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Aspergillosis

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Abstract

The opportunistic mold Aspergillus is the etiologic agent responsible for a variety of infections and conditions referred to as aspergillosis. These manifestations include a spectrum of diseases from allergic responses to the organism (allergic bronchopulmonary aspergillosis), to colonization with Aspergillus spp. (aspergilloma or fungus ball and other superficial conditions, such as external ear colonization) and invasive infection (invasive pulmonary aspergillosis and other clinical syndromes of tissue invasion).

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References

  1. Patterson TF, Kirkpatrick WR, White M, I3 Aspergillus Study Group, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. Medicine (Baltimore). 2000;79:250–60.

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.

    CAS  PubMed  Google Scholar 

  4. 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.

    CAS  PubMed  Google Scholar 

  5. Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998;26:781–803.

    CAS  PubMed  Google Scholar 

  6. Micheli P. Nova plantarum genra juxta Tournefortii methodum disposita. Florence: Bernardo Paperini; 1729.

    Google Scholar 

  7. Mackenzie DW. Aspergillus in man. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G, editors. Proceedings of the Second International Symposium on Topics in Mycology; 1987. Antwerp, Belgium: University of Antwerp; 1987. p. 1–8.

    Google Scholar 

  8. Kwon-Chung KJ. Aspergillus: Diagnosis and description of the genus. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G, editors. Proceedings of the Second International Symposium on Topics in Mycology; 1987. Antwerp: University of Antwerp; 1987. p. 11–21.

    Google Scholar 

  9. Virchow V. Breitage zur lehre von den beim menschen vorkommenden pfanzlichen parasiten. Virchows Archiv 1856:557.

    Google Scholar 

  10. Kwon-Chung KJ, Bennett JE. Medical Mycology. Philadelphia: Lea & Febiger; 1992.

    Google Scholar 

  11. Fresenius G. Beitrage zur Mykologie. Frankfurt: HL Bronner; 1863.

    Google Scholar 

  12. Deve F. Une nouvelle forme anatomoradiologique de mycose pulmonaire primitive: le megamycetome intrabronchetasique. Arch Med Chir Appl Respir. 1938;13:337–61.

    Google Scholar 

  13. Hinson K, Moon A, Plummer N. Broncho-pulmonary aspergillosis. A review and a report of eight new cases. Thorax. 1952;7:317–33.

    CAS  PubMed  Google Scholar 

  14. Rankin N. Disseminated aspergillosis and moniliasis associated with agranulocytosis and antibiotic therapy. Br Med J. 1953;183:918–9.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  16. Link H. Observations in ordines plantarum naturales. Gesellschaft Naturforschender Freunde zu Berlin, Magazin. 1809;3:1.

    Google Scholar 

  17. Thom C, Church M. The Aspergilli. Baltimore: Williams & Wilkins; 1926.

    Google Scholar 

  18. Raper B, Fennel J. The Genus Aspergillus. Baltimore: Williams & Wilkins; 1965.

    Google Scholar 

  19. Patterson TF. Chapter 258. Aspergillus species. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2009. p. 3241–55.

    Google Scholar 

  20. Sutton DA. Rare and emerging agents of hyalohyphomycosis. Curr Fungal Infect Reports. 2008;2:134–42.

    Google Scholar 

  21. Summerbell R. Ascomycetes. Aspergillus, Fusarium, Sporothrix, Piedraia, and Their Relatives. In: Howard DH, editor. Pathogenic Fungi in Humans and Animals. 2nd ed. New York: Marcel Dekker; 2003. p. 237–498.

    Google Scholar 

  22. Balajee SA, Houbraken J, Verweij PE, et al. Aspergillus species identification in the clinical setting. Stud Mycol. 2007;59:39–46.

    CAS  PubMed  Google Scholar 

  23. Klich M, Pitt J. A laboratory guide to common Aspergillus species and their teleomorphs. North Ryde, New South Wales, Australia: Commonwealth Scientific and Industrial Research Organization; 1988.

    Google Scholar 

  24. O’Gorman CM, Fuller HT, Dyer PS. Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus. Nature. 2009;457:471–4.

    PubMed  Google Scholar 

  25. Pitt JI, Samson RA. Nomenclatural considerations in naming species of Aspergillus and its teleomorphs. Stud Mycol. 2007;59:67–70.

    CAS  PubMed  Google Scholar 

  26. Geiser DM, Klich MA, Frisvad JC, Peterson SW, Varga J, Samson RA. The current status of species recognition and identification in Aspergillus. Stud Mycol. 2007;59:1–10.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  28. Pitt J. The current role of Aspergillus and Penicillium in human and animal health. J Med Vet Mycol. 1994;1:17–21.

    Google Scholar 

  29. Sutton DA, Fothergill AW, Rinaldi MG, editors. Guide to Clinically Significant Fungi. 1st ed. Baltimore: Williams & Wilkins; 1998.

    Google Scholar 

  30. Balajee SA, Gribskov JL, Hanley E, Nickle D, Marr KA. Aspergillus lentulus sp. nov., a New Sibling Species of A. fumigatus. Eukaryot Cell. 2005;4:625–32.

    CAS  PubMed  Google Scholar 

  31. Balajee SA, Baddley JW, Peterson SW, et al. Aspergillus alabamensis, a new clinically relevant species in the section Terrei. Eukaryot Cell. 2009;8:713–22.

    CAS  PubMed  Google Scholar 

  32. Sutton DA, Fothergill AW, Rinaldi MG. Aspergillus in vitro antifungal susceptibility data: New millennium trends (abstract 16). In: Abstracts of Advances Against Aspergillosis, September 9–11, 2004, San Francisco, CA; 2004.

    Google Scholar 

  33. Perfect JR, Cox GM, Lee JY, et al. The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin Infect Dis. 2001;33:1824–33.

    CAS  PubMed  Google Scholar 

  34. Anaissie EJ, Stratton SL, Dignani MC, et al. Pathogenic Aspergillus species recovered from a hospital water system: A 3-year prospective study. Clin Infect Dis. 2002;34:780–9.

    PubMed  Google Scholar 

  35. Balajee SA, Imhof A, Gribskov JL, Marr KA. Determination of antifungal drug susceptibilities of Aspergillus species by a fluorescence-based microplate assay. J Antimicrob Chemother. 2005;55:102–5.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  37. Steinbach WJ, Perfect JR, Schell WA, Walsh TJ, Benjamin Jr DK. In vitro analyses, animal models, and 60 clinical cases of invasive Aspergillus terreus infection. Antimicrob Agents Chemother. 2004;48:3217–25.

    CAS  PubMed  Google Scholar 

  38. Geyer SJ, Surampudi RK. Photo quiz - Birefringent crystals in a pulmonary specimen. Clin Infect Dis. 2002;34(481):551–2.

    Google Scholar 

  39. Kontoyiannis DP, Lewis RE, May GS, Osherov N, Rinaldi MG. Aspergillus nidulans is frequently resistant to amphotericin B. Mycoses. 2002;45:406–7.

    CAS  PubMed  Google Scholar 

  40. Anaissie EJ, Costa SF. Nosocomial aspergillosis is waterborne. Clin Infect Dis. 2001;33:1546–8.

    CAS  PubMed  Google Scholar 

  41. Walsh TJ. Primary cutaneous aspergillosis – An emerging ­infection among immunocompromised patients. Clin Infect Dis. 1998;27:453–7.

    CAS  PubMed  Google Scholar 

  42. Cramer Jr RA, Gamcsik MP, Brooking RM, et al. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell. 2006;5:972–80.

    CAS  PubMed  Google Scholar 

  43. Spikes S, Xu R, Nguyen CK, et al. Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence. J Infect Dis. 2008;197:479–86.

    CAS  PubMed  Google Scholar 

  44. Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 1999;12:310–50.

    CAS  PubMed  Google Scholar 

  45. Alp S, Arikan S. Investigation of extracellular elastase, acid proteinase and phospholipase activities as putative virulence factors in clinical isolates of Aspergillus species. J Basic Microbiol. 2008;48:331–7.

    PubMed  Google Scholar 

  46. Schaffner A, Douglas H, Braude A. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J Clin Invest. 1982;69:617–31.

    CAS  PubMed  Google Scholar 

  47. Aimanianda V, Bayry J, Bozza S, et al. Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature. 2009;460:1117–21.

    CAS  PubMed  Google Scholar 

  48. Mircescu MM, Lipuma L, van Rooijen N, Pamer EG, Hohl TM. Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection. J Infect Dis. 2009;200:647–56.

    CAS  PubMed  Google Scholar 

  49. Levitz SM, Selsted ME, Ganz T, Lehrer RI, Diamond RD. In vitro killing of spores and hyphae of Aspergillus fumigatus and Rhizopus oryzae by rabbit neutrophil cationic peptides and bronchoalveolar macrophages. J Infect Dis. 1986;154:483–9.

    CAS  PubMed  Google Scholar 

  50. Washburn RG, Gallin JI, Bennett JE. Oxidative killing of Aspergillus fumigatus proceeds by parallel myeloperoxidase-dependent and -independent pathways. Infect Immun. 1987;55:2088–92.

    CAS  PubMed  Google Scholar 

  51. Crosdale DJ, Poulton KV, Ollier WE, Thomson W, Denning DW. Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis. J Infect Dis. 2001;184:653–6.

    CAS  PubMed  Google Scholar 

  52. Lambourne J, Agranoff D, Herbrecht R, et al. Association of mannose-binding lectin deficiency with acute invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2009;49:1486–91.

    CAS  PubMed  Google Scholar 

  53. Young RC, Bennett JE. Invasive aspergillosis. Absence of detectable antibody response. Am Rev Resp Dis 1971;104:710–6.

    Google Scholar 

  54. Segal BH, Romani LR. Invasive aspergillosis in chronic granulomatous disease. Med Mycol. 2009;47 Suppl 1:S282–90.

    CAS  PubMed  Google Scholar 

  55. Ng T, Robson G, Denning DW. Hydrocortisone-enchanced growth of Aspergillus spp implications for pathogenesis. Microbiology. 1994;140:2475–80.

    CAS  PubMed  Google Scholar 

  56. Roilides E, Uhlig K, Venzon D, Pizzo PA, Walsh TJ. Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infect Immun. 1993;61:4870–7.

    CAS  PubMed  Google Scholar 

  57. Cenci E, Perito S, Enssle KH, et al. Th1 and Th2 cytokines in mice with invasive aspergillosis. Infect Immun. 1997;65:564–70.

    CAS  PubMed  Google Scholar 

  58. Segal BH. Aspergillosis. N Engl J Med. 2009;360:1870–84.

    CAS  PubMed  Google Scholar 

  59. Meier A, Kirschning CJ, Nikolaus T, Wagner H, Heesemann J, Ebel F. Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages. Cell Microbiol. 2003;5:561–70.

    CAS  PubMed  Google Scholar 

  60. Marr KA, Balajee SA, Hawn TR, et al. Differential role of MyD88 in macrophage-mediated responses to opportunistic fungal pathogens. Infect Immun. 2003;71:5280–6.

    CAS  PubMed  Google Scholar 

  61. Mambula SS, Sau K, Henneke P, Golenbock DT, Levitz SM. Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus. J Biol Chem. 2002;277:39320–6.

    CAS  PubMed  Google Scholar 

  62. Bochud PY, Chien JW, Marr KA, et al. Toll-like receptor 4 ­polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med. 2008;359:1766–77.

    CAS  PubMed  Google Scholar 

  63. Zaas AK, Liao G, Chien JW, et al. Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet. 2008;4:e1000101.

    PubMed  Google Scholar 

  64. Agarwal R. Allergic bronchopulmonary aspergillosis. Chest. 2009;135:805–26.

    PubMed  Google Scholar 

  65. Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis–state of the art: cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003;37 Suppl 3:S225–64.

    PubMed  Google Scholar 

  66. Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol. 2002;110:685–92.

    PubMed  Google Scholar 

  67. Hope WW, Walsh TJ, Denning DW. The invasive and saprophytic syndromes due to Aspergillus spp. Med Mycol. 2005;43 Suppl 1:S207–38.

    PubMed  Google Scholar 

  68. Vaid M, Kaur S, Sambatakou H, Madan T, Denning DW, Sarma PU. Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med. 2007;45:183–6.

    CAS  PubMed  Google Scholar 

  69. Partridge-Hinckley K, Liddell GM, Almyroudis NG, Segal BH. Infection control measures to prevent invasive mould diseases in hematopoietic stem cell transplant recipients. Mycopathologia. 2009;168(6):329–37.

    PubMed  Google Scholar 

  70. Warris A, Bjorneklett A, Gaustad P. Invasive pulmonary aspergillosis associated with infliximab therapy. N Engl J Med. 2001;344:1099–100.

    CAS  PubMed  Google Scholar 

  71. Meersseman W, Van Wijngaerden E. Invasive aspergillosis in the ICU: an emerging disease. Intensive Care Med. 2007;33:1679–81.

    PubMed  Google Scholar 

  72. Gerson SL, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassileth PA. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med. 1984;100:345–51.

    CAS  PubMed  Google Scholar 

  73. Portugal RD, Garnica M, Nucci M. Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve. J Clin Oncol. 2009;27:3849–54.

    PubMed  Google Scholar 

  74. Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis. 2001;32:1319–24.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  76. Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909–17.

    PubMed  Google Scholar 

  77. 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.

    CAS  PubMed  Google Scholar 

  78. De Pauw BE, Donnelly JP. Prophylaxis and aspergillosis – has the principle been proven? N Engl J Med. 2007;356:409–11.

    PubMed  Google Scholar 

  79. Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.

    PubMed  Google Scholar 

  80. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  82. 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;41:52–9.

    CAS  PubMed  Google Scholar 

  83. Haiduven D. Nosocomial aspergillosis and building construction. Med Mycol 2009;47:S210–6.

    Google Scholar 

  84. Patterson JE, Peters J, Calhoon JH, et al. Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients. Transpl Infect Dis. 2000;2:22–8.

    CAS  PubMed  Google Scholar 

  85. Patterson JE, Zidouh A, Miniter P, Andriole VT, Patterson TF. Hospital epidemiologic surveillance for invasive aspergillosis: patient demographics and the utility of antigen detection. Infect Control Hosp Epidemiol. 1997;18:104–8.

    CAS  PubMed  Google Scholar 

  86. Thompson GR 3rd, Patterson TF. Pulmonary aspergillosis. Semin Respir Crit Care Med. 2008;29:103–10.

    PubMed  Google Scholar 

  87. Ferguson BJ. Fungus balls of the paranasal sinuses. Otolaryngol Clin North Am. 2000;33:389–98.

    CAS  PubMed  Google Scholar 

  88. Kauffman CA. Quandary about treatment of aspergillomas persists. Lancet. 1996;347:1640.

    CAS  PubMed  Google Scholar 

  89. Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis. 2003;37 Suppl 3:S265–80.

    PubMed  Google Scholar 

  90. Kaur R, Mittal N, Kakkar M, Aggarwal AK, Mathur MD. Otomycosis: a clinicomycologic study. Ear Nose Throat J. 2000;79:606–9.

    CAS  PubMed  Google Scholar 

  91. Parize P, Chandesris MO, Lanternier F, et al. Antifungal therapy of Aspergillus invasive otitis externa: efficacy of voriconazole and review. Antimicrob Agents Chemother. 2009;53:1048–53.

    CAS  PubMed  Google Scholar 

  92. Rosenberg M, Patterson R, Mintzer R, Cooper B, Roberts MC, Harris K. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med. 1977;86:405–14.

    CAS  PubMed  Google Scholar 

  93. Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med. 1982;96:286–91.

    CAS  PubMed  Google Scholar 

  94. Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000;342:756–62.

    CAS  PubMed  Google Scholar 

  95. DeShazo RD, Chapin K, Swain RE. Fungal sinusitis. N Engl J Med. 1997;337:254–9.

    CAS  PubMed  Google Scholar 

  96. Latge JP. The pathobiology of Aspergillus fumigatus. Trends Microbiol. 2001;9:382–9.

    CAS  PubMed  Google Scholar 

  97. 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;39:1563–71.

    CAS  PubMed  Google Scholar 

  98. 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;35:359–66.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  100. 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;11:89–93.

    CAS  PubMed  Google Scholar 

  101. Viscoli C, Herbrecht R, Akan H, et al. An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients. J Antimicrob Chemother. 2009;64:1274–81.

    CAS  PubMed  Google Scholar 

  102. Pagano L, Caira M, Candoni A, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica. 2009;95(4):644–50.

    PubMed  Google Scholar 

  103. Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis. 2009;48:265–73.

    CAS  PubMed  Google Scholar 

  104. 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;84:571–8.

    PubMed  Google Scholar 

  105. 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;31:859–68.

    CAS  PubMed  Google Scholar 

  106. 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;44:1289–97.

    CAS  PubMed  Google Scholar 

  107. Caillot D, Casasnovas O, Bernard A, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol. 1997;15:139–47.

    CAS  PubMed  Google Scholar 

  108. 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.

    PubMed  Google Scholar 

  109. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N Engl J Med. 1991;324:654–62.

    CAS  PubMed  Google Scholar 

  110. Hadjiliadis D, Howell DN, Davis RD, et al. Anastomotic infections in lung transplant recipients. Ann Transplant. 2000;5:13–9.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  112. Palmer SM, Drew RH, Whitehouse JD, et al. Safety of aerosolized amphotericin B lipid complex in lung transplant recipients. Transplantation. 2001;72:545–8.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  114. Hagensee ME, Bauwens JE, Kjos B, Bowden RA. Brain abscess ­following marrow transplantation: experience at the Fred Hutchinson Cancer Research Center, 1984–1992. Clin Infect Dis. 1994;19:402–8.

    CAS  PubMed  Google Scholar 

  115. Vinas PC, King PK, Diaz FG. Spinal aspergillus osteomyelitis. Clin Infect Dis. 1999;28:1223–9.

    CAS  PubMed  Google Scholar 

  116. Mouas H, Lutsar I, Dupont B, et al. Voriconazole for invasive bone aspergillosis: a worldwide experience of 20 cases. Clin Infect Dis. 2005;40:1141–7.

    CAS  PubMed  Google Scholar 

  117. Reis LJ, Barton TD, Pochettino A, et al. Successful treatment of Aspergillus prosthetic valve endocarditis with oral voriconazole. Clin Infect Dis. 2005;41:752–3.

    PubMed  Google Scholar 

  118. Halpern M, Szabo S, Hochberg E, et al. Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome. Am J Med. 1992;92:437–40.

    CAS  PubMed  Google Scholar 

  119. Rahimi F, Hashemian MN, Rajabi MT. Aspergillus fumigatus ­keratitis after laser in situ keratomileusis: a case report and review of post-LASIK fungal keratitis. Eye (Lond). 2007;21:843–5.

    CAS  Google Scholar 

  120. Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ. Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol. 2007;143:151–3.

    CAS  PubMed  Google Scholar 

  121. 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;46:1813–21.

    PubMed  Google Scholar 

  122. Dixon DM, Polak-Wyss A. The medically important dematiaceous fungi and their identification. Mycoses. 1991;34:1–18.

    CAS  PubMed  Google Scholar 

  123. Kaufman L, Standard PG, Jalbert M, Cole GT. Immunohistologic identification of Aspergillus spp. and other hyaline fungi by using polyclonal fluorescent antibodies. J Clin Microbiol. 1997;35:2206–9.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  125. 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;46:1032–7.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  127. Mosquera J, Denning DW. Azole cross-resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2002;46:556–7.

    CAS  PubMed  Google Scholar 

  128. Snelders E, van der Lee HA, Kuijpers J, et al. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 2008;5:e219.

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  131. Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood. 2001;97:1604–10.

    CAS  PubMed  Google Scholar 

  132. Herbrecht R, Letscher-Bru V, Oprea C, et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol. 2002;20:1898–906.

    PubMed  Google Scholar 

  133. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis. 2004;190:641–9.

    CAS  PubMed  Google Scholar 

  134. Maertens J, Theunissen K, Verbeken E, et al. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol. 2004;126:852–60.

    CAS  PubMed  Google Scholar 

  135. Mennink-Kersten MA, Klont RR, Warris A, Op den Camp HJ, Verweij PE. Bifidobacterium lipoteichoic acid and false ELISA reactivity in Aspergillus antigen detection. Lancet. 2004;363:325–7.

    CAS  PubMed  Google Scholar 

  136. Viscoli C, Machetti M, Cappellano P, et al. False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. Clin Infect Dis. 2004;38:913–6.

    PubMed  Google Scholar 

  137. Wheat LJ, Hackett E, Durkin M, et al. Histoplasmosis-associated cross-reactivity in the BioRad Platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol. 2007;14:638–40.

    CAS  PubMed  Google Scholar 

  138. Viscoli C, Machetti M, Gazzola P, et al. Aspergillus galactomannan antigen in the cerebrospinal fluid of bone marrow transplant recipients with probable cerebral aspergillosis. J Clin Microbiol. 2002;40:1496–9.

    CAS  PubMed  Google Scholar 

  139. Klont RR, Mennink-Kersten MA, Verweij PE. Utility of Aspergillus antigen detection in specimens other than serum specimens. Clin Infect Dis. 2004;39:1467–74.

    PubMed  Google Scholar 

  140. Becker MJ, Lugtenburg EJ, Cornelissen JJ, Van Der Schee C, Hoogsteden HC, De Marie S. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol. 2003;121:448–57.

    CAS  PubMed  Google Scholar 

  141. 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;42:5517–22.

    CAS  PubMed  Google Scholar 

  142. Bergeron A, Belle A, Sulahian A, et al. Contribution of galactomannan antigen detection in bronchoalveolar lavage to the diagnosis of invasive pulmonary aspergillosis in patients with hematologic malignancies. Chest 2009. 2010;137:410–5.

    Google Scholar 

  143. 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;15:1760–3.

    CAS  PubMed  Google Scholar 

  144. Hage CA, Reynolds JM, Durkin M, Wheat LJ, Knox KS. Plasmalyte as a cause of false-positive results for Aspergillus galactomannan in bronchoalveolar lavage fluid. J Clin Microbiol. 2007;45:676–7.

    PubMed  Google Scholar 

  145. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1–  >  3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis. 2005;41:654–9.

    CAS  PubMed  Google Scholar 

  146. Parker Jr JC, McCloskey JJ, Knauer KA. Pathobiologic features of human candidiasis: a common deep mycosis of the brain, heart and kidney in the altered host. J Clin Pathol. 1976;5:991–1000.

    Google Scholar 

  147. Senn L, Robinson JO, Schmidt 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;46:878–85.

    CAS  PubMed  Google Scholar 

  148. Obayashi T, Negishi K, Suzuki T, Funata N. Reappraisal of the serum (1–  >  3)-beta-D-glucan assay for the diagnosis of invasive fungal infections–a study based on autopsy cases from 6 years. Clin Infect Dis. 2008;46:1864–70.

    CAS  PubMed  Google Scholar 

  149. White PL, Linton CJ, Perry MD, Johnson EM, Barnes RA. The evolution and evaluation of a whole blood polymerase chain reaction assay for the detection of invasive aspergillosis in hematology patients in a routine clinical setting. Clin Infect Dis. 2006;42:479–86.

    CAS  PubMed  Google Scholar 

  150. Loeffler J, Hebart H, Brauchle U, Schumacher U, Einsele H. Comparison between plasma and whole blood specimens for detection of Aspergillus DNA by PCR. J Clin Microbiol. 2000;38:3830–3.

    CAS  PubMed  Google Scholar 

  151. Donnelly JP. Polymerase chain reaction for diagnosing invasive aspergillosis: getting closer but still a ways to go. Clin Infect Dis. 2006;42:487–9.

    CAS  PubMed  Google Scholar 

  152. Mengoli C, Cruciani M, Barnes RA, Loeffler J, Donnelly JP. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis. 2009;9:89–96.

    CAS  PubMed  Google Scholar 

  153. Cuenca-Estrella M, Meije Y, Diaz-Pedroche C, et al. Value of serial quantification of fungal DNA by a real-time PCR-based technique for early diagnosis of invasive Aspergillosis in patients with febrile neutropenia. J Clin Microbiol. 2009;47:379–84.

    CAS  PubMed  Google Scholar 

  154. Costa C, Costa JM, Desterke C, Botterel F, Cordonnier C, Bretagne S. Real-time PCR coupled with automated DNA extraction and detection of galactomannan antigen in serum by enzyme-linked immunosorbent assay for diagnosis of invasive aspergillosis. J Clin Microbiol. 2002;40:2224–7.

    CAS  PubMed  Google Scholar 

  155. Patterson TF. New agents for treatment of invasive aspergillosis. Clin Infect Dis. 2002;35:367–9.

    PubMed  Google Scholar 

  156. 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;44:2–12.

    CAS  PubMed  Google Scholar 

  157. Thompson GR 3rd, Rinaldi MG, Pennick G, Dorsey SA, Patterson TF, Lewis 2nd JS. Posaconazole therapeutic drug monitoring: a reference laboratory experience. Antimicrob Agents Chemother. 2009;53:2223–4.

    CAS  PubMed  Google Scholar 

  158. 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.

    CAS  PubMed  Google Scholar 

  159. Warn PA, Sharp A, Denning DW. In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp. J Antimicrob Chemother. 2006;57:135–8.

    CAS  PubMed  Google Scholar 

  160. Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin Infect Dis. 2001;32:686–93.

    CAS  PubMed  Google Scholar 

  161. Wingard JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis. 1999;29:1402–7.

    CAS  PubMed  Google Scholar 

  162. 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;26:1383–96.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  164. 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.

    PubMed  Google Scholar 

  165. Pfaller MA, Boyken L, Hollis RJ, et al. In vitro susceptibility of clinical isolates of Aspergillus spp. to anidulafungin, caspofungin, and micafungin: a head-to-head comparison using the CLSI M38-A2 broth microdilution method. J Clin Microbiol. 2009;47:3323–5.

    CAS  PubMed  Google Scholar 

  166. Spreghini E, Orlando F, Santinelli A, et al. Anidulafungin in combination with amphotericin B against Aspergillus fumigatus. Antimicrob Agents Chemother. 2009;53:4035–9.

    CAS  PubMed  Google Scholar 

  167. Espinel-Ingroff A, Johnson E, Hockey H, Troke P. Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies. J Antimicrob Chemother. 2008;61:616–20.

    CAS  PubMed  Google Scholar 

  168. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis. 2002;34:563–71.

    CAS  PubMed  Google Scholar 

  169. 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.

    CAS  PubMed  Google Scholar 

  170. Walsh TJ, Lutsar I, Driscoll T, et al. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J. 2002;21:240–8.

    PubMed  Google Scholar 

  171. Dodds Ashley ES, Lewis R, Lewis JS, Martin C, Andes D. Pharmacology of systemic antifungal agents. Clin Infect Dis. 2006;43:S29–39.

    Google Scholar 

  172. Smith J, Safdar N, Knasinski V, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006;50:1570–2.

    CAS  PubMed  Google Scholar 

  173. Walsh TJ, Karlsson MO, Driscoll T, et al. Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob Agents Chemother. 2004;48:2166–72.

    CAS  PubMed  Google Scholar 

  174. Barrett JP, Vardulaki KA, Conlon C, et al. A systematic review of the antifungal effectiveness and tolerability of amphotericin B formulations. Clin Ther. 2003;25:1295–320.

    CAS  PubMed  Google Scholar 

  175. 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;46:2564–8.

    CAS  PubMed  Google Scholar 

  176. Petraitis V, Petraitiene R, Groll AH, 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;46:1857–69.

    CAS  PubMed  Google Scholar 

  177. Bowman JC, Hicks PS, Kurtz MB, et al. The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro. Antimicrob Agents Chemother. 2002;46:3001–12.

    CAS  PubMed  Google Scholar 

  178. Schaffner A, Frick PG. The effect of ketoconazole on amphotericin B in a model of disseminated aspergillosis. J Infect Dis. 1985;151:902–10.

    CAS  PubMed  Google Scholar 

  179. Meletiadis J, Stergiopoulou T, O’Shaughnessy EM, Peter J, Walsh TJ. Concentration-dependent synergy and antagonism within a triple antifungal drug combination against Aspergillus species: analysis by a new response surface model. Antimicrob Agents Chemother. 2007;51:2053–64.

    CAS  PubMed  Google Scholar 

  180. Steinbach WJ, Stevens DA, Denning DW. Combination and sequential antifungal therapy for invasive aspergillosis: review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001. Clin Infect Dis. 2003;37 Suppl 3:S188–224.

    CAS  PubMed  Google Scholar 

  181. 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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  183. Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348:2416–22.

    CAS  PubMed  Google Scholar 

  184. Rijnders BJ, Cornelissen JJ, Slobbe L, 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;46:1401–8.

    CAS  PubMed  Google Scholar 

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Patterson, T.F. (2011). Aspergillosis. In: Kauffman, C., Pappas, P., Sobel, J., Dismukes, W. (eds) Essentials of Clinical Mycology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6640-7_14

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