Skip to main content
SpringerLink
Log in

Emerging Fungal Infections

  • Chapter
  • First Online:
Pulmonary Involvement in Patients with Hematological Malignancies

Abstract

Emerging fungal pathogens have been increasingly reported as causes of pneumonia in severely immunocompromised patients. These include Fusarium species, Zygomycetes, the agents of phaeohyphomycosis and non-fumigatus Aspergillus species. Hematologic patients at high risk to develop these infections are those with prolonged neutropenia and/or severe T-cell immunodeficiency, typically patients with acute leukemia receiving chemotherapy for induction of remission, allogeneic stem cell transplant recipients with acute or chronic graft versus host disease, patients with multiple myeloma receiving aggressive chemotherapy, and patients with lymphoproliferative disease receiving monoclonal antibodies such as alemtuzumab or purine analogs.

The emerging fungal pneumonias are challenging because they carry a very poor prognosis as a result of delays in the diagnosis, resistance to various antifungal drugs and by the fact that they occur in severely immunosuppressed patients. Therefore, early and correct diagnosis is critical. However, the clinical manifestations and radiologic picture of these emerging infections are usually nonspecific and overlap with that caused by Aspergillus fumigatus. Culture and histopathology remain the most important diagnostic tools, and antifungal susceptibility tests may help to select the appropriate antifungal agent.

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 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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. Anaissie EJ, Kontoyiannis DP, O’Brien S, Kantarjian H, Robertson L, Lerner S, Keating MJ (1998) Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med 129:559–566

    PubMed  CAS  Google Scholar 

  2. Asai K, Suzuki K, Takahashi T, Ito Y, Kazui T, Kita Y (2003) Pulmonary resection with chest wall removal and reconstruction for invasive pulmonary mucormycosis during antileukemia chemotherapy. Jpn J Thorac Cardiovasc Surg 51:163–166

    Article  PubMed  Google Scholar 

  3. Bakshi NA, Volk EE (2001) Pulmonary mucormycosis diagnosed by fine needle aspiration cytology. A case report. Acta Cytol 45:411–414

    Article  PubMed  CAS  Google Scholar 

  4. Balajee SA, Gribskov JL, Hanley E, Nickle D, Marr KA (2005) Aspergillus lentulus sp. nov., a new sibling species of A. fumigatus. Eukaryot Cell 4:625–632

    Article  PubMed  CAS  Google Scholar 

  5. Balajee SA, Weaver M, Imhof A, Gribskov J, Marr KA (2004) Aspergillus fumigatus variant with decreased susceptibility to multiple antifungals. Antimicrob Agents Chemother 48:1197–1203

    Article  PubMed  CAS  Google Scholar 

  6. Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP (2009) Phaeohyphomycosis in a tertiary care cancer center. Clin Infect Dis 48:1033–1041

    Article  PubMed  Google Scholar 

  7. Bouza E, Munoz P (2004) Invasive infections caused by Blastoschizomyces capitatus and Scedosporium spp. Clin Microbiol Infect 10(Suppl 1):76–85

    Article  PubMed  Google Scholar 

  8. Bulpa P, Dive A, Sibille Y (2007) Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J 30:782–800

    Article  PubMed  CAS  Google Scholar 

  9. Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP (2005) Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis 41:60–66

    Article  PubMed  Google Scholar 

  10. Daly A, McAfee S, Dey B, Colby C, Schulte L, Yeap B, Sackstein R, Tarbell NJ, Sachs D, Sykes M, Spitzer TR (2003) Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant 9:373–382

    Article  PubMed  Google Scholar 

  11. Espinel-Ingroff A, Johnson E, Hockey H, Troke P (2008) 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 61:616–620

    Article  PubMed  CAS  Google Scholar 

  12. Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Martin PJ, Storb RF, Marr KA (2003) Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 102:827–833

    Article  PubMed  CAS  Google Scholar 

  13. Gonzalez CE, Rinaldi MG, Sugar AM (2002) Zygomycosis. Infect Dis Clin North Am 16:895–914, vi

    Article  PubMed  Google Scholar 

  14. Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, Herbrecht R, Langston A, Marr KA, Schiller G, Schuster M, Wingard JR, Gonzalez CE, Revankar SG, Corcoran G, Kryscio RJ, Hare R (2006) Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 50:126–133

    Article  PubMed  CAS  Google Scholar 

  15. Hachem RY, Kontoyiannis DP, Boktour MR, Afif C, Cooksley C, Bodey GP, Chatzinikolaou I, Perego C, Kantarjian HM, Raad II (2004) Aspergillus terreus: an emerging amphotericin B-resistant opportunistic mold in patients with hematologic malignancies. Cancer 101: 1594–1600

    Article  PubMed  Google Scholar 

  16. Hagen EA, Stern H, Porter D, Duffy K, Foley K, Luger S, Schuster SJ, Stadtmauer EA, Schuster MG (2003) High rate of invasive fungal infections following nonmyeloablative allogeneic transplantation. Clin Infect Dis 36:9–15

    Article  PubMed  Google Scholar 

  17. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415

    Article  PubMed  CAS  Google Scholar 

  18. Herbrecht R, Letscher-Bru V, Bowden RA, Kusne S, Anaissie EJ, Graybill JR, Noskin GA, Oppenheim BA, Andres E, Pietrelli LA (2001) Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 20:460–466

    Article  PubMed  CAS  Google Scholar 

  19. Imhof A, Balajee SA, Fredricks DN, Englund JA, Marr KA (2004) Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis 39: 743–746

    Article  PubMed  Google Scholar 

  20. Jahagirdar BN, Morrison VA (2002) Emerging fungal pathogens in patients with hematologic malignancies and marrow/stem-cell transplant recipients. Semin Respir Infect 17:113–120

    Article  PubMed  Google Scholar 

  21. Junghanss C, Marr KA, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Chauncey T, McSweeney PA, Storb R (2002) Incidence and outcome of bacterial and fungal infections following nonmyeloablative compared with myeloablative allogeneic hematopoietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 8: 512–520

    Article  PubMed  Google Scholar 

  22. Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR (2002) Therapeutic role of alemtuzumab (Campath-1 H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561

    Article  PubMed  CAS  Google Scholar 

  23. Labbe AC, Su SH, Laverdiere M, Pepin J, Patino C, Cohen S, Kiss T, Lachance S, Sauvageau G, Busque L, Roy DC, Roy J (2007) High incidence of invasive aspergillosis associated with intestinal graft-versus-host disease following nonmyeloablative transplantation. Biol Blood Marrow Transplant 13:1192–1200

    Article  PubMed  Google Scholar 

  24. Laros-van Gorkom BA, Huisman CA, Wijermans PW, Schipperus MR (2007) Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands. Neth J Med 65:333–338

    PubMed  CAS  Google Scholar 

  25. Lass-Florl C, Griff K, Mayr A, Petzer A, Gastl G, Bonatti H, Freund M, Kropshofer G, Dierich MP, Nachbaur D (2005) Epidemiology and outcome of infections due to Aspergillus terreus: 10-year single centre experience. Br J Haematol 131:201–207

    Article  PubMed  Google Scholar 

  26. Lee DG, Choi JH, Choi SM, Yoo JH, Kim YJ, Min CK, Lee S, Kim DW, Shin WS, Kim CC (2002) Two cases of disseminated mucormycosis in patients following allogeneic bone marrow transplantation. J Korean Med Sci 17: 403–406

    PubMed  Google Scholar 

  27. Losee JE, Selber J, Vega S, Hall C, Scott G, Serletti JM (2002) Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg 49:385–390

    Article  PubMed  Google Scholar 

  28. MacKenzie KM, Baumgarten KL, Helm BM, McFadden PM, Deduska NJ, Loss GE Jr, Eason JD (2002) Innovative medical management with resection for successful treatment of pulmonary mucormycosis despite diagnostic delay. J La State Med Soc 154:82–85

    PubMed  Google Scholar 

  29. Maertens J, Lagrou K, Deweerdt H, Surmont I, Verhoef GE, Verhaegen J, Boogaerts MA (2000) Disseminated infection by Scedosporium prolificans: an emerging fatality among haematology patients. Case report and review. Ann Hematol 79:340–344

    Article  PubMed  CAS  Google Scholar 

  30. Maertens J, Maertens V, Theunissen K, Meersseman W, Meersseman P, Meers S, Verbeken E, Verhoef G, Van EJ, Lagrou K (2009)) Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis 49: 1688–1693

    Article  Google Scholar 

  31. Marr KA, Carter RA, Boeckh M, Martin P, Corey L (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100:4358–4366

    Article  PubMed  CAS  Google Scholar 

  32. Marr KA, Carter RA, Crippa F, Wald A, Corey L (2002) Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 34:909–917

    Article  PubMed  Google Scholar 

  33. Marty FM, Lee SJ, Fahey MM, Alyea EP, Soiffer RJ, Antin JH, Baden LR (2003) Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study. Blood 102:2768–2776

    Article  PubMed  CAS  Google Scholar 

  34. Meersseman W, Lagrou K, Maertens J, Van WE (2007) Invasive aspergillosis in the intensive care unit. Clin Infect Dis 45:205–216

    Article  PubMed  Google Scholar 

  35. Nath DS, Kandaswamy R, Gruessner R, Sutherland DE, Dunn DL, Humar A (2005) Fungal infections in transplant recipients receiving alemtuzumab. Transplant Proc 37:934–936

    Article  PubMed  CAS  Google Scholar 

  36. Nelson PE, Dignani MC, Anaissie EJ (1994) Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev 7:479–504

    PubMed  CAS  Google Scholar 

  37. Nucci M (2003) Emerging moulds: Fusarium, Scedosporium and Zygomycetes in transplant recipients. Curr Opin Infect Dis 16:607–612

    Article  PubMed  Google Scholar 

  38. Nucci M, Anaissie E (2007) Fusarium infections in immunocompromised patients. Clin Microbiol Rev 20:695–704

    Article  PubMed  CAS  Google Scholar 

  39. Nucci M, Anaissie E (2002) Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management. Clin Infect Dis 35:909–920

    Article  PubMed  Google Scholar 

  40. Nucci M, Anaissie E (2006) Emerging fungi. Infect Dis Clin North Am 20:563–579

    Article  PubMed  Google Scholar 

  41. Nucci M, Anaissie E (2009) Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis 49:1211–1225

    Article  PubMed  CAS  Google Scholar 

  42. Nucci M, Anaissie EJ, Queiroz-Telles F, Martins CA, Trabasso P, Solza C, Mangini C, Simoes BP, Colombo AL, Vaz J, Levy CE, Costa S, Moreira VA, Oliveira JS, Paraguay N, Duboc G, Voltarelli JC, Maiolino A, Pasquini R, Souza CA (2003) Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer 98: 315–319

    Article  PubMed  Google Scholar 

  43. Nucci M, Marr KA (2005) Emerging fungal diseases. Clin Infect Dis 41:521–526

    Article  PubMed  Google Scholar 

  44. Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, Voltarelli JC, Colombo AL, Imhof A, Pasquini R, Maiolino A, Souza CA, Anaissie E (2004) Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis 38:1237–1242

    Article  PubMed  Google Scholar 

  45. Odabasi Z, Mattiuzzi G, Estey E, Kantarjian H, Saeki F, Ridge RJ, Ketchum PA, Finkelman MA, Rex JH, Ostrosky-Zeichner L (2004) 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 39:199–205

    Article  PubMed  CAS  Google Scholar 

  46. Panackal AA, Imhof A, Hanley EW, Marr KA (2006) Aspergillus ustus infections among transplant recipients. Emerg Infect Dis 12:403–408

    PubMed  Google Scholar 

  47. Pavie J, Lacroix C, Hermoso DG, Robin M, Ferry C, Bergeron A, Feuilhade M, Dromer F, Gluckman E, Molina JM, Ribaud P (2005) Breakthrough disseminated Aspergillus ustus infection in allogeneic hematopoietic stem cell transplant recipients receiving voriconazole or caspofungin prophylaxis. J Clin Microbiol 43: 4902–4904

    Article  PubMed  Google Scholar 

  48. Perfect JR, Cox GM, Lee JY, Kauffman CA, de Repentigny L, Chapman SW, Morrison VA, Pappas P, Hiemenz JW, Stevens DA (2001) The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin Infect Dis 33:1824–1833

    Article  PubMed  CAS  Google Scholar 

  49. Perfect JR, Marr KA, Walsh TJ, Greenberg RN, Dupont B, de la Torre-Cisneros J, Just-Nubling G, Schlamm HT, Lutsar I, Espinel-Ingroff A, Johnson E (2003) Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 36:1122–1131

    Article  PubMed  CAS  Google Scholar 

  50. Pfeiffer CD, Fine JP, Safdar N (2006) Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 42:1417–1427

    Article  PubMed  CAS  Google Scholar 

  51. Racil Z, Kocmanova I, Lengerova M, Winterova J, Mayer J (2007) Intravenous PLASMA-LYTE as a major cause of false-positive results of platelia Aspergillus test for galactomannan detection in serum. J Clin Microbiol 45: 3141–3142

    Article  PubMed  Google Scholar 

  52. Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG (2002) Disseminated phaeohyphomycosis: review of an emerging mycosis. Clin Infect Dis 34:467–476

    Article  PubMed  Google Scholar 

  53. Saracli MA, Mutlu FM, Yildiran ST, Kurekci AE, Gonlum A, Uysal Y, Erdem U, Basustaoglu AC, Sutton DA (2007) Clustering of invasive Aspergillus ustus eye infections in a tertiary care hospital: a molecular epidemiologic study of an uncommon species. Med Mycol 45:377–384

    Article  PubMed  CAS  Google Scholar 

  54. Schutt P, Brandhorst D, Stellberg W, Poser M, Ebeling P, Muller S, Buttkereit U, Opalka B, Lindemann M, Grosse-Wilde H, Seeber S, Moritz T, Nowrousian MR (2006) Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections. Leuk Lymphoma 47:1570–1582

    Article  PubMed  Google Scholar 

  55. Singh N (2002) Imaging findings in invasive zygomycosis. Liver Transpl 8:306–307

    Article  PubMed  Google Scholar 

  56. Siwek GT, Pfaller MA, Polgreen PM, Cobb S, Hoth P, Magalheas-Silverman M, Diekema DJ (2006) Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell transplant patients receiving voriconazole prophylaxis. Diagn Microbiol Infect Dis 55:209–212

    Article  PubMed  CAS  Google Scholar 

  57. Steinbach WJ, Benjamin DK Jr, Kontoyiannis DP, Perfect JR, Lutsar I, Marr KA, Lionakis MS, Torres HA, Jafri H, Walsh TJ (2004) Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin Infect Dis 39:192–198

    Article  PubMed  Google Scholar 

  58. Stergiopoulou T, Meletiadis J, Roilides E, Kleiner DE, Schaufele R, Roden M, Harrington S, Dad L, Segal B, Walsh TJ (2007) Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis. Am J Clin Pathol 127: 349–355

    Article  PubMed  Google Scholar 

  59. Torres HA, Rivero GA, Lewis RE, Hachem R, Raad II, Kontoyiannis DP (2003) Aspergillosis caused by non-fumigatus Aspergillus species: risk factors and in vitro susceptibility compared with Aspergillus fumigatus. Diagn Microbiol Infect Dis 46:25–28

    Article  PubMed  Google Scholar 

  60. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP (2008) Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc 83:181–194

    Article  PubMed  CAS  Google Scholar 

  61. Vagefi PA, Cosimi AB, Ginns LC, Kotton CN (2008) Cutaneous Aspergillus ustus in a lung transplant recipient: emergence of a new opportunistic fungal pathogen. J Heart Lung Transplant 27:131–134

    Article  PubMed  Google Scholar 

  62. Van Den NE, Michaux L, Layios N, Costantini S, Francart J, Lambert C, Sonet A, Andre M, Robert A, Ferrant A (2004) High incidence of complications after 2-chloro-2’-deoxyadenosine combined with cyclophosphamide in patients with advanced lymphoproliferative malignancies. Ann Hematol 83:356–363

    Article  Google Scholar 

  63. Varkey JB, Perfect JR (2008) Rare and emerging fungal pulmonary infections. Semin Respir Crit Care Med 29:121–131

    Article  PubMed  Google Scholar 

  64. Vera A, Hubscher SG, McMaster P, Buckels JA (2002) Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report. Transplantation 73:145–147

    Article  PubMed  Google Scholar 

  65. Virgili A, Zampino MR, Mantovani L (2002) Fungal skin infections in organ transplant recipients. Am J Clin Dermatol 3:19–35

    Article  PubMed  Google Scholar 

  66. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E (2004) Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 10(Suppl 1):48–66

    Article  PubMed  Google Scholar 

  67. Walsh TJ, Lutsar I, Driscoll T, Dupont B, Roden M, Ghahramani P, Hodges M, Groll AH, Perfect JR (2002) Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J 21:240–248

    Article  PubMed  Google Scholar 

  68. Wingard JR (1999) Opportunistic infections after blood and marrow transplantation. Transpl Infect Dis 1:3–20

    Article  PubMed  CAS  Google Scholar 

  69. Wingard JR (2007) New approaches to invasive fungal infections in acute leukemia and hematopoietic stem cell transplant patients. Best Pract Res Clin Haematol 20: 99–107

    Article  PubMed  Google Scholar 

  70. Yuen KY, Woo PC, Ip MS, Liang RH, Chiu EK, Siau H, Ho PL, Chen FF, Chan TK (1997) Stage-specific manifestation of mold infections in bone marrow transplant recipients: risk factors and clinical significance of positive concentrated smears. Clin Infect Dis 25:37–42

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Hematology Unit and Mycology Laboratory, University Hospital, Universidade Federal do Rio de Janeiro. Rua Professor Rodolpho Paulo Rocco, 255 Sala 4A, 12 21941-913, Rio de Janeiro, Brazil

    Marcia Garnica & Marcio Nucci

Authors
  1. Marcia Garnica
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcio Nucci
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcio Nucci .

Editor information

Editors and Affiliations

  1. Service de Réanimation Médicale, Hôpital Saint Louis, Avenue Claude Vellefaux 1, Paris, 75010, France

    Elie Azoulay

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Garnica, M., Nucci, M. (2011). Emerging Fungal Infections. In: Azoulay, E. (eds) Pulmonary Involvement in Patients with Hematological Malignancies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15742-4_27

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-15742-4_27

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-15741-7

  • Online ISBN: 978-3-642-15742-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation