Fungal Infections

  • Ana Paula VelezEmail author
  • Jorge Lamarche
  • John N. Greene


The incidence of fungal infection in neutropenic patients is increasing as a result of new advances of chemotherapy, stem cell transplantation with associated immunosuppressive therapies, use of broad spectrum antibiotics, and central venous devices. As this susceptible population is living longer, even uncommon and more resistant fungal organisms can develop despite prophylactic antifungals.

This chapter will focus on common fungal infections seen in neutropenic patients, particularly yeast and molds. Endemic mycoses are not common in this population and will not be discussed in this chapter.


Candida Species Non Candida yeast infections Molds Aspergillus Fusarium Scedosporium Zygomecetes Mucor Dermatiaceous fungi Hyalohyphomycosis Mucorales 


  1. 1.
    Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–50.PubMedGoogle Scholar
  2. 2.
    Arendrup MC. Candida and candidaemia. Susceptibility and epidemiology. Dan Med J. 2013;60(11):B4698.PubMedGoogle Scholar
  3. 3.
    Jung DS, Farmakiotis D, Jiang Y, Tarrand JJ, Kontoyiannis DP. Uncommon Candida species Fungemia among cancer patients, Houston, Texas, USA. Emerg Infect Dis. 2015;21(11):1942–50.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Tsay S, Kallen A, Jackson BR, Chiller TM, Vallabhaneni S. Approach to the investigation and management of patients with Candida auris, an emerging multidrug-resistant yeast. Clin Infect Dis. 2018;66(2):306–11.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Saris K, Meis JF, Voss A. Candida auris. Curr Opin Infect Dis. 2018;31(4):34–340.Google Scholar
  6. 6.
    Dovnik A, Golle A, Novak D, Arko D, Takac I. Treatment of vulvovaginal candidiasis: a review of the literature. Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 2015;24(1):5–7.PubMedGoogle Scholar
  7. 7.
    Metin A, Dilek N, Bilgili SG. Recurrent candidal intertrigo: challenges and solutions. Clin Cosmet Investig Dermatol. 2018;11:175–85.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Prodhan T, Yacoub AT, Jones L, Mai J, Greene J. Non-candida yeasts fungemia in cancer patients: a retrospective analysis at a referral cancer center, 1999–2014. Infect Dis Clin Pract. 2015;23(5):260–2.Google Scholar
  9. 9.
    Hazen KC. New and emerging yeast pathogens. Clin Microbiol Rev. 1995;8(4):462–78.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Marcon MJ, Powell DA. Epidemiology, diagnosis, and management of Malassezia furfur systemic infection. Diagn Microbiol Infect Dis. 1987;7(3):161–75.PubMedGoogle Scholar
  11. 11.
    Marcon MJ, Powell DA. Human infections due to Malassezia spp. Clin Microbiol Rev. 1992;5(2):101–19.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Iatta R, Cafarchia C, Cuna T, Montagna O, Laforgia N, Gentile O, et al. Bloodstream infections by Malassezia and Candida species in critical care patients. Med Mycol. 2014;52(3):264–9.PubMedGoogle Scholar
  13. 13.
    Martino P, Venditti M, Micozzi A, Morace G, Polonelli L, Mantovani MP, et al. Blastoschizomyces capitatus: an emerging cause of invasive fungal disease in leukemia patients. Rev Infect Dis. 1990;12(4):570–82.PubMedGoogle Scholar
  14. 14.
    Tsiodras S, Papageorgiou S, Meletiadis J, Tofas P, Pappa V, Panayiotides J, et al. Rhodotorula mucilaginosa associacted meningitis: a subacute entity with high mortality. Case report and review. Med Mycol Case Rep. 2014;6:46–50.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Tashiro T, Nagai H, Nagaoka H, Goto Y, Kamberi P, Nasu M. Trichosporon beigelii pneumonia in patients with hematologic malignancies. Chest. 1995;108(1):190–5.PubMedGoogle Scholar
  16. 16.
    Ebright JR, Fairfax MR, Vazquez JA. Trichosporon asahii, a non-candida yeast that caused fatal septic shock in a patient without cancer or neutropenia. Clin Infect Dis. 2001;33(5):E28–30.PubMedGoogle Scholar
  17. 17.
    Surmont I, Vergauwen B, Marcelis L, Verbist L, Verhoef G, Boogaerts M. First report of chronic meningitis caused by Trichosporon beigelii. European journal of clinical microbiology & infectious diseases : official publication of the. Eur Soc Clin Microbiol. 1990;9(3):226–9.Google Scholar
  18. 18.
    Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, Rodriguez JR, Chen E, Rex JH. In vitro antifungal susceptibilities of Trichosporon species. Antimicrob Agents Chemother. 2002;46(4):1144–6.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Serena C, Pastor FJ, Gilgado F, Mayayo E, Guarro J. Efficacy of micafungin in combination with other drugs in a murine model of disseminated trichosporonosis. Antimicrob Agents Chemother. 2005;49(2):497–502.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Diekema DJ, Petroelje B, Messer SA, Hollis RJ, Pfaller MA. Activities of available and investigational antifungal agents against rhodotorula species. J Clin Microbiol. 2005;43(1):476–8.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Koc AN, Copur Cicek A, Kaynar L, Sav H, Kasap Tekinsen FF, Atalay MA. Three cases of fungemia caused by Blastoschizomyces capitatus. Mikrobiyoloji bulteni. 2013;47(4):734–41.PubMedGoogle Scholar
  22. 22.
    Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol. 1998;36(10):2950–6.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis. 2005;41(11):1559–68.PubMedGoogle Scholar
  24. 24.
    Popiel KY, Wong P, Lee MJ, Langelier M, Sheppard DC, Vinh DC. Invasive Saccharomyces cerevisiae in a liver transplant patient: case report and review of infection in transplant recipients. Transpl Infect Dis: Off J Transpl Soc. 2015;17(3):435–41.Google Scholar
  25. 25.
    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(7):909–17.PubMedGoogle Scholar
  26. 26.
    Abers MS, Ghebremichael MS, Timmons AK, Warren HS, Poznansky MC, Vyas JM. A critical reappraisal of prolonged neutropenia as a risk factor for invasive pulmonary aspergillosis. Open Forum Infect Dis. 2016;3(1):ofw036.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Segal BH. Aspergillosis. N Engl J Med. 2009;360(18):1870–84.PubMedGoogle Scholar
  28. 28.
    Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Executive summary: practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;63(4):433–42.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Peman J, Salavert M. Invasive fungal disease due to Scedosporium, Fusarium and mucorales. Revista iberoamericana de micologia. 2014;31(4):242–8.PubMedGoogle Scholar
  30. 30.
    Walsh TJ, Gamaletsou MN. Treatment of fungal disease in the setting of neutropenia. Hematology Am Soc Hematol Educ Program. 2013;2013:423–7.PubMedGoogle Scholar
  31. 31.
    Lamoth F, Chung SJ, Damonti L, Alexander BD. Changing epidemiology of invasive mold infections in patients receiving azole prophylaxis. Clin Infect Dis. 2017;64(11):1619–21.PubMedGoogle Scholar
  32. 32.
    Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev. 1994;7(4):479–504.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Tortorano AM, Richardson M, Roilides E, van Diepeningen A, Caira M, Munoz P, et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clinical microbiology and infection : the official publication of the European Society of Clinical. Microbiol Infect Dis. 2014;20(Suppl 3):27–46.Google Scholar
  34. 34.
    Hayden RT, Isotalo PA, Parrett T, Wolk DM, Qian X, Roberts GD, et al. In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Molecul Pathol: Am J Surg Pathol, Part B. 2003;12(1):21–6.Google Scholar
  35. 35.
    Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management. Blood. 1997;90(3):999–1008.PubMedGoogle Scholar
  36. 36.
    Velez A, Greene J, L. Vincent A, M. Elko-Simms Impact and etiology of periungual toe infections in neutropenic patients. Infectious Diseases in Clinical Practice. 2012;20(6):e31–e34.Google Scholar
  37. 37.
    Liu K, Howell DN, Perfect JR, Schell WA. Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology. Am J Clin Pathol. 1998;109(1):45–54.PubMedGoogle Scholar
  38. 38.
    Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007;20(4):695–704.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Nucci F, Nouer SA, Capone D, Anaissie E, Nucci M. Fusariosis. Semin Respir Crit Care Med. 2015;36(5):706–14.PubMedGoogle Scholar
  40. 40.
    Hue FX, Huerre M, Rouffault MA, de Bievre C. Specific detection of fusarium species in blood and tissues by a PCR technique. J Clin Microbiol. 1999;37(8):2434–8.PubMedPubMedCentralGoogle Scholar
  41. 41.
    McCarthy MW, Katragkou A, Iosifidis E, Roilides E, Walsh TJ. Recent advances in the treatment of scedosporiosis and fusariosis. J Fungi (Basel, Switzerland). 2018;4(2):1–16.PubMedCentralGoogle Scholar
  42. 42.
    Tupaki-Sreepurna A, Kindo AJ. Fusarium: the versatile pathogen. Indian J Med Microbiol. 2018;36(1):8–17.PubMedGoogle Scholar
  43. 43.
    Taj-Aldeen SJ. Reduced multidrug susceptibility profile is a common feature of opportunistic fusarium species: fusarium multi-drug resistant pattern. J Fungi (Basel, Switzerland). 2017;3(2):1–15.PubMedCentralGoogle Scholar
  44. 44.
    Al-Hatmi AMS, Bonifaz A, Ranque S, Sybren de Hoog G, Verweij PE, Meis JF. Current antifungal treatment of fusariosis. Int J Antimicrob Agents. 2018;51(3):326–32.PubMedGoogle Scholar
  45. 45.
    Cordoba S, Rodero L, Vivot W, Abrantes R, Davel G, Vitale RG. In vitro interactions of antifungal agents against clinical isolates of Fusarium spp. Int J Antimicrob Agents. 2008;31(2):171–4.PubMedGoogle Scholar
  46. 46.
    Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, et al. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis. 2006;42(10):1398–403.PubMedGoogle Scholar
  47. 47.
    Nucci M, Anaissie E. Emerging fungi. Infect Dis Clin N Am. 2006;20(3):563–79.Google Scholar
  48. 48.
    Gilgado F, Cano J, Gene J, Guarro J. Molecular phylogeny of the Pseudallescheria boydii species complex: proposal of two new species. J Clin Microbiol. 2005;43(10):4930–42.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008;21(1):157–97.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Ramirez-Garcia A, Pellon A, Rementeria A, Buldain I, Barreto-Bergter E, Rollin-Pinheiro R, et al. Scedosporium and Lomentospora: an updated overview of underrated opportunists. Med Mycol. 2018;56(suppl_1):102–25.PubMedGoogle Scholar
  51. 51.
    Husain S, Munoz P, Forrest G, Alexander BD, Somani J, Brennan K, et al. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis. 2005;40(1):89–99.PubMedGoogle Scholar
  52. 52.
    Berenguer J, Rodriguez-Tudela JL, Richard C, Alvarez M, Sanz MA, Gaztelurrutia L, et al. Deep infections caused by Scedosporium prolificans. A report on 16 cases in Spain and a review of the literature. Scedosporium Prolificans Spanish Study Group Medicine. 1997;76(4):256–65.Google Scholar
  53. 53.
    Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Heath CH, Lutsar I, et al. Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients. Antimicrob Agents Chemother. 2008;52(5):1743–50.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Gilgado F, Serena C, Cano J, Gene J, Guarro J. Antifungal susceptibilities of the species of the Pseudallescheria boydii complex. Antimicrob Agents Chemother. 2006;50(12):4211–3.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013;98(4):492–504.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Mantadakis E, Samonis G. Clinical presentation of zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):15–20.PubMedGoogle Scholar
  57. 57.
    Downie ML, Alghounaim M, Davidge KM, Yau Y, Walsh TJ, Pope E, et al. Isolated cutaneous mucormycosis in a pediatric renal transplant recipient. Pediatr Transplant. 2018;22(4):e13172.PubMedGoogle Scholar
  58. 58.
    Nayagam LS, Vijayanand B, Balasubramanian S. Isolated renal mucormycosis in an immunocompetent child. Indian J Nephrol. 2014;24(5):321–3.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53.PubMedGoogle Scholar
  60. 60.
    Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV. Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000;30(6):851–6.PubMedGoogle Scholar
  61. 61.
    Kauffman CA, Malani AN. Zygomycosis: an emerging fungal infection with new options for management. Curr Infect Dis Rep. 2007;9(6):435–40.PubMedGoogle Scholar
  62. 62.
    Trifilio SM, Bennett CL, Yarnold PR, McKoy JM, Parada J, Mehta J, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 2007;39(7):425–9.PubMedGoogle Scholar
  63. 63.
    Lanternier F, Dannaoui E, Morizot G, Elie C, Garcia-Hermoso D, Huerre M, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005-2007). Clin Infect Dis. 2012;54(Suppl 1):S35–43.PubMedGoogle Scholar
  64. 64.
    Harril WC, Stewart MG, Lee AG, Cernoch P. Chronic rhinocerebral mucormycosis. Laryngoscope. 1996;106(10):1292–7.PubMedGoogle Scholar
  65. 65.
    Castrejon-Perez AD, Welsh EC, Miranda I, Ocampo-Candiani J, Welsh O. Cutaneous mucormycosis. An Bras Dermatol. 2017;92(3):304–11.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, 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(3):433–44.PubMedPubMedCentralGoogle Scholar
  67. 67.
    van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42(7):e61–5.PubMedGoogle Scholar
  68. 68.
    Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR 3rd, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–37.PubMedGoogle Scholar
  69. 69.
    Abidi MZ, Sohail MR, Cummins N, Wilhelm M, Wengenack N, Brumble L, et al. Stability in the cumulative incidence, severity and mortality of 101 cases of invasive mucormycosis in high-risk patients from 1995 to 2011: a comparison of eras immediately before and after the availability of voriconazole and echinocandin-amphotericin combination therapies. Mycoses. 2014;57(11):687–98.PubMedPubMedCentralGoogle Scholar
  70. 70.
    Kyvernitakis A, Torres HA, Jiang Y, Chamilos G, Lewis RE, Kontoyiannis DP. Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis. Clin Microbiol Infect: Off Publ Eur Soc Clin Microbiol Infect Dis. 2016;22(9):811.e1–8.Google Scholar
  71. 71.
    Schieffelin JS, Garcia-Diaz JB, Loss GE Jr, Beckman EN, Keller RA, Staffeld-Coit C, et al. Phaeohyphomycosis fungal infections in solid organ transplant recipients: clinical presentation, pathology, and treatment. Transpl Infect Dis: Off J Transplant Soc. 2014;16(2):270–8.Google Scholar
  72. 72.
    McCarty TP, Baddley JW, Walsh TJ, Alexander BD, Kontoyiannis DP, Perl TM, et al. Phaeohyphomycosis in transplant recipients: results from the transplant associated infection surveillance network (TRANSNET). Med Mycol. 2015;53(5):440–6.PubMedGoogle Scholar
  73. 73.
    Revankar SG, Patterson JE, Sutton DA, Pullen R, Rinaldi MG. Disseminated phaeohyphomycosis: review of an emerging mycosis. Clin Infect Dis. 2002;34(4):467–76.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ana Paula Velez
    • 1
    Email author
  • Jorge Lamarche
    • 2
  • John N. Greene
    • 3
  1. 1.University of South FloridaTampaUSA
  2. 2.USF Morsani College of Medicine James Haley VA HospitalJames Haley VA HospitalTampaUSA
  3. 3.USF Morsani College of MedicineMoffitt Cancer Center and Research InstituteTampaUSA

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