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Aspergillosis

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Principles and Practice of Transplant Infectious Diseases

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Abstract

Aspergillus species are ubiquitous fungi that infect humans after their asexual spores are inhaled and deposited in the respiratory tract. Neutrophils and cell-mediated immunity are crucial components of host defenses that prevent invasion of Aspergillus, and these elements are often lacking or impaired in transplant recipients. Aspergillosis is the most common invasive fungal infection in hematopoietic stem cell transplant recipients and the second most common in solid organ transplant recipients. Invasive pulmonary disease is the most common site of infection, followed by sinusitis. Infection can also disseminate to the central nervous system and virtually any organ system. Use of computed tomography and biomarkers provides additional sensitivity, compared to conventional culture and microscopy-based diagnostic methods. Voriconazole and isavuconazole are treatments of choice for invasive aspergillosis, with isavuconazole having fewer adverse effects and more predictable pharmacokinetics. Adding an echinocandin to voriconazole may provide additional benefit. Prophylaxis against invasive aspergillosis with mold-active antifungal agents is indicated in certain high-risk transplant recipients.

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References

  1. Dagenais TR, Keller NP. Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev. 2009;22(3):447–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bennett JW. Aspergillus: a primer for the novice. Med Mycol. 2009;47(Suppl 1):S5–12.

    Article  PubMed  Google Scholar 

  3. Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50(8):1101–11.

    Article  PubMed  Google Scholar 

  4. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplants, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50(8):1091–100.

    Article  PubMed  Google Scholar 

  5. Perkhofer S, Lass-Florl C, Hell M, et al. The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients. Int J Antimicrob Agents. 2010;36(6):531–6.

    Article  CAS  PubMed  Google Scholar 

  6. Marr KA, Carter RA, Boeckh M, Martin P, Corey L. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100(13):4358–66.

    Article  CAS  PubMed  Google Scholar 

  7. Segal BH. Aspergillosis. N Engl J Med. 2009;360(18):1870–84.

    Article  CAS  PubMed  Google Scholar 

  8. Stergiopoulou T, Meletiadis J, Roilides E, et al. Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis. Am J Clin Pathol. 2007;127(3):349–55.

    Article  PubMed  Google Scholar 

  9. Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362(9398):1828–38.

    Article  CAS  PubMed  Google Scholar 

  10. Auletta JJ, Lazarus HM. Immune restoration following hematopoietic stem cell transplantation: an evolving target. Bone Marrow Transplant. 2005;35(9):835–57.

    Article  CAS  PubMed  Google Scholar 

  11. Wirk B, Wingard JR. Current approaches in antifungal prophylaxis in high risk hematologic malignancy and hematopoietic stem cell transplant patients. Mycopathologia. 2009;168(6):299–311.

    Article  PubMed  Google Scholar 

  12. Gil L, Styczynski J, Komarnicki M. Infectious complication in 314 patients after high-dose therapy and autologous hematopoietic stem cell transplantation: risk factors analysis and outcome. Infection. 2007;35(6):421–7.

    Article  CAS  PubMed  Google Scholar 

  13. Pagano L, Caira M, Nosari A, et al. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study—Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis. 2007;45(9):1161–70.

    Article  CAS  PubMed  Google Scholar 

  14. Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplants: biological risk factors for infection according to time after transplantation. Clin Infect Dis. 2008;47(8):1041–50.

    Article  PubMed  Google Scholar 

  15. Roilides E, Robinson T, Sein T, Pizzo PA, Walsh TJ. In vitro and ex vivo effects of cyclosporin a on phagocytic host defenses against Aspergillus fumigatus. Antimicrob Agents Chemother. 1994;38(12):2883–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Berenguer J, Allende MC, Lee JW, et al. Pathogenesis of pulmonary aspergillosis. Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression. Am J Respir Crit Care Med. 1995;152(3):1079–86.

    Article  CAS  PubMed  Google Scholar 

  17. Steinbach WJ, Reedy JL, Cramer RA Jr, Perfect JR, Heitman J. Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections. Nat Rev Microbiol. 2007;5(6):418–30.

    Article  CAS  PubMed  Google Scholar 

  18. Gavalda J, Len O, San Juan R, et al. Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clin Infect Dis. 2005;41(1):52–9.

    Article  CAS  PubMed  Google Scholar 

  19. Singh N, Arnow PM, Bonham A, et al. Invasive aspergillosis in liver transplant recipients in the 1990s. Transplantation. 1997;64(5):716–20.

    Article  CAS  PubMed  Google Scholar 

  20. Singh N, Avery RK, Munoz P, et al. Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clin Infect Dis. 2003;36(1):46–52.

    Article  PubMed  Google Scholar 

  21. Fortun J, Martin-Davila P, Moreno S, et al. Risk factors for invasive aspergillosis in liver transplant recipients. Liver Transpl. 2002;8(11):1065–70.

    Article  PubMed  Google Scholar 

  22. Singh N, Husain S. Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management. J Heart Lung Transplant. 2003;22(3):258–66.

    Article  PubMed  Google Scholar 

  23. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005;18(1):44–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Minari A, Husni R, Avery RK, et al. The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants. Transpl Infect Dis. 2002;4(4):195–200.

    Article  CAS  PubMed  Google Scholar 

  25. Singh N, Husain S. Invasive aspergillosis in solid organ transplant recipients. Am J Transplant. 2009;9(Suppl 4):S180–91.

    Article  PubMed  Google Scholar 

  26. Husni RN, Gordon SM, Longworth DL, et al. Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients. Clin Infect Dis. 1998;26(3):753–5.

    Article  CAS  PubMed  Google Scholar 

  27. Paradowski LJ. Saprophytic fungal infections and lung transplantation – revisited. J Heart Lung Transplant. 1997;16(5):524–31.

    CAS  PubMed  Google Scholar 

  28. Fernandez-Ruiz M, Silva JT, San-Juan R, et al. Aspergillus tracheobronchitis: report of 8 cases and review of the literature. Medicine (Baltimore). 2012;91(5):261–73.

    Article  Google Scholar 

  29. Drakos PE, Nagler A, Or R, et al. Invasive fungal sinusitis in patients undergoing bone marrow transplantation. Bone Marrow Transplant. 1993;12(3):203–8.

    CAS  PubMed  Google Scholar 

  30. Savage DG, Taylor P, Blackwell J, et al. Paranasal sinusitis following allogeneic bone marrow transplant. Bone Marrow Transplant. 1997;19(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  31. DelGaudio JM, Clemson LA. An early detection protocol for invasive fungal sinusitis in neutropenic patients successfully reduces extent of disease at presentation and long term morbidity. Laryngoscope. 2009;119(1):180–3.

    Article  PubMed  Google Scholar 

  32. Walsh TJ, Hier DB, Caplan LR. Aspergillosis of the central nervous system: clinicopathological analysis of 17 patients. Ann Neurol. 1985;18(5):574–82.

    Article  CAS  PubMed  Google Scholar 

  33. Pagano L, Ricci P, Montillo M, et al. Localization of aspergillosis to the central nervous system among patients with acute leukemia: report of 14 cases. Gruppo Italiano Ematologiche dell’Adulto Infection Program. Clin Infect Dis. 1996;23(3):628–30.

    Article  CAS  PubMed  Google Scholar 

  34. Hunt KE, Glasgow BJ. Aspergillus endophthalmitis. An unrecognized endemic disease in orthotopic liver transplantation. Ophthalmology. 1996;103(5):757–67.

    Article  CAS  PubMed  Google Scholar 

  35. Walsh TJ. Primary cutaneous aspergillosis – an emerging infection among immunocompromised patients. Clin Infect Dis. 1998;27(3):453–7.

    Article  CAS  PubMed  Google Scholar 

  36. van Burik JA, Colven R, Spach DH. Cutaneous aspergillosis. J Clin Microbiol. 1998;36(11):3115–21.

    PubMed  PubMed Central  Google Scholar 

  37. De Pauw B, Walsh TJ, Donnelly JP, et al. 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(12):1813–21.

    Article  PubMed  Google Scholar 

  38. Gray LD, Roberts GD. Laboratory diagnosis of systemic fungal diseases. Infect Dis Clin N Am. 1988;2(4):779–803.

    CAS  Google Scholar 

  39. Larone D. Medically important fungi: a guide to identification. 5th ed. Washington (D.C.): ASM Press; 2011.

    Google Scholar 

  40. Paterson DL, Singh N. Invasive aspergillosis in transplant recipients. Medicine (Baltimore). 1999;78(2):123–38.

    Article  CAS  Google Scholar 

  41. Horvath JA, Dummer S. The use of respiratory-tract cultures in the diagnosis of invasive pulmonary aspergillosis. Am J Med. 1996;100(2):171–8.

    Article  CAS  PubMed  Google Scholar 

  42. Wald A, Leisenring W, van Burik JA, Bowden RA. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J Infect Dis. 1997;175(6):1459–66.

    Article  CAS  PubMed  Google Scholar 

  43. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006;42(10):1417–27.

    Article  CAS  PubMed  Google Scholar 

  44. Husain S, Kwak EJ, Obman A, et al. Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant. 2004;4(5):796–802.

    Article  PubMed  Google Scholar 

  45. Singh N, Winston DJ, Limaye AP, et al. Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients. Transplantation. 2015;99(12):2543–50.

    Article  CAS  PubMed  Google Scholar 

  46. Marr KA, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis. 2005;40(12):1762–9.

    Article  CAS  PubMed  Google Scholar 

  47. Walsh TJ, Shoham S, Petraitiene R, et al. Detection of galactomannan antigenemia in patients receiving piperacillin-tazobactam and correlations between in vitro, in vivo, and clinical properties of the drug-antigen interaction. J Clin Microbiol. 2004;42(10):4744–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mikulska M, Furfaro E, Del Bono V, et al. Piperacillin/tazobactam (Tazocin) seems to be no longer responsible for false-positive results of the galactomannan assay. J Antimicrob Chemother. 2012;67(7):1746–8.

    Article  CAS  PubMed  Google Scholar 

  49. Asano-Mori Y, Kanda Y, Oshima K, et al. False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem transplantation. J Antimicrob Chemother. 2008;61(2):411–6.

    Article  CAS  PubMed  Google Scholar 

  50. Mennink-Kersten MA, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis. 2004;4(6):349–57.

    Article  CAS  PubMed  Google Scholar 

  51. Swanink CM, Meis JF, Rijs AJ, Donnelly JP, Verweij PE. Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan. J Clin Microbiol. 1997;35(1):257–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Tortorano AM, Esposto MC, Prigitano A, et al. Cross-reactivity of Fusarium spp. in the Aspergillus galactomannan enzyme-linked immunosorbent assay. J Clin Microbiol. 2012;50(3):1051–3.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Maertens J, Maertens V, Theunissen K, et al. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis. 2009;49(11):1688–93.

    Article  PubMed  Google Scholar 

  54. D’Haese J, Theunissen K, Vermeulen E, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol. 2012;50(4):1258–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Husain S, Clancy CJ, Nguyen MH, et al. Performance characteristics of the platelia Aspergillus enzyme immunoassay for detection of Aspergillus galactomannan antigen in bronchoalveolar lavage fluid. Clin Vaccine Immunol. 2008;15(12):1760–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Husain S, Paterson DL, Studer SM, et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation. 2007;83(10):1330–6.

    Article  CAS  PubMed  Google Scholar 

  57. Pickering JW, Sant HW, Bowles CA, Roberts WL, Woods GL. Evaluation of a (1->3)-beta-D-glucan assay for diagnosis of invasive fungal infections. J Clin Microbiol. 2005;43(12):5957–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. Beta-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70.

    Article  CAS  PubMed  Google Scholar 

  59. Lamoth F, Cruciani M, Mengoli C, et al. Beta-glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematologic malignancies: a systematic review and meta-analysis of cohort studies from the Thrid European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis. 2012;54(5):633–43.

    Article  PubMed  Google Scholar 

  60. Kato A, Takita T, Furuhashi M, Takahashi T, Maruyama Y, Hishida A. Elevation of blood (1-->3)-beta-D-glucan concentrations in hemodialysis patients. Nephron. 2001;89(1):15–9.

    Article  CAS  PubMed  Google Scholar 

  61. Ogawa M, Hori H, Niiguchi S, Azuma E, Komada Y. False-positive plasma (1-->3)-beta-D-glucan test following immunoglobulin product replacement in an adult bone marrow recipient. Int J Hematol. 2004;80(1):97–8.

    Article  PubMed  Google Scholar 

  62. Usami M, Ohata A, Horiuchi T, Nagasawa K, Wakabayashi T, Tanaka S. Positive (1-->3)-beta-D-glucan in blood components and release of (1-->3)-beta-D-glucan from depth-type membrane filters for blood processing. Transfusion. 2002;42(9):1189–95.

    Article  CAS  PubMed  Google Scholar 

  63. Mennink-Kersten MA, Warris A, Verweij PE. 1,3-beta-D-glucan in patients receiving intravenous amoxicillin-clavulanic acid. N Engl J Med. 2006;354(26):2834–5.

    Article  CAS  PubMed  Google Scholar 

  64. Nakao A, Yasui M, Kawagoe T, Tamura H, Tanaka S, Takagi H. False-positive endotoxemia derives from gauze glucan after hepatectomy for hepatocellular carcinoma with cirrhosis. Hepato-Gastroenterology. 1997;44(17):1413–8.

    CAS  PubMed  Google Scholar 

  65. Mennink-Kersten MA, Ruegebrink D, Verweij PE. Pseudomonas aeruginosa as a cause of 1,3-beta-D-glucan assay reactivity. Clin Infect Dis. 2008;46(12):1930–1.

    Article  PubMed  Google Scholar 

  66. Springer J, Lackner M, Nachbaur D, et al. Prospective multicentre PCR-based aspergillus DNA screening in high-risk patients with and without primary antifungal prophylaxis. Clin Microbiol Infect. 2016;22(1):80–6.

    Article  CAS  PubMed  Google Scholar 

  67. 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(3):373–9.

    Article  PubMed  Google Scholar 

  68. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology. 1985;157(3):611–4.

    Article  CAS  PubMed  Google Scholar 

  69. Kami M, Kishi Y, Hamaki T, et al. The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients. Mycoses. 2002;45(8):287–94.

    Article  CAS  PubMed  Google Scholar 

  70. Bruno C, Minniti S, Vassanelli A, Pozzi-Mucelli R. Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. J Thorac Imaging. 2007;22(2):160–5.

    Article  PubMed  Google Scholar 

  71. Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis. 2011;52(9):1144–55.

    Article  PubMed  PubMed Central  Google Scholar 

  72. 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(1):253–9.

    Article  CAS  PubMed  Google Scholar 

  73. Stanzani M, Battista G, Sassi C, et al. Computed tomographic pulmonary angiography for diagnosis of invasive mold diseases in patients with hematological malignancies. Clin Infect Dis. 2012;54(5):610–6.

    Article  PubMed  Google Scholar 

  74. Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):e1–e60.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15.

    Article  CAS  PubMed  Google Scholar 

  76. 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(2):201–11.

    Article  CAS  PubMed  Google Scholar 

  77. Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis. 2003;36(5):630–7.

    Article  CAS  PubMed  Google Scholar 

  78. Park WB, Kim NH, Kim KH, et al. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis. 2012;55(8):1080–7.

    Article  CAS  PubMed  Google Scholar 

  79. Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760–9.

    Article  CAS  PubMed  Google Scholar 

  80. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–37.

    Article  CAS  PubMed  Google Scholar 

  81. Cornely OA, Maertens J, Bresnik M, et al. 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(10):1289–97.

    Article  CAS  PubMed  Google Scholar 

  82. Leenders AC, Daenen S, Jansen RL, et al. Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections. Br J Haematol. 1998;103(1):205–12.

    Article  CAS  PubMed  Google Scholar 

  83. Bowden R, Chandrasekar 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;35(4):359–66.

    Article  CAS  PubMed  Google Scholar 

  84. Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999;340(10):764–71.

    Article  CAS  PubMed  Google Scholar 

  85. Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment ofrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis. 2000;31(5):1155–63.

    Article  CAS  PubMed  Google Scholar 

  86. Hachem RY, Boktour MR, Hanna HA, et al. Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy. Cancer. 2008;112(6):1282–7.

    Article  CAS  PubMed  Google Scholar 

  87. Kirkpatrick WR, McAtee RK, Fothergill AW, Loebenberg D, Rinaldi MG, Patterson TF. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis. Antimicrob Agents Chemother. 2000;44(3):780–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. Antimicrob Agents Chemother. 2001;45(3):857–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 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;44(1):2–12.

    Article  CAS  PubMed  Google Scholar 

  90. Pfaller MA, Messer SA, Hollis RJ, Jones RN. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob Agents Chemother. 2002;46(4):1032–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cappelletty D, Eiselstein-McKitrick K. The echinocandins. Pharmacotherapy. 2007;27(3):369–88.

    Article  CAS  PubMed  Google Scholar 

  92. Maertens J, Raad I, Petrikkos G, 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(11):1563–71.

    Article  CAS  PubMed  Google Scholar 

  93. Wiederhold NP, Cota JM, Frei CR. Micafungin in the treatment of invasive candidiasis and invasive aspergillosis. Infect Drug Resist. 2008;1:63–77.

    CAS  PubMed  Google Scholar 

  94. 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(5):337–49.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Kontoyiannis DP, Ratanatharathorn V, Young JA, et al. Micafungin alone or in combination with other systemic antifungal therapies in hematopoietic stem cell transplant recipients with invasive aspergillosis. Transpl Infect Dis. 2009;11(1):89–93.

    Article  CAS  PubMed  Google Scholar 

  96. Petraitis V, Petraitiene R, Sarafandi AA, et al. Combination therapy in treatment of experimental pulmonary aspergillosis. J Infect Dis. 2003;187(12):1834–43.

    Article  CAS  PubMed  Google Scholar 

  97. 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(8):2564–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39(6):797–802.

    Article  CAS  PubMed  Google Scholar 

  99. Meletiadis J, Petraitis V, Petraitiene R, et al. Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation. J Infect Dis. 2006;194(7):1008–18.

    Article  CAS  PubMed  Google Scholar 

  100. Kontoyiannis DP, Boktour M, Hanna H, Torres HA, 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(11):2334–7.

    Article  CAS  PubMed  Google Scholar 

  101. Marr KA, Sclamm HT, Hebrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2):81–9.

    Article  PubMed  Google Scholar 

  102. Collette N, Van der Auwera P, Meunier F, Lambert C, Sculier JP, Coune A. Tissue distribution and bioactivity of amphotericin B administered in liposomes to cancer patients. J Antimicrob Chemother. 1991;27(4):535–48.

    Article  CAS  PubMed  Google Scholar 

  103. Hajdu R, Thompson R, Sundelof JG, et al. Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872). Antimicrob Agents Chemother. 1997;41(11):2339–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lutsar I, Roffey S, Troke P. Voriconazole concentrations in the cerebrospinal fluid and brain tissue of Guinea pigs and immunocompromised patients. Clin Infect Dis. 2003;37(5):728–32.

    Article  PubMed  Google Scholar 

  105. Denning DW. Therapeutic outcome in invasive aspergillosis. Clin Infect Dis. 1996;23(3):608–15.

    Article  CAS  PubMed  Google Scholar 

  106. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32(3):358–66.

    Article  CAS  PubMed  Google Scholar 

  107. Schwartz S, Ruhnke M, Ribaud P, et al. Improved outcome in central nervous system aspergillosis, using voriconazole treatment. Blood. 2005;106(8):2641–5.

    Article  CAS  PubMed  Google Scholar 

  108. 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(7):2343–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Walsh TJ, Petraitis V, Petraitiene R, et al. Experimental pulmonary aspergillosis due to Aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J Infect Dis. 2003;188(2):305–19.

    Article  CAS  PubMed  Google Scholar 

  110. Steinbach WJ, Benjamin DK Jr, Kontoyiannis DP, et al. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin Infect Dis. 2004;39(2):192–8.

    Article  PubMed  Google Scholar 

  111. Balajee SA, Nickle D, Varga J, Marr KA. Molecular studies reveal frequent misidentification of Aspergillus fumigatus by morphotyping. Eukaryot Cell. 2006;5(10):1705–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Vinh DC, Shea YR, Sugui JA, et al. Invasive aspergillosis due to Neosartorya udagawae. Clin Infect Dis. 2009;49(1):102–11.

    Article  PubMed  Google Scholar 

  113. Verweij PE, Mellado E, Melchers WJ. Multiple-triazole-resistant aspergillosis. N Engl J Med. 2007;356(14):1481–3.

    Article  CAS  PubMed  Google Scholar 

  114. Alanio A, Sitterle E, Liance M, et al. Low prevalence of resistance to azoles in Aspergillus fumigatus in a French cohort of patients treated for hematological malignancies. J Antimicrob Chemother. 2011;66(2):371–4.

    Article  CAS  PubMed  Google Scholar 

  115. 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(4):531–40.

    Article  PubMed  Google Scholar 

  116. 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(11):1584–91.

    Article  PubMed  Google Scholar 

  117. Lowenberg B, Suciu S, Archimbaud E, et al. Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years or older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer in Dutch Belgian Hemato-Oncology Cooperative Group. Blood. 1997;90(8):2952–61.

    CAS  PubMed  Google Scholar 

  118. Sung L, Nathan PC, Alibhai SM, Tomlinson GA, Beyene J. Meta-analysis: effect of prophylactic hematopoietic colony-stimulating factors on mortality and outcomes of infection. Ann Intern Med. 2007;147(6):400–11.

    Article  PubMed  Google Scholar 

  119. Dignani MC, Anaissie EJ, Hester JP, et al. Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions: a pilot study. Leukemia. 1997;11(10):1621–30.

    Article  CAS  PubMed  Google Scholar 

  120. Price TH, Boeckh M, Harrison RW, et al. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood. 2015;126(18):2153–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Caillot D, Mannone L, Cuisenier B, Couaillier JF. Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients. Clin Microbiol Infect. 2001;7(Suppl 2):54–61.

    Article  PubMed  Google Scholar 

  122. Matt P, Bernet F, Habicht J, et al. Predicting outcome after lung resection for invasive pulmonary aspergillosis in patients with neutropenia. Chest. 2004;126(6):1783–8.

    Article  PubMed  Google Scholar 

  123. Suslu AE, Ogretmenoglu O, Suslu N, Yucel OT, Onerci TM. Acute invasive fungal rhinosinusitis: our experience with 19 patients. Eur Arch Otorhinolaryngol. 2009;266(1):77–82.

    Article  PubMed  Google Scholar 

  124. Wingard JR, Carter SL, Walsh TJ, et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116(24):5111–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. van Burik JA, 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(10):1407–16.

    Article  PubMed  Google Scholar 

  126. 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(4):335–47.

    Article  CAS  PubMed  Google Scholar 

  127. Gergis U, Markey K, Greene J, et al. Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD. Bone Marrow Transplant. 2010;45(4):662–7.

    Article  CAS  PubMed  Google Scholar 

  128. Offner F, Cordonnier C, Ljungman P, et al. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis. 1998;5:1098–103.

    Article  Google Scholar 

  129. Cordonnier C, Rovira M, Maertens J, et al. Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study. Haematologica. 2010;95(10):1762–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Reichenspurner H, Gamberg P, Nitschke M, et al. Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis. Transplant Proc. 1997;29(1–2):627–8.

    Article  CAS  PubMed  Google Scholar 

  132. Drew RH, Dodds Ashley E, Benjamin DK Jr, Duane Davis R, 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(2):232–7.

    Article  CAS  PubMed  Google Scholar 

  133. Sole A. Invasive fungal infections in lung transplantation: role of aerosolised amphotericin B. Int J Antimicrob Agents. 2008;32(Suppl 2):S161–5.

    Article  CAS  PubMed  Google Scholar 

  134. Wahidi MM, Willner DA, Snyder LD, Hardison JL, Chia JY, Palmer SM. Diagnosis and outcome of early pleural space infection following lung transplantation. Chest. 2009;135(2):484–91.

    Article  PubMed  Google Scholar 

  135. Husain S, Paterson DL, Studer S, et al. Voriconazole prophylaxis in lung transplant recipients. Am J Transplant. 2006;6(12):3008–16.

    Article  CAS  PubMed  Google Scholar 

  136. Fortun J, Martin-Davila P, Moreno S, et al. Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients. J Antimicrob Chemother. 2003;52(5):813–9.

    Article  CAS  PubMed  Google Scholar 

  137. Fortun J, Martin-Davila P, Montejo M, et al. Prophylaxis with caspofungin for invasive fungal infections in high-risk liver transplant recipients. Transplantation. 2009;87(3):424–35.

    Article  CAS  PubMed  Google Scholar 

  138. Praz-Christinaz SM, Lazor-Blanchet C, Binet I, Boillat MA, Danuser B. Occupational risk assessment of aspergillosis after renal transplantation. Transpl Infect Dis. 2007;9(3):175–81.

    Article  CAS  PubMed  Google Scholar 

  139. Oren I, Haddad N, Finkelstein R, Rowe JM. Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: before and after chemoprophylaxis and institution of HEPA filters. Am J Hematol. 2001;66(4):257–62.

    Article  CAS  PubMed  Google Scholar 

  140. Baddley JW, Andes DR, Marr KA, et al. Factors associated with mortality in transplant patients with invasive aspergillosis. Clin Infect Dis. 2010;50(12):1559–67.

    Article  PubMed  Google Scholar 

  141. Nivoix Y, Velten M, Letscher-Bru V, et al. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin Infect Dis. 2008;47(9):1176–84.

    Article  PubMed  Google Scholar 

  142. Parody R, Martino R, Sanchez F, Subira M, Hidalgo A, Sierra J. Predicting survival in adults with invasive aspergillosis during therapy for hematological malignancies or after hematopoietic stem cell transplantation: single-center analysis and validation of the Seattle, French, and Strasbourg prognostic indexes. Am J Hematol. 2009;84(9):571–8.

    Article  PubMed  Google Scholar 

  143. Miceli MH, Grazziutti ML, Woods G, et al. Strong correlation between serum Aspergillus galactomannan index and outcome of aspergillosis in patients with hematological cancer: clinical and research implications. Clin Infect Dis. 2008;46(9):1412–22.

    Article  PubMed  Google Scholar 

  144. Woods G, Miceli MH, Grazziutti ML, Zhao W, Barlogie B, Anaissie E. Serum Aspergillus galactomannan antigen values strongly correlate with outcome of invasive aspergillosis: a study of 56 patients with hematologic cancer. Cancer. 2007;110(4):830–4.

    Article  PubMed  Google Scholar 

  145. Koo S, Bryar JM, Baden LR, Marty FM. Prognostic features of galactomannan antigenemia in galactomannan-positive invasive aspergillosis. J Clin Microbiol. 2010;48(4):1255–60.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Weill Cornell Medicine, New York, NY, USA

    Michael J. Satlin & Samantha E. Jacobs

  2. Transplant Infectious Diseases Program, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, Department of Medicine, New York, NY, USA

    Samantha E. Jacobs

  3. Transplantation-Oncology Infectious Diseases Program, New York-Presbyterian/Weill Cornell Medical Center, New York, NY, USA

    Thomas J. Walsh

  4. Department of Pediatrics, New York-Presbyterian/Weill Cornell Medical Center, New York, NY, USA

    Thomas J. Walsh

  5. Department of Microbiology and Immunology, New York-Presbyterian/Weill Cornell Medical Center, New York, NY, USA

    Thomas J. Walsh

  6. Transplant Infectious Diseases Program, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Thomas J. Walsh

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  1. Michael J. Satlin
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  3. Thomas J. Walsh
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Correspondence to Michael J. Satlin .

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  1. Clinical Associate Professor of Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX, USA

    Amar Safdar

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Satlin, M.J., Jacobs, S.E., Walsh, T.J. (2019). Aspergillosis. In: Safdar, A. (eds) Principles and Practice of Transplant Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9034-4_33

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