penack O, Schwartz S, Martus P, Reinwald M, Schmidt-Hieber M, Thiel E, et al. Low-dose liposomal amphotericin B in the prevention of invasive fungal infections in patients with prolonged neutropenia: results from a randomized, single-center trial. Ann Oncol. 2006;17:1306–1312
  45. 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;46:1401–1408
  46. Marr KA, Seidel K, White TC, Bowden RA. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis. 2000;181:309–316
  47. Trifilio SM, Bennett CL, Yarnold PR, McKoy JM, Parada J, Mehta J, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 2007;39:425–429
  48. Snelders E, van der Lee HA, Kuijpers J, Rijs AJ, Varga J, Samson RA, et al. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 2008;5:e219
  49. Baixench MT, Aoun N, Desnos-Ollivier M, Garcia-Hermoso D, Bretagne S, Ramires S, et al. Acquired resistance to echinocandins in Candida albicans: case report and review. J Antimicrob Chemother. 2007;59:1076–1083
  50. Garcia-Effron G, Kontoyiannis DP, Lewis RE, Perlin DS. Caspofungin-resistant Candida tropicalis strains causing breakthrough fungemia in patients at high risk for hematologic malignancies. Antimicrob Agents Chemother. 2008;52:4181–4183
  51. Kahn JN, Garcia-Effron G, Hsu MJ, Park S, Marr KA, Perlin DS. Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase. Antimicrob Agents Chemother. 2007;51:1876–1878
  52. 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
  53. European Organization for Research and Treatment of Cancer. Empiric antifungal therapy in febrile granulocytopenic patients (EORTC International Antimicrobial Therapy Cooperative Group). Am J Med. 1989;86:668–672
  54. Prentice HG, Hann IM, Herbrecht R, et al. A randomized comparison of liposomal versus conventional amphotericin B for treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997;98:711–718
  55. 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
  56. Boogaerts M, Winston DJ, Bow EJ, et al. Intravenous and oral itraconazole versus intravenous amphotericin B as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. Ann Intern Med. 2001;135:412–422
  57. Winston DJ, Hathorn JW, Schuster MG, et al. A multicentre, randomized trial of fluconazole vs. amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med. 2000;108:282–289
  58. Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, 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
  59. Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, 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
  60. Wingard JR, White MH, Anaissie E, 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 (L Amph/ABLC Collaborative Study Group). Clin Infect Dis. 2000;31:1155–1163
  61. Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, et al. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis. 2006;43:25–31
  62. Berenguer J, Buck M, Witebsky F, Stock F, Pizzo PA, Walsh TJ. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis (Disseminated versus single-organ infection). Diagn Microbiol Infect Dis. 1993;17:103–109
  63. Pastakia B, Shawker TH, Thaler M, O'Leary T, Pizzo PA. Hepatosplenic candidiasis: wheels within wheels. Radiology. 1988;166:417–421
  64. Semelka RC, Shoenut JP, Greenberg HM, Bow EJ. Detection of acute and treated lesions of hepatosplenic candidiasis: comparison of dynamic contrast-enhanced CT and MR imaging. J Magn Reson Imaging. 1992;2:341–345
  65. White PL, Archer AE, Barnes RA. Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections. J Clin Microbiol. 2005;43:2181–2187
  66. Spiess B, Seifarth W, Hummel M, Frank O, Fabarius A, Zheng C, et al. DNA microarray-based detection and identification of fungal pathogens in clinical samples from neutropenic patients. J Clin Microbiol. 2007;45:3743–3753
  67. Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukaemia and myelodysplastic syndrome. Clin Infect Dis. 2004;39:199–205
  68. Senn L, Robinson JO, Schmidt S, Knaup M, Asahi N, Satomura S, et al. 1,3-Beta-D-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clin Infect Dis. 2008;46:878–885
  69. Parkins MD, Sabuda DM, Elsayed S, Laupland KB. Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections. J Antimicrob Chemother. 2007;60:613–618
  70. Pittet D, Monod M, Suter PM, Frenk E, Auckenthaler R. Candida colonization and subsequent infections in critically ill surgical patients. Ann Surg. 1994;220:751–758
  71. León C, Ruiz-Santana S, Saavedra P, Almirante B, Nolla-Salas J, Alvarez-Lerma F, et al. A bedside scoring system (“Candida score”) for early antifungal treatment in nonneutropenic critically ill patients with Candida colonization. Crit Care Med. 2006;34:730–737
  72. Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998;26:781–805
  73. Schwartz S, Ruhnke M, Ribaud P, Corey L, Driscoll T, Cornely OA, et al. Improved outcome in central nervous system aspergillosis, using voriconazole treatment. Blood. 2005;106:2641–2645
  74. Sutton DA, Sanche SE, Revankar SG, Fothergill AW, Rinaldi MG. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Microbiol. 1999;37:2343–2345
  75. Steinbach WJ, Benjamin DK, Kontoyiannis DP, Perfect JR, Lutsar I, Marr KA, et al. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin Infect Dis. 2004;39:192–198
  76. Greene RE. Advances and prospects of diagnostic imaging of invasive fungal infections. Curr Fungal Infect Rep. 2007;1:146–152
  77. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, 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
  78. Yeghen T, Kibbler CC, Prentice HG, et al. Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution. Clin Infect Dis. 2000;31:859–868
  79. Burgos A, Zaoutis TE, Dvorak CC, Hoffman JA, Knapp KM, Nania JJ, et al. Pediatric invasive aspergillosis: a multicenter retrospective analysis of 139 contemporary cases. Pediatrics. 2008;121:e1286–e1294
  80. Buchheidt D, Baust C, Skladny H, Baldus M, Bräuninger S, Hehlmann R. Clinical evaluation of a polymerase chain reaction assay to detect Aspergillus species in bronchoalveolar lavage samples of neutropenic patients. Br J Haematol. 2002;116:803–811
  81. Musher B, Fredricks D, Leisenring W, Balajee SA, Smith C, Marr KA. Aspergillus galactomannan enzyme immunoassay and quantitative PCR for diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid. J Clin Microbiol. 2004;42:5517–5522
  82. Lass-Flörl C, Resch G, Nachbaur D, Mayr A, Gastl G, Auberger J, et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin Infect Dis. 2007;45:e101–e104
  83. Rickerts V, Mousset S, Lambrecht E, Tintelnot K, Schwerdtfeger R, Presterl E, et al. Comparison of histopathological analysis, culture, and polymerase chain reaction assays to detect invasive mold infections from biopsy specimens. Clin Infect Dis. 2007;44:1078–1083
  84. Hebart H, Löffler J, Meisner C, Serey F, Schmidt D, Böhme A, et al. Early detection of aspergillus infection after allogeneic stem cell transplantation by polymerase chain reaction screening. J Infect Dis. 2000;181:1713–1719
  85. Segal BH, Almyroudis NG, Battiwalla M, Herbrecht R, Perfect JR, Walsh TJ, et al. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin Infect Dis. 2007;44:402–409
  86. Hebart H, Klingspor L, Klingebiel T, Loeffler J, Tollemar J, Ljungman P, et al. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after Allo-SCT. Bone Marrow Transplant. 2008;Dec 15. [Epub ahead of print]
  87. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E. Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect. 2004;10(Suppl 1):48–66
  88. Reboli AC, Rotstein C, Pappas PG, Chapman SW, Kett DH, Kumar D, et al. Anidulafungin Study Group Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007;356:2472–2482
  89. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347:2020–2029
  90. Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, et al. Micafungin Invasive Candidiasis Working Group Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007;369:1519–1527
  91. Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–893
  92. Graybill JR, Najvar LK, Luther MF, Fothergill AW. Treatment of murine disseminated candidiasis with L-743,872. Antimicrob Agents Chemother. 1997;41:1775–1777
  93. Groll AH, Mickiene D, Petraitiene R, Petraitis V, Lyman CA, Bacher JS, et al. Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling. Antimicrob Agents Chemother. 2001;45:2845–2855
  94. Petraitis V, Petraitiene R, Groll AH, Roussillon K, Hemmings M, Lyman CA, et al. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother. 2002;46:1857–1869
  95. Anaissie EJ, Darouiche RO, Abi-Said D, et al. Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis. 1996;23:964–972
  96. Uzun O, Ascioglu S, Anaissie EJ, Rex JH. Risk factors and predictors of outcome in patients with cancer and breakthrough candidemia. Clin Infect Dis. 2001;32:1713–1717
  97. Trifilio S, Singhal S, Williams S, Frankfurt O, Gordon L, Evens A, et al. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant. 2007;40:451–456
  98. Kullberg BJ, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Rex JH, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole forcandidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005;366:1435–1442
  99. Perfect JR, Marr KA, Walsh TJ, Greenberg RN, DuPont B, de la Torre-Cisneros J, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003;36:1122–1131
  100. Walsh TJ, Hiemenz JW, Seibel NL, et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis. 1998;26:1383–1396
  101. Ito JI, Hooshmand-Rad R. Treatment of Candida infections with amphotericin B lipid complex. Clin Infect Dis. 2005;40(Suppl 6):S384–S391
  102. Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, et al. Infectious Diseases Society of America Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38:161–189
  103. Groll AH, Giri N, Petraitis V, Petraitiene R, Candelario M, Bacher JS, et al. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J Infect Dis. 2000;182:274–282
  104. Legrand F, Lecuit M, Dupont B, Bellaton E, Huerre M, Rohrlich PS, et al. Adjuvant corticosteroid therapy for chronic disseminated candidiasis. Clin Infect Dis. 2008;46:696–702
  105. Bjerke JW, Meyers JD, Bowden RA. Hepatosplenic candidiasis—a contraindication to marrow transplantation?. Blood. 1994;84:2811–2814
  106. Walsh TJ, Whitcomb PO, Revankar SG, Pizzo PA. Successful treatment of hepatosplenic candidiasis through repeated cycles of chemotherapy and neutropenia. Cancer. 1995;76:2357–2362
  107. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–415
  108. Cornely OA, Maertens J, Bresnik M, Ebrahimi R, Ullmann AJ, Bouza E, et al. AmBiLoad Trial Study Group Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007;44:1289–1297
  109. Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis. 2002;34:563–571
  110. Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, et al. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J. 2002;21:240–248
  111. Chandrasekar PH, Ito JI. Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2005;40(Suppl 6):S392–S400
  112. White MH, Anaissie EJ, Kusne S, Wingard JR, Hiemenz JW, Cantor A, et al. Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis. Clin Infect Dis. 1997;24:635–642
  113. Bowden R, Chandrasekar P, White MH, Li X, Pietrelli L, Gurwith M, 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;35:359–366
  114. Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39:1563–1571
  115. Denning DW, Lee JY, Hostetler JS, et al. (1994) NIAID Mycoses Study Group multicenter trial of oral itraconazole therapy for invasive aspergillosis. Am J Med. 1994;97:135–144
  116. Stevens DA, Lee JY. Analysis of compassionate use itraconazole therapy for invasive aspergillosis by the NIAID Mycoses Study Group criteria. Arch Intern Med. 1997;157:1857–1862
  117. Caillot D, Bassaris H, McGeer A, Arthur C, Prentice HG, Seifert W, et al. 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. 2001;33:e83–e90
  118. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44:2–12
  119. Ringden O, Meunier F, Tollemar J, et al. Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients. J Antimicrob Chemother. 1991;28(Suppl B):73–82
  120. Maertens J, Glasmacher A, Herbrecht R, Thiebaut A, Cordonnier C, Segal BH, et al. Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer. 2006;107:2888–2897
  121. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39:797–802
  122. Caillot D, Thiébaut A, Herbrecht R, de Botton S, Pigneux A, Bernard F, et al. Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial). Cancer. 2007;110:2740–2746
  123. Groll AH, Kolve H. Antifungal agents: in vitro susceptibility testing, pharmacodynamics, and prospects for combination therapy. Eur J Clin Microbiol Infect Dis. 2004;23:256–270
  124. Mouas H, Lutsar I, Dupont B, Fain O, Herbrecht R, Lescure FX, et al. Voriconazole for invasive bone aspergillosis: a worldwide experience of 20 cases. Clin Infect Dis. 2005;40:1141–1147
  125. Walsh TJ, Garrett K, Feurerstein E, Girton M, Allende M, Bacher J, et al. Therapeutic monitoring of experimental invasive pulmonary aspergillosis by ultrafast computerized tomography, a novel, noninvasive method for measuring responses to antifungal therapy. Antimicrob Agents Chemother. 1995;39:1065–1069
  126. Caillot D, Couaillier JF, Bernard A, Casasnovas O, Denning DW, Mannone L, et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J Clin Oncol. 2001;19:253–259
  127. Smith J, Safdar N, Knasinski V, Simmons W, Bhavnani SM, Ambrose PG, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006;50:1570–1572
  128. Trifilio S, Pennick G, Pi J, Zook J, Golf M, Kaniecki K, et al. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer. 2007;109:1532–1535
  129. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008;46:201–211
  130. Courtney R, Pai S, Laughlin M, Lim J, Batra V. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob Agents Chemother. 2003;47:2788–2795
  131. Safdar A. Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections. Bone Marrow Transplant. 2006;38:327–337
  132. Anaissie EJ. Diagnosis and therapy of fungal infection in patients with leukemia—new drugs and immunotherapy. Best Pract Res Clin Haematol. 2008;21:683–690
  133. Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol. 1997;15:139–147
  134. Wong K, Waters CM, Walesby RK. Surgical management of invasive pulmonary aspergillosis in immunocompromised patients. Eur J Cardiothorac Surg. 1992;6:138–142
  135. Danner BC, Didilis V, Dörge H, Mikroulis D, Bougioukas G, Schöndube FA. Surgical treatment of pulmonary aspergillosis/mycosis in immunocompromised patients. Interact Cardiovasc Thorac Surg. 2008;7:771–776
  136. Martino R, Lopez R, Sureda A, et al. Risk of reactivation of a recent invasive fungal infection in patients with hematological malignancies undergoing further intensive chemoradiotherapy (A single center experience and review of the literature). Hematologica. 1997;82:297–304
  137. Offner F, Cordonnier C, Ljungman P, et al. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis. 1998;26:1098–1103
  138. Sipsas NV, Kontoyiannis DP. Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin Infect Dis. 2006;42:1584–1591
  139. Allinson K, Kolve H, Gumbinger HG, Vormoor HJ, Ehlert K, Groll AH. Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients. J Antimicrob Chemother. 2008;61:734–742
  140. Raad I, Chapman S, Bradsher R, Morrison V, Goldman M, Graybill J. Posaconazole salvage therapy for invasive fungal infections. [abstract M-669] In: Abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology; 2004;
  141. Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Heath CH, Lutsar I, et al. Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients. Antimicrob Agents Chemother. 2008;52:1743–1750
  142. Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006;50:126–133
  143. van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42:e61–e65
  144. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634–653
  145. 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
  146. Dromer F, Bernede-Bauduin C, Guillemot D, Lortholary O French Cryptococcosis Study Group. Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PLoS ONE. 2008;3:e2870
  147. Lewis RE, Kontoyiannis DP. Rationale for combinations antifungal therapy. Pharmacotherapy. 2001;21:149S–164S
  148. Sugar AM. Antifungal combination therapy. Curr Opin Invest Drugs. 2001;2:1364–1365
  149. Wheat LJ. Combination therapy for aspergillosis: is it needed, and which combination?. J Infect Dis. 2003;187:1831–1833
  150. Wirk B, Wingard JR. Combination antifungal therapy: from bench to bedside. Curr Fungal Infect Rep. 2008;2:43–48
  151. Medoff G, Comfort M, Kobayashi GS. Synergistic action of amphotericin B and 5-fluorocytosine against yeast-like organisms. Proc Soc Exp Biol Med. 1971;138:571–574
  152. Bennett JE, Dismukes WE, Haywood M, Duma R, Medoff G. A comparison of amphotericin B alone and in combination with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med. 1979;301:126–131
  153. Van der Horst CM, Saag MS, Cloud GA, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997;337:15–21
  154. Schaffner A, Bohler A. Amphotericin B refractory aspergillosis after itraconazole: evidence for significant antagonism. Mycoses. 1993;36:421–424
  155. Sugar AM, Hitchcock CA, Troke PF, Picard M. Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. Antimicrob Agents Chemother. 1995;39:598–601
  156. Sugar AM, Liu XP. Interactions of itraconazole with amphotericin B in the treatment of murine invasive candidiasis. J Infect Dis. 1998;177:1660–1663
  157. Meletiadis J, Petraitis V, Petraitiene R, Lin P, Stergiopoulou T, Kelaher AM, et al. Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation. J Infect Dis. 2006;194:1008–1018
  158. Rex JH, Pappas PG, Karchmer AW, Sobel J, Edwards JE, Hadley S, et al. National Institute of Allergy and Infectious Diseases Mycoses Study Group 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. 2003;36:1221–1228
  159. Sionov E, Mendlovic S, Segal E. Efficacy of amphotericin B or amphotericin B-intralipid in combination with caspofungin against experimental aspergillosis. J Infect. 2006;53:131–139
  160. 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
  161. Petraitis V, Petraitiene R, Sarafandi AA, Kelaher AM, Lyman CA, Casler HE, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis. 2003;187:1834–1843
  162. 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
  163. Kontoyiannis DP, Hachem R, Lewis RE, Rivero GA, Torres HA, Thornby J, 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
  164. Denning DW, Marr KA, Lau WM, Facklam DP, Ratanatharathorn V, Becker C, et al. Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis. J Infect. 2006;53:337–349
  165. Groll AH, Young C, Schwerdtfeger R, Tischer J, Heinz W, Cornely O, et al. Randomized comparison of safety, tolerance and pharmacokinetics of caspofungin, liposomal amphotericin b and the combination of both in allogeneic hematopoietic stem cell recipients (CASLAMB trial). [abstract M-2178] In: Abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology; 2008;p. 677
  166. Ibrahim AS, Gebremariam T, Fu Y, Edwards JE, Spellberg B. Combination echinocandin-polyene treatment of murine mucormycosis. Antimicrob Agents Chemother. 2008;52:1556–1558
  167. Reed C, Bryant R, Ibrahim AS, Edwards J, Filler SG, Goldberg R, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47:364–371
  168. Roilides E, Lyman CA, Panagopoulou P, Chanock S. Immunomodulation of invasive fungal infections. Infect Dis Clin North Am. 2003;17:193–219
  169. Ribaud P, Chastang C, Latgé JP, Baffroy-Lafitte L, Parquet N, Devergie A, et al. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis. 1999;28:322–330
  170. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44:531–540
  171. Berenguer J, Allende MC, Lee JW, Garrett K, Lyman C, Ali NM, et al. Pathogenesis of pulmonary aspergillosis (Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression). Am J Respir Crit Care Med. 1995;152:1079–1086
  172. Segal BH, Kwon-Chung J, Walsh TJ, Klein BS, Battiwalla M, Almyroudis NG, et al. Immunotherapy for fungal infections. Clin Infect Dis. 2006;42:507–515
  173. Safdar A, Rodriguez GH, Lichtiger B, Dickey BF, Kontoyiannis DP, Freireich EJ, et al. Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer. 2006;106:2664–2671
  174. Chanock SJ, Gorlin JB. Granulocyte transfusions (Time for a second look). Infect Dis Clin North Am. 1996;10:327–343
  175. Safdar A, Hanna HA, Boktour M, Kontoyiannis DP, Hachem R, Lichtiger B, et al. Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections. Cancer. 2004;101:2859–2865
  176. Mousset S, Hermann S, Klein SA, Bialleck H, Duchscherer M, Bomke B, et al. Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Ann Hematol. 2005;84:734–741
  177. Pachl J, Svoboda P, Jacobs F, Vandewoude K, van der Hoven B, Spronk P, et al. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis. 2006;42:1404–1413
  178. Spellberg BJ, Collins M, Avanesian V, Gomez M, Edwards JE, Cogle C, et al. Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts. J Leukoc Biol. 2007;81:632–641
  179. Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L, Carotti A, et al. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood. 2005;106:4397–4406
  180. Beck O, Topp MS, Koehl U, Roilides E, Simitsopoulou M, Hanisch M, et al. Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus. Blood. 2006;107:2562–2569

PII: S0037-1963(09)00058-4

doi: 10.1053/j.seminhematol.2009.03.003

Seminars in Hematology
Volume 46, Issue 3 , Pages 212-229 , July 2009