Skip to main content
SpringerLink
Log in

Aspergillosis

  • Chapter
  • First Online:
Diagnosis and Treatment of Fungal Infections

  • 444 Accesses

Abstract

Aspergillosis is caused by Aspergillus, a hyaline mold responsible not only for invasive aspergillosis but also a variety of noninvasive or semi-invasive conditions. These syndromes range from colonization to allergic responses to Aspergillus, including allergic bronchopulmonary aspergillosis (ABPA), to semi-invasive or invasive infections, spanning a spectrum from chronic necrotizing pneumonia to invasive pulmonary aspergillosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thompson GR III, Patterson TF. Chapter 257. Aspergillus species. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, vol. 2. 9th ed. Philadelphia, PA: Elsevier; 2020. p. 3103–16.

    Google Scholar 

  2. 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:e1–e60.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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;387:760–9.

    Article  CAS  PubMed  Google Scholar 

  5. Maertens JA, Rahav G, Lee DG, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021;397:499–509.

    Article  CAS  PubMed  Google Scholar 

  6. Fang FC, Schooley RT. Treatment of COVID-19 - evidence-based or personalized medicine? Clin Infect Dis. 2020;74:149. https://doi.org/10.1093/cid/ciaa996.

    Article  CAS  Google Scholar 

  7. Thompson GR III, Cornely OA, Pappas PG, et al. Invasive aspergillosis as an under-recognized superinfection in COVID-19. Open Forum Infect Dis. 2020;7:ofaa242.

    Article  Google Scholar 

  8. Cadena J, Thompson GR 3rd, Patterson TF. Aspergillosis: epidemiology, diagnosis, and treatment. Infect Dis Clin N Am. 2021;35:415–34.

    Article  Google Scholar 

  9. Davis MR, Thompson GR 3rd, Patterson TF. Fungal infections potentiated by biologics. Infect Dis Clin N Am. 2020;34:389–411.

    Article  Google Scholar 

  10. Woodcock AA, Steel N, Moore CB, Howard SJ, Custovic A, Denning DW. Fungal contamination of bedding. Allergy. 2006;61:140–2.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus study group. Medicine. 2000;79:250–60.

    Article  CAS  PubMed  Google Scholar 

  14. Hajjeh RA, Warnock DW. Counterpoint: Invasive aspergillosis and the environment—rethinking our approach to prevention. Clin Infect Dis. 2001;33:1549–52.

    Article  CAS  PubMed  Google Scholar 

  15. Thompson GR 3rd, Young JH. Aspergillus infections. N Engl J Med. 2021;385:1496–509.

    Article  CAS  PubMed  Google Scholar 

  16. Anaissie EJ, Stratton SL, Dignani MC, et al. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies. Blood. 2003;101:2542–6.

    Article  CAS  PubMed  Google Scholar 

  17. Iwen PC, Rupp ME, Langnas AN, Reed EC, Hinrichs SH. Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature. Clin Infect Dis. 1998;26:1092–7.

    Article  CAS  PubMed  Google Scholar 

  18. Vidal-Acuna MR, Ruiz-Perez de Pipaon M, Torres-Sanchez MJ, Aznar J. Identification of clinical isolates of Aspergillus, including cryptic species, by matrix assisted laser desorption ionization time-of-flight mass spectrometry (maldi-tof ms). Med Mycol. 2018;56:838–46.

    Article  CAS  PubMed  Google Scholar 

  19. Siqueira JPZ, Wiederhold N, Gene J, Garcia D, Almeida MTG, Guarro J. Cryptic Aspergillus from clinical samples in the USA and description of a new species in section flavipedes. Mycoses. 2018;61:814–25.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  21. Maertens J, Vrebos M, Boogaerts M. Assessing risk factors for systemic fungal infections. Eur J Cancer Care. 2001;10:56–62.

    Article  CAS  Google Scholar 

  22. Ghez D, Calleja A, Protin C, et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood. 2018;131:1955–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. Blot SI, Taccone FS, Van den Abeele AM, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2012;186:56–64.

    Article  PubMed  Google Scholar 

  25. Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis. 2007;45:205–16.

    Article  PubMed  Google Scholar 

  26. Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother. 2017;72:i39–47.

    Article  CAS  PubMed  Google Scholar 

  27. Wauters J, Baar I, Meersseman P, et al. Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study. Intensive Care Med. 2012;38:1761–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Crum-Cianflone NF. Invasive aspergillosis associated with severe influenza infections. Open forum. Infect Dis. 2016;3:ofw171.

    Google Scholar 

  29. van de Veerdonk FL, Kolwijck E, Lestrade PP, et al. Influenza-associated aspergillosis in critically ill patients. Am J Respir Crit Care Med. 2017;196:524–7.

    Article  PubMed  Google Scholar 

  30. Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21:e149–e62.

    Article  CAS  PubMed  Google Scholar 

  31. Schauwvlieghe A, Rijnders BJA, Philips N, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6:782–92.

    Article  PubMed  Google Scholar 

  32. White PL, Dhillon R, Cordey A, et al. A national strategy to diagnose coronavirus disease 2019-associated invasive fungal disease in the intensive care unit. Clin Infect Dis. 2021;73:e1634–e44.

    Article  CAS  PubMed  Google Scholar 

  33. Prattes J, Koehler P, Hoenigl M, Group E-CS. Covid-19 associated pulmonary aspergillosis: regional variation in incidence and diagnostic challenges. Intensive Care Med. 2021;47:1339–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Verweij PE, Bruggemann RJM, Azoulay E, et al. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis. Intensive Care Med. 2021;47:819–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. van der Linden JW, Camps SM, Kampinga GA, et al. Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles. Clin Infect Dis. 2013;57:513–20.

    Article  PubMed  Google Scholar 

  36. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Heo ST, Tatara AM, Jimenez-Ortigosa C, et al. Changes in in vitro susceptibility patterns of Aspergillus to triazoles and correlation with aspergillosis outcome in a tertiary care cancer center, 1999-2015. Clin Infect Dis. 2017;65:216–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Glampedakis E, Coste AT, Aruanno M, et al. Efficacy of antifungal monotherapies and combinations against Aspergillus calidoustus. Antimicrob Agents Chemother. 2018;62:466–9.

    Article  Google Scholar 

  39. Egli A, Fuller J, Humar A, et al. Emergence of Aspergillus calidoustus infection in the era of posttransplantation azole prophylaxis. Transplantation. 2012;94:403–10.

    Article  PubMed  Google Scholar 

  40. Camps SM, Rijs AJ, Klaassen CH, et al. Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism. J Clin Microbiol. 2012;50:2674–80.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wiederhold NP, Gil VG, Gutierrez F, et al. First detection of TR34 L98H and TR46 Y121F t289a cyp51 mutations in Aspergillus fumigatus isolates in the United States. J Clin Microbiol. 2016;54:168–71.

    Article  CAS  PubMed  Google Scholar 

  42. Wiederhold NP, Verweij PE. Aspergillus fumigatus and pan-azole resistance: who should be concerned? Curr Opin Infect Dis. 2020;33:290–7.

    Article  CAS  PubMed  Google Scholar 

  43. Snelders E, Camps SM, Karawajczyk A, et al. Genotype-phenotype complexity of the TR46/Y121F/T289A cyp51a azole resistance mechanism in Aspergillus fumigatus. Fungal Genet Biol. 2015;82:129–35.

    Article  CAS  PubMed  Google Scholar 

  44. Buil JB, Snelders E, Denardi LB, Melchers WJG, Verweij PE. Trends in azole resistance in Aspergillus fumigatus, The Netherlands, 1994-2016. Emerg Infect Dis. 2019;25:176–8.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 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;188:305–19.

    Article  CAS  PubMed  Google Scholar 

  46. Brummer E, Kamberi M, Stevens DA. Regulation by granulocyte-macrophage colony-stimulating factor and/or steroids given in vivo of proinflammatory cytokine and chemokine production by bronchoalveolar macrophages in response to Aspergillus conidia. J Infect Dis. 2003;187:705–9.

    Article  CAS  PubMed  Google Scholar 

  47. Kan VL, Bennett JE. Lectin-like attachment sites on murine pulmonary alveolar macrophages bind Aspergillus fumigatus conidia. J Infect Dis. 1988;158:407–14.

    Article  CAS  PubMed  Google Scholar 

  48. 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.

    Article  CAS  PubMed  Google Scholar 

  49. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Latge JP, Chamilos G. Aspergillus fumigatus and aspergillosis in 2019. Clin Microbiol Rev. 2019;33:e00140.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Stanzani M, Orciuolo E, Lewis R, et al. Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes. Blood. 2005;105:2258–65.

    Article  CAS  PubMed  Google Scholar 

  52. Chai LY, Kullberg BJ, Vonk AG, et al. Modulation of toll-like receptor 2 (tlr2) and tlr4 responses by Aspergillus fumigatus. Infect Immun. 2009;77:2184–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  55. 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.

    Article  PubMed  Google Scholar 

  56. Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev. 2004;2004:Cd001108.

    PubMed  PubMed Central  Google Scholar 

  57. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  59. Gillespie MB, O’Malley BW. An algorithmic approach to the diagnosis and management of invasive fungal rhinosinusitis in the immunocompromised patient. Otolaryngol Clin N Am. 2000;33:323–34.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  62. Torres-Rodríguez JM, Madrenys-Brunet N, Siddat M, López-Jodra O, Jimenez T. Aspergillus versicolor as cause of onychomycosis: report of 12 cases and susceptibility testing to antifungal drugs. J Eur Acad Dermatol Venereol. 1998;11:25–31.

    Article  PubMed  Google Scholar 

  63. Kuo IC, Margolis TP, Cevallos V, Hwang DG. Aspergillus fumigatus keratitis after laser in situ keratomileusis. Cornea. 2001;20:342–4.

    Article  CAS  PubMed  Google Scholar 

  64. 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.

    Article  PubMed  Google Scholar 

  65. Jain LR, Denning DW. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J Infect. 2006;52:e133–7.

    Article  PubMed  Google Scholar 

  66. 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.

    Article  CAS  PubMed  Google Scholar 

  67. 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.

    Article  PubMed  Google Scholar 

  68. Miller WT Jr, Sais GJ, Frank I, Gefter WB, Aronchick JM, Miller WT. Pulmonary aspergillosis in patients with aids. Clinical and radiographic correlations. Chest. 1994;105:37–44.

    Article  PubMed  Google Scholar 

  69. Patterson TF. Advances and challenges in management of invasive mycoses. Lancet. 2005;366:1013–25.

    Article  PubMed  Google Scholar 

  70. Allo MD, Miller J, Townsend T, Tan C. Primary cutaneous aspergillosis associated with Hickman intravenous catheters. N Engl J Med. 1987;317:1105–8.

    Article  CAS  PubMed  Google Scholar 

  71. Mylonakis E, Rich J, Skolnik PR, De Orchis DF, Flanigan T. Invasive Aspergillus sinusitis in patients with human immunodeficiency virus infection. Report of 2 cases and review. Medicine (Baltimore). 1997;76:249–55.

    Article  CAS  PubMed  Google Scholar 

  72. Ellis ME, Al-Abdely H, Sandridge A, Greer W, Ventura W. Fungal endocarditis: evidence in the world literature, 1965-1995. Clin Infect Dis. 2001;32:50–62.

    Article  CAS  PubMed  Google Scholar 

  73. Denning DW, Stevens DA. Antifungal and surgical treatment of invasive aspergillosis: review of 2,121 published cases. Rev Infect Dis. 1990;12:1147–201.

    Article  CAS  PubMed  Google Scholar 

  74. Ceesay MM, Desai SR, Berry L, et al. A comprehensive diagnostic approach using galactomannan, targeted beta-d-glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients. Br J Haematol. 2015;168:219–29.

    Article  CAS  PubMed  Google Scholar 

  75. Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71:1367–76.

    Article  PubMed  Google Scholar 

  76. Sangoi AR, Rogers WM, Longacre TA, Montoya JG, Baron EJ, Banaei N. Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic specimens: a ten-year retrospective review at a single institution. Am J Clin Pathol. 2009;131:364–75.

    Article  PubMed  Google Scholar 

  77. Shah AA, Hazen KC. Diagnostic accuracy of histopathologic and cytopathologic examination of Aspergillus species. Am J Clin Pathol. 2013;139:55–61.

    Article  PubMed  Google Scholar 

  78. Sutton DA, Fothergill AW, Rinaldi MG. Guide to clinically significant fungi. Baltimore: Williams & Wilkins; 1998.

    Google Scholar 

  79. Verweij PE, Ananda-Rajah M, Andes D, et al. International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus. Drug Resist Updat. 2015;21-22:30–40.

    Article  PubMed  Google Scholar 

  80. 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;50:1258–63.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 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.

    Article  CAS  PubMed  Google Scholar 

  82. Herbrecht R. Improving the outcome of invasive aspergillosis: new diagnostic tools and new therapeutic strategies. Ann Hematol. 2002;81(Suppl 2):S52–3.

    CAS  PubMed  Google Scholar 

  83. 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;49:1688–93.

    Article  PubMed  Google Scholar 

  84. Duarte RF, Sanchez-Ortega I, Cuesta I, et al. Serum galactomannan-based early detection of invasive aspergillosis in hematology patients receiving effective antimold prophylaxis. Clin Infect Dis. 2014;59:1696–702.

    Article  CAS  PubMed  Google Scholar 

  85. Maertens J, Buve K, Theunissen K, et al. Galactomannan serves as a surrogate endpoint for outcome of pulmonary invasive aspergillosis in neutropenic hematology patients. Cancer. 2009;115:355–62.

    Article  PubMed  Google Scholar 

  86. Mercier T, Guldentops E, Lagrou K, Maertens J. Galactomannan, a surrogate marker for outcome in invasive aspergillosis: finally coming of age. Front Microbiol. 2018;9:661.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Neofytos D, Railkar R, Mullane KM, et al. Correlation between circulating fungal biomarkers and clinical outcome in invasive aspergillosis. PLoS One. 2015;10:e0129022.

    Article  PubMed  PubMed Central  Google Scholar 

  88. White PL, Bretagne S, Klingspor L, et al. Aspergillus PCR: one step closer to standardization. J Clin Microbiol. 2010;48:1231–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. White PL, Bretagne S, Caliendo AM, et al. Aspergillus polymerase chain reaction-an update on technical recommendations, clinical applications, and justification for inclusion in the second revision of the eortc/msgerc definitions of invasive fungal disease. Clin Infect Dis. 2021;72:S95–S101.

    Article  CAS  PubMed  Google Scholar 

  90. White PL, Wingard JR, Bretagne S, et al. Aspergillus polymerase chain reaction: systematic review of evidence for clinical use in comparison with antigen testing. Clin Infect Dis. 2015;61:1293–303.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Chong GM, van der Beek MT, von dem Borne PA, et al. Pcr-based detection of Aspergillus fumigatus cyp51a mutations on bronchoalveolar lavage: a multicentre validation of the aspergenius assay(r) in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother. 2016;71:3528–35.

    Article  CAS  PubMed  Google Scholar 

  92. Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-d-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis. 2004;39:199–205.

    Article  CAS  PubMed  Google Scholar 

  93. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  95. Mennink-Kersten MA, Verweij PE. Non-culture-based diagnostics for opportunistic fungi. Infect Dis Clin North Am. 2006;20:711–27. viii

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  98. Keating GM. Posaconazole. Drugs. 2005;65:1553–67; discussion 68–9.

    Article  CAS  PubMed  Google Scholar 

  99. Nguyen MH, Davis MR, Wittenberg R, et al. Posaconazole serum drug levels associated with pseudohyperaldosteronism. Clin Infect Dis. 2020;70:2593–8.

    Article  CAS  PubMed  Google Scholar 

  100. Walsh TJ, Goodman JL, Pappas P, et al. Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin b (ambisome) in patients infected with Aspergillus species and other filamentous fungi: maximum tolerated dose study. Antimicrob Agents Chemother. 2001;45:3487–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. 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.

    Article  CAS  PubMed  Google Scholar 

  102. 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.

    Article  CAS  PubMed  Google Scholar 

  103. 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  PubMed Central  Google Scholar 

  104. Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162:81–9.

    Article  PubMed  Google Scholar 

  105. Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1–e38.

    Article  PubMed  Google Scholar 

  106. Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433–44.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Vadnerkar A, Nguyen MH, Mitsani D, et al. Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant. 2010;29:1240–4.

    Article  PubMed  Google Scholar 

  108. Zwald FO, Spratt M, Lemos BD, et al. Duration of voriconazole exposure: an independent risk factor for skin cancer after lung transplantation. Dermatol Surg. 2012;38:1369–74.

    Article  CAS  PubMed  Google Scholar 

  109. Wermers RA, Cooper K, Razonable RR, et al. Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy. Clin Infect Dis. 2011;52:604–11.

    Article  CAS  PubMed  Google Scholar 

  110. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008;46:201–11.

    Article  CAS  PubMed  Google Scholar 

  111. 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;55:1080–7.

    Article  CAS  PubMed  Google Scholar 

  112. Thompson GR 3rd, Lewis P, Mudge S, Patterson TF, Burnett BP. Open-label crossover oral bioequivalence pharmacokinetics comparison for a 3-day loading dose regimen and 15-day steady-state administration of SUBA-itraconazole and conventional itraconazole capsules in healthy adults. Antimicrob Agents Chemother. 2020;64:e00400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Miceli MH, Kauffman CA. Isavuconazole: a new broad-spectrum triazole antifungal agent. Clin Infect Dis. 2015;61:1558–65.

    Article  CAS  PubMed  Google Scholar 

  114. 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.

    Article  CAS  PubMed  Google Scholar 

  115. Jung DS, Tverdek FP, Kontoyiannis DP. Switching from posaconazole suspension to tablets increases serum drug levels in leukemia patients without clinically relevant hepatotoxicity. Antimicrob Agents Chemother. 2014;58:6993–5.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Davis MR, Nguyen MH, Gintjee TJ, Odermatt A, Young BY, Thompson GR. Management of posaconazole-induced pseudohyperaldosteronism. J Antimicrob Chemother. 2020;75:3688–93.

    Article  CAS  PubMed  Google Scholar 

  117. Thompson GR 3rd, Beck KR, Patt M, Kratschmar DV, Odermatt A. Posaconazole-induced hypertension due to inhibition of 11-beta-hydroxylase and 11beta-hydroxysteroid dehydrogenase 2. J Endocr Soc. 2019;3:1361–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Thompson GR 3rd, Chang D, Wittenberg RR, McHardy I, Semrad A. In vivo 11-beta-hydroxysteroid dehydrogenase inhibition in posaconazole-induced hypertension and hypokalemia. Antimicrob Agents Chemother. 2017;61:e00760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chin A, Pergam SA, Fredricks DN, Hoofnagle AN, Baker KK, Jain R. Evaluation of posaconazole serum concentrations from delayed-release tablets in patients at high risk for fungal infections. Antimicrob Agents Chemother. 2017;61:e00569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Rex JH, Walsh TJ, Nettleman M, et al. Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses. Clin Infect Dis. 2001;33:95–106.

    Article  CAS  PubMed  Google Scholar 

  121. 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.

    Article  CAS  PubMed  Google Scholar 

  122. Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharmacokinetics, safety and efficacy. Drugs. 2004;64:1997–2020.

    Article  CAS  PubMed  Google Scholar 

  123. 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;39:1407–16.

    Article  PubMed  Google Scholar 

  124. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  126. Aliff TB, Maslak PG, Jurcic JG, et al. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer. 2003;97:1025–32.

    Article  CAS  PubMed  Google Scholar 

  127. Kontoyiannis DP, Hachem R, Lewis RE, et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin b as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003;98:292–9.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  129. 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  CAS  PubMed  Google Scholar 

  130. 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  CAS  PubMed  Google Scholar 

  131. Morrissey CO, Chen SC, Sorrell TC, et al. Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial. Lancet Infect Dis. 2013;13:519–28.

    Article  CAS  PubMed  Google Scholar 

  132. 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.

    Article  CAS  PubMed  Google Scholar 

  133. Patterson TF, Boucher HW, Herbrecht R, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  134. Maschmeyer G, Patterson TF. Our 2014 approach to breakthrough invasive fungal infections. Mycoses. 2014;57:645–51.

    Article  PubMed  Google Scholar 

Further Reading

  • Bassetti M, Bouza E. Invasive mould infections in the ICU setting: complexities and solutions. J Antimicrob Chemother. 2017;72:i39–47.

    Article  CAS  PubMed  Google Scholar 

  • Buil JB, Snelders E, Denardi LB, Melchers WJG, Verweij PE. Trends in azole resistance in Aspergillus fumigatus, The Netherlands, 1994-2016. Emerg Infect Dis. 2019;25:176–8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis MR, Thompson GR 3rd, Patterson TF. Fungal infections potentiated by biologics. Infect Dis Clin N Am. 2020;34:389–411.

    Article  Google Scholar 

  • Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis. 2020;71:1367–76.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing covid-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. 2021;21:e149–e62.

    Article  CAS  PubMed  Google Scholar 

  • Latge JP, Chamilos G. Aspergillus fumigatus and aspergillosis in 2019. Clin Microbiol Rev. 2019;33:e00140.

    Article  PubMed  PubMed Central  Google Scholar 

  • 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;387:760–9.

    Article  CAS  PubMed  Google Scholar 

  • Maertens JA, Rahav G, Lee DG, et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021;397:499–509.

    Article  CAS  PubMed  Google Scholar 

  • Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162:81–9.

    Article  PubMed  Google Scholar 

  • 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:e1–e60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson GR 3rd, Young JH. Aspergillus infections. N Engl J Med. 2021;385:1496–509.

    Article  CAS  PubMed  Google Scholar 

  • Thompson GR III, Patterson TF. Chapter 257. Aspergillus species. In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases, vol. 2. 9th ed. Philadelphia, PA: Elsevir; 2020. p. 3103–16.

    Google Scholar 

  • Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1–e38.

    Article  PubMed  Google Scholar 

  • Wiederhold NP, Verweij PE. Aspergillus fumigatus and pan-azole resistance: who should be concerned? Curr Opin Infect Dis. 2020;33:290–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA

    Helen W. Boucher

  2. Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA

    Thomas F. Patterson

Authors
  1. Helen W. Boucher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas F. Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas F. Patterson .

Editor information

Editors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Duane R. Hospenthal

  2. Departments of Pathology, Microbiology, and Clinical Laboratory Sciences, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Michael G. Rinaldi

  3. Departments of Medicine and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

    Thomas J. Walsh

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Boucher, H.W., Patterson, T.F. (2023). Aspergillosis. In: Hospenthal, D.R., Rinaldi, M.G., Walsh, T.J. (eds) Diagnosis and Treatment of Fungal Infections. Springer, Cham. https://doi.org/10.1007/978-3-031-35803-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-35803-6_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-35802-9

  • Online ISBN: 978-3-031-35803-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation