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Current and Future Therapeutic Options in the Management of Invasive Aspergillosis

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Abstract

The past decade has witnessed significant progress in the management of invasive aspergillosis. Potent, relatively non-toxic antifungal drugs, data on early chest CT scanning and the availability of a non-invasive diagnostic test (serum galactomannan) are the key advances; among these, the contribution of the recently available drugs is the most significant. Safer and earlier intervention resulting in reduced mortality and improved outcome is being demonstrated. Newer strategies enable clinicians to provide drug therapy in a highly targeted manner, such that empirical use of antifungal drugs may decline. Voriconazole has become the drug of choice for primary therapy, while posaconazole shows promise as a prophylactic drug. Echinocandins are effective for salvage therapy and are under evaluation for primary therapy. Preliminary data for efficacy of combination therapy with a mould-active azole plus an echinocandin are of promise and clinical trials are under way. Reports of emergence of less-susceptible Aspergillus spp. during azole therapy are of concern and close monitoring is needed. Remarkably, the era of polyenes appears to be nearing the end in the therapy of invasive aspergillosis. The promise of newer classes of drugs, immune-modulating therapies and vaccines are exciting future additions to the arsenal against invasive aspergillosis.

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  1. The use of trade names is for identification purposes only and does not imply endorsement.

References

  1. Mandell GL, Bennett JE, Dolin R. Principles & practice of infectious diseases. 6th ed. Vol 2. New York: Churchill Livingstone, 2006: 257

    Google Scholar 

  2. McNeil MM, Nash SL, Hajjeyh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States: 1980–1997. Clin Infect Dis 2001; 33: 641–7

    Article  PubMed  CAS  Google Scholar 

  3. Reichenberger F, Habicht JM, Gratwohl A, et al. Diagnosis and treatment of invasive pulmonary aspergillosis in neutropenicpatients. Eur Respir J 2002; 19: 743–55

    Article  PubMed  CAS  Google Scholar 

  4. Ribaud P, Chastang C, Latge J-P, et al. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis 1999; 28: 322–30

    Article  PubMed  CAS  Google Scholar 

  5. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev 2005; 18: 44–69

    Article  PubMed  CAS  Google Scholar 

  6. Gubbins PO, Anaissie E. Overview of antifungal agents. Inf Dis Special Edition 2007; 10: 58–65

    Google Scholar 

  7. Enoch DA, Ludlam HA, Brown NM. Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol. 2006; 55: 809–18

    Article  PubMed  CAS  Google Scholar 

  8. Hope WW, Walsh TJ, Denning DW. Laboratory diagnosis of invasive aspergillosis. Lancet Inf Dis 2005; 5: 609–22

    Article  CAS  Google Scholar 

  9. Stynen D, Goris A, Sarfati J, et al. A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis. J Clin Microbiol 1995; 33: 497–500

    PubMed  CAS  Google Scholar 

  10. Miyazaki T, Kohno S, Mitsutake K, et al. Plasma (1,3)-β-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis. J Clin Microbiol 1995; 33: 3115–8

    PubMed  CAS  Google Scholar 

  11. Sulahian A, Touratier S, Ribaud P. False-positive test for Aspergillus antigenemia related to concomitant administration of piperacillin and tazobactam. N Engl J Med 2003; 349: 2366–7

    Article  PubMed  CAS  Google Scholar 

  12. 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 (1->3)-ta-D-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders. J Clin Microbiol 2004; 42: 2733–41

    Article  PubMed  CAS  Google Scholar 

  13. Caillot D, Couaillier JF, Bernard A, 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: 253–9

    PubMed  CAS  Google Scholar 

  14. Denning DW, Marr KA, Lau WM, et al. Micafungin (FK463), alone or in combination with other systemic antifungal agents for the treatment of acute invasive aspergillosis. J Infect 2006; 53: 337–49

    Article  PubMed  Google Scholar 

  15. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev 1999; 12: 40–79

    PubMed  CAS  Google Scholar 

  16. Patterson TF, Boucher HW, Herbrecht R, et al. European Organization for Research and Treatment of Cancer (EORTC), Invasive Fungal Infections Group (IFIG) and the Pfizer Global Aspergillus Study Group. Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin Infect Dis 2005; 41: 1448–52

    CAS  Google Scholar 

  17. Candoni A, Mestroni R, Damiani D, et al. Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematological malignancies. Eur J Hematology 2005; 75: 227–33

    Article  CAS  Google Scholar 

  18. Herbrecht R, Denning DW, Patterson, et al. Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group. Voriconazole versus Amphotericin B for Primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408–15

    CAS  Google Scholar 

  19. Cornely OA, Maertens J, Bresnik M. Liposomal amphotericin B (L-AMB) as initial therapy for invasive filamentous fungal infections (IFFI): a randomized prospective trial of a high loading dose regimen versus standard dosing (Ambiload trial) [abstract]. Blood 2005; 106: 3222

    Google Scholar 

  20. Ito JI, Chandrasekar PH, Hooshmand-R Rad R. Effectiveness of amphotericin B lipid complex (ABLC) treatment in allogeneic hematopoietic stem cell transplant (HSCT) recipients with invasive aspergillosis (IA). Bone Marrow Transplant 2005; 36: 873–7

    Article  PubMed  CAS  Google Scholar 

  21. Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med 2006; 173: 707–17

    Article  PubMed  CAS  Google Scholar 

  22. 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: 450–6

    CAS  Google Scholar 

  23. Glasmacher A, Prentice A, Gorschluter M, et al. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematological malignancies: evidence from a meta analysis of 3,597 patients. J Clin Oncol 2003; 21: 4615–26

    Article  PubMed  CAS  Google Scholar 

  24. Winston DJ, Maziarz RT, Chandrasekar PH, et al. Intravenous and oral itraconazole versus intravenous and oral fluconazole for long-term antifungal prophylaxis in allogenic hematopoietic stem cell transplant recipients: a multicenter randomized trial. Ann Intern Med 2003; 138: 705–13

    PubMed  CAS  Google Scholar 

  25. Marr KA, Crippa F, Leisenring W, et al. Itraconazole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood 2004; 103: 1527–33

    Article  PubMed  CAS  Google Scholar 

  26. Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356: 348–59

    Article  PubMed  CAS  Google Scholar 

  27. Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007; 356: 335–47

    Article  PubMed  CAS  Google Scholar 

  28. Mattiuzzi GN, Alvarado G, Giles FJ, et al. Open-label randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematological malignancies. Antimicrob Agents Chemother 2006; 50: 143–7

    Article  PubMed  CAS  Google Scholar 

  29. Van Burik J, Ratanatharathorn V, Stefan DE, et al. 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). Clin Infect Dis 2004; 39: 1407–16

    Article  PubMed  Google Scholar 

  30. Martino R, Parody R, Fukuda T, et al. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 2006; 108: 2928–36

    Article  PubMed  CAS  Google Scholar 

  31. Pizzo PA, Robichaud KJ, Gill FA, et al. Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 1982; 72: 101–11

    Article  PubMed  CAS  Google Scholar 

  32. EORTC International Antimicrobial Therapy Cooperative Group. Empiric antifungal therapy in febrile granulocytopenic patients. Am J Med 1989; 86: 668–72

    Article  Google Scholar 

  33. Klastersky J. Antifungal therapy in patients with fever and neutropenia: more rational and less empirical? N Engl J Med 2004; 351: 1445–7

    Article  PubMed  CAS  Google Scholar 

  34. Malik IA, Moid I, Aziz Z. A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia. Am J Med 1998; 105: 478–83

    Article  PubMed  CAS  Google Scholar 

  35. Viscoli C, Castagnola E, Van Lint MT, et al. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer 1996; 32: 814–20

    Article  Google Scholar 

  36. 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: 764–71

    Article  PubMed  CAS  Google Scholar 

  37. Winston DJ, Hathorn JW, Schuster MG, et al. A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med 2000; 108: 282–9

    Article  PubMed  CAS  Google Scholar 

  38. Boogaerts M, Winston DJ, Bow EJ, et al. Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy: a randomized, controlled trial. Ann Intern Med 2001; 135: 412–22

    PubMed  CAS  Google Scholar 

  39. 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: 225–34

    Article  PubMed  CAS  Google Scholar 

  40. Johnson JR, Ullmann AJ, Heussel CP, et al. Voriconazole versus liposomal amphotericin B for empirical antifungal therapy. N Engl J Med 2002; 346: 1745–7

    Article  PubMed  Google Scholar 

  41. Walsh TJ, Lee J, Dismukes WE, et al. Decisions about voriconazole versus liposomal amphotericin B. N Engl J Med 2002; 346: 1499

    Article  PubMed  Google Scholar 

  42. Walsh TJ, Teppler H, 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: 1391–402

    Article  PubMed  CAS  Google Scholar 

  43. Kontoyiannis DP, Lewis RE, Tattevin P, et al. Caspofungin versus liposomal amphotericin B for empirical therapy. N Engl J Med 2005; 352: 410–4

    Article  PubMed  CAS  Google Scholar 

  44. Gotzsche PPC, Johansen HK. Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or no treatment in patients with cancer complicated by neutropenia. BMJ 1997; 314: 1238–44

    Article  PubMed  CAS  Google Scholar 

  45. Stephanie PM, Gottardi M, Zanetti F, et al. Pre-emptive antifungal therapy among neutropenic patients. Clin Infect Dis 2006; 42: 1507–8

    Article  Google Scholar 

  46. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography-based pre-emptive antifungal therapy in neutropenic patients at high risk for invasive fungal infections; a prospective feasibility study. Clin Infect Dis 2005; 41: 1242–50

    Article  PubMed  CAS  Google Scholar 

  47. Lin MT, Lu HC, Chen WL. Improving efficacy of antifungal therapy by polymerase chain reaction based strategy among febrile patients with neutropenia and cancer. Clin Infect Dis 2001; 33: 1621–7

    Article  PubMed  CAS  Google Scholar 

  48. Greene RE, Schlamm HT, Oestmann JW, et al. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 2007; 44: 373–9

    Article  PubMed  Google Scholar 

  49. Greene R. Radiology of fungal infections in the immunocompromised patient. In: Wingard JR, Anaisse EJ, editors. Fungal infections in the immunocompromised patient. Boca Raton (FL): Taylor & Francis Group LLC, 2005: 407–8(B)

    Google Scholar 

  50. Weisser M, Rausch C, Droll A, et al. Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies. Clin Infect Dis 2005; 41: 1143–9

    Article  PubMed  CAS  Google Scholar 

  51. Viscoli C. Combination therapy for invasive aspergillosis. Clin Infect Dis 2004; 39: 803–5

    Article  PubMed  CAS  Google Scholar 

  52. Singh N, Limaye AP, Forrest G, et al. Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation 2006; 81: 320–6

    Article  PubMed  CAS  Google Scholar 

  53. Kirkpatrick WR, Perea S, Coco BJ. Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002; 46: 2564–8

    Article  PubMed  CAS  Google Scholar 

  54. Petraitis V, Petraitiene R, Sarafandi AA, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis 2003; 187: 1834–43

    Article  PubMed  CAS  Google Scholar 

  55. Marr KA, Boeckh M, Carter RA, et al. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004; 39: 797–802

    Article  PubMed  CAS  Google Scholar 

  56. Caillot D, Thiebaut A, Herbrecht R, et al. Liposomal amphotericin B in combination with caspofungin versus liposomal amphotericin B high dose regimen for the treatment of invasive aspergillosis in immunocompromised patients: randomized pilot study (Combistrat trial) [abstract no. P-004]. Focus on Fungal Infections 16; 2006 Mar 8–10; Las Vegas (NV)

  57. Ratnatharathorn V, Flynn P, Van Burik JA, et al. Micafungin in combination with systemic antifungal agents in the treatment of refractory aspergillosis (RA) in bone marrow transplant (BMT) patients [abstract no. 2472]. 44th Annual Meeting of the American Society of Hematology; 2002 Dec 6–10; Philadelphia (PA)

  58. Maertens J, Raad I, Petrikkos G, et al. For the Caspofungin Salvage Aspergillosis Study Group. 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: 1563–71

    Article  PubMed  CAS  Google Scholar 

  59. Walsh TJ, Raad I, Patterson TF, 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 Jan 1; 44: 2–12

    Article  PubMed  CAS  Google Scholar 

  60. Perfect J, González-Ruiz A, Lutsar I, et al. Voriconazole (VORI) for the treatment of resistant and rare fungal pathogens [abstract no. 303]. 38th Annual Meeting of the Infectious Diseases Society of America; 2000 Sep 7–10; New Orleans (LA)

  61. Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging or refractory fungal infections. Clin Infect Dis 2003; 36: 1122–31

    Article  PubMed  CAS  Google Scholar 

  62. Denning DW, Stevens DA. Antifungal and surgical treatment of invasive aspergillosis: review of 2121 published cases. Rev Infect Dis 1990; 12: 1147–201

    Article  PubMed  CAS  Google Scholar 

  63. Reichenberger F, Habicht J, Kaim A, et al. Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases. Am J Resp Crit Care Med 1998; 158: 885–90

    PubMed  CAS  Google Scholar 

  64. Habicht JM, Matt P, Passweg JR, et al. Invasive pulmonary fungal infection in hematological patients: is resection effective? Hematology J 2001; 2: 250–6

    Article  CAS  Google Scholar 

  65. Safdar A. Strategies to enhance immune function in hematopoietic transplantation patients with invasive fungal infections. Bone Marrow Transplant 2006; 38: 327–37

    Article  PubMed  CAS  Google Scholar 

  66. Chiou CC, Groll AH, Walsh TJ. New drugs and novel targets for the treatment of invasive fungal infections in patients with cancer. Oncologist 2000; 5: 120–35

    Article  PubMed  CAS  Google Scholar 

  67. Steinbach WJ, Steens DA. Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis. Clin Infect Dis 2003; 37 Suppl. 3: S157–87

    Article  PubMed  CAS  Google Scholar 

  68. Hata K, Kimura J, Miki H, et al. Efficiency of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis and cryptococcosis. Antimicrob Agents Chemother 1996; 40: 2243–7

    PubMed  CAS  Google Scholar 

  69. Offner F, Krcmery V, Boogaerts M, et al. Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B. Antimicrob Agents Chemother 2004; 48: 4808–12

    Article  PubMed  CAS  Google Scholar 

  70. Walsh TJ, Giri N. Pradimicins: a novel class of broad-spectrum antifungal compounds. Eur J Clin Microbiol Infect Dis 1997; 16: 93–7

    Article  PubMed  CAS  Google Scholar 

  71. Ganesan LT, Manavathu EK, Cutright JL, et al. In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. Clin Microbiol Infect 2004; 10: 961–6

    Article  PubMed  CAS  Google Scholar 

  72. Herreros E, Martinez CM, Almela MJ, et al. Sordarins: in vitro activities of new antifungal derivatives against pathogenic yeasts, Pneumocystis carini and filamentous fungi. Antimicrob Agents Chemother 1998; 42(11): 2863–9

    PubMed  CAS  Google Scholar 

  73. Cenci E, Mencacci A, Fe d’Ostiani C, et al. Cytokine and T-helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis 1998; 178: 1750–60

    Article  PubMed  CAS  Google Scholar 

  74. Cenci E, Mencacci A, Del Sero G, et al. Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I response. J Infect Dis 1999; 180: 1957–68

    Article  PubMed  CAS  Google Scholar 

  75. Hamilton JA, Whitty GA, Royston AKM, et al. Interleukin-4 suppresses granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor levels in stimulated monocytes. Immunology 1992; 76: 566–71

    PubMed  CAS  Google Scholar 

  76. Safdar A, Rodriguez G, Ohmagari N, et al. The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation. Cancer 2005; 103: 731–9

    Article  PubMed  CAS  Google Scholar 

  77. Casadevall A, Pirofski L. Adjunctive immune therapy for invasive fungal infections. Clin Infect Dis 2001; 33: 1048–56

    Article  PubMed  CAS  Google Scholar 

  78. Nemunaitis J, Buckner CD, Dorsey KS, et al. Retrospective analysis of infectious diseases in patients who received recombinant human granulocyte-macrophage colony-stimulating factor versus patients not receiving a cytokine who underwent autologous bone marrow transplantation for treatment of lymphoid cancer. Am J Clin Oncol 1998; 21: 341–6

    Article  PubMed  CAS  Google Scholar 

  79. Brummer E, Maqbool A, Stevens DA. In vivo GM-CSF prevents dexamethasone suppression of killing of Aspergillus fumigatus conidia by bronchoalveolar macrophages. J Leukoc Biol 2001; 70: 868–72

    PubMed  CAS  Google Scholar 

  80. Rowe JM, Andersen JW, Maza J, et al. A randomized, placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood 1995; 86: 457–62

    PubMed  CAS  Google Scholar 

  81. Ito JI, Lyons JM, Hong TB, et al. Vaccinations with recombinant variants of Aspergillus fumigatus allergen Asp f 3 protect mice against invasive aspergillosis. Infect Immun. 2006; 74: 5075–84

    Article  PubMed  CAS  Google Scholar 

  82. Feldmesser M. Prospects of vaccines for invasive aspergillosis. Med Mycol 2005; 43: 571–87

    Article  PubMed  CAS  Google Scholar 

  83. Denikus N, Orfaniotou F, Wulf G, et al. Fungal antigens expressed during invasive aspergillosis. Infect Immun 2005; 73(8): 4704–13

    Article  PubMed  CAS  Google Scholar 

  84. Sheppard DC, Edwards Jr JE. Development of a vaccine for invasive aspergillosis. Clin Infect Dis 2004; 38: 1137–8

    Article  PubMed  Google Scholar 

  85. Stevens DA. Vaccinate against aspergillosis! A call to arms of the immune system. Clin Infect Dis 2004; 38: 1131–6

    Article  PubMed  Google Scholar 

  86. Hebart H, Bollinger C, Fisch P, et al. Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies. Blood 2002; 100: 4521–8

    Article  PubMed  CAS  Google Scholar 

  87. Ito JI, Lyons JM. Vaccination of corticosteroid immunosuppressed mice against invasive pulmonary aspergillosis. J Infect Dis 2002; 186: 869–71

    Article  PubMed  Google Scholar 

  88. Bozza S, Gaziano R, Lipford GB, et al. Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect 2002; 4: 1281–90

    Article  PubMed  CAS  Google Scholar 

  89. Bozza S, Perruccio K, Montagnoli C, et al. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 2003; 102: 380714

    Article  Google Scholar 

  90. Cenci E, Mencacci A, Bacci A, et al. T cell vaccination in mice with invasive pulmonary aspergillosis. J Immunol 2000; 165: 381–8

    PubMed  CAS  Google Scholar 

  91. Cenci E, Mencacci A, Spreca A, et al. Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation. Infect Immun 2002; 70: 2375–82

    Article  PubMed  CAS  Google Scholar 

  92. Baddley JW, Stroud TP, Salzman D, et al. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001; 232: 1319–24

    Article  Google Scholar 

  93. Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34: 909–17

    Article  PubMed  Google Scholar 

  94. Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 2004; 350: 950–2

    Article  PubMed  CAS  Google Scholar 

  95. Verweij PE, Mellado E, Melchers WGJ. Multiple triazole resistant aspergillosis. N Engl J Med 2007; 356: 1481–3

    Article  PubMed  CAS  Google Scholar 

  96. Slaven JW, Anderson MJ, Sanglard D, et al. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in itraconazole resistant clinical isolate. Fungal Genet Biol 2002; 36: 199–206

    Article  PubMed  CAS  Google Scholar 

  97. Mann PA, Parmegiani RM, Wei SO, et al. Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14α-demethylase. Antimicrob Agents Chemother 2003; 47: 577–81

    Article  PubMed  CAS  Google Scholar 

  98. Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, et al. A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 2003; 47: 1120–4

    Article  PubMed  CAS  Google Scholar 

  99. Nascimento AM, Goldman GH, Park S, et al. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob Agents Chemother 2003; 47: 1719–26

    Article  PubMed  CAS  Google Scholar 

  100. Warris A, Weemaes CM, Verwaij PE. Multidrug resistance in A. fumigatus. N Engl J Med 2002; 347: 2173–4

    Article  PubMed  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. Dr Chandrasekhar has received honoraria from Pfizer, Merck & Co. and Schering-Plough, and grant support from Pfizer. Dr Krishnan has no conflicts of interest that are directly relevant to the content of this review.

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  1. Department of Internal Medicine, Division of Infectious Diseases, Wayne State University School of Medicine, Detroit, Michigan, USA

    Suganthini Krishnan-Natesan & Pranatharthi H. Chandrasekar

  2. Department of Medicine, Division of Infectious Diseases, John D. Dingell VA Medical Center, 427 Lande Building, 550 E. Canfield Ave, Detroit, Michigan, 48201, USA

    Suganthini Krishnan-Natesan

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Correspondence to Suganthini Krishnan-Natesan.

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Krishnan-Natesan, S., Chandrasekar, P.H. Current and Future Therapeutic Options in the Management of Invasive Aspergillosis. Drugs 68, 265–282 (2008). https://doi.org/10.2165/00003495-200868030-00002

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