Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment

  • 1372 Accesses

  • 77 Citations


In recent years the number of opportunistic invasive fusariosis has increased significantly, the main factors involved in these infections being reviewed here. In spite of the extensive literature published the advances in the management of disseminated fusariosis have been very poor and it remains a severe infection, refractory to treatment and with a high mortality rate. There are no ideal therapies and the presence of neutropenia has a critical part to play in the outcome of the infection. At least 70 species have been involved in fusariosis. Fusarium solani species complex is responsible for nearly 60 % of the cases and F. oxysporum species complex for approximately 20 % of them. Most of the infections are caused by four species, i.e. F. petroliphilum, F. keratoplasticum and other two unnamed phylogenetic species. The efficacy of amphotericin B and voriconazole, the most used antifungal drugs, for treating invasive fusariosis are controversial but in general the percentage of patients cured in the different clinical trials is low. Infections by Fusarium verticillioides seem to have the best prognosis. The recent release of complete genome sequences of the most clinically relevant species and the emergence of fungal genomics offer excellent opportunities for examining the multifactorial processes of Fusarium pathogenicity. Using knockout mutants of genes encoding sequence-specific proteins, several virulence factors have been characterized.

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


  1. 1.

    Anaissie E, Kantarjian H, Jones P, Barlogie B, Luna M, Lopez-Berestein G et al (1986) Fusarium. A newly recognized fungal pathogen in immunosuppressed patients. Cancer 57(11):2141–2145

  2. 2.

    Guarro J, Gené J (1995) Opportunistic fusarial infections in humans. Eur J Clin Microbiol Infect Dis 14(9):741–754

  3. 3.

    Nucci M, Anaissie E, Queiroz-Telles F, Martins CA, Trabasso P, Solza C et al (2003) Outcome predictor of 84 patients with hematologic malignancies and Fusarium infection. Cancer 98(2):315–319. doi:10.1002/cncr.11510

  4. 4.

    Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S et al (2004) Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis 38(9):1237–1242. doi:10.1086/383319

  5. 5.

    Nucci M, Anaissie E (2007) Fusarium infections in immunocompromised patients. Clin Microbiol Rev 20(4):695–704. doi:10.1128/CMR.00014-07

  6. 6.

    Sutton DA, Brandt MB (2011) Fusarium and other opportunistic hyaline fungi, p. 1853–1879. In: Versalovic J, Carroll K, Funke G, Jorgensen JH, Landry ML (eds) Manual of clinical microbiology, 10th edn. ASM Press, Washington, DC, pp 1853–1879

  7. 7.

    Short DPG, O’Donnell K, Zhang N, Juba JH, Geiser DM (2011) Widespread occurrence of diverse human pathogenc types of the fungus Fusarium detected in plumbing drains. J Clin Microbiol 49(12):4264–4272. doi:10.1128/JCM.05468-11

  8. 8.

    Raad I, Tarrand J, Hanna H, Albitar M, Janssen E, Boktour M et al (2002) Epidemiology, molecular mycology, and environmental sources of Fusarium infection in patients with cancer. Infect Control Hosp Epidemiol 23(9):532–537

  9. 9.

    Mayayo E, Pujol I, Guarro J (1999) Experimental pathogenicity of four opportunist Fusarium species. J Med Microbiol 48:363–366

  10. 10.

    Coleman JJ, Rounsley SD, Rodriguez-Carres M, Kuo A, Wasmann CC, Grimwood J et al (2009) The genome of Nectria haematococca: contribution of supernumerary chromosomes to gene expansion. PLoS Genet 5(8):e1000618. doi:10.1371/journal.pgen.1000618.s01811

  11. 11.

    Ma LJ, van der Does HC, Borkovich KA, Coleman JJ, Daboussi MJ, Di Pietro A et al (2010) Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium. Nature 464(7287):367–373. doi:10.1038/nature08850

  12. 12.

    Ortoneda M, Guarro J, Madrid MP, Caracuel Z, Roncero MI, Mayayo E et al (2004) Fusarium oxysporum as a multihost model for the genetic dissection of fungal virulence in plants and mammals. Infect Immun 72(3):1760–1766. doi:10.1128/IAI.72.3.1760-1766.2004

  13. 13.

    Ruiz-Roldán MC, Garre V, Guarro J, Roncero MIG (2008) Role of the white collar 1 photoreceptor in carotenogenesis, UV resistance, hydrophobicity, and virulence of Fusarium oxysporum. Eukaryot Cell 7(7):1227–1230. doi:10.1128/EC.00072-08

  14. 14.

    Prados-Rosales RC, Serena C, Delgado-Jarana J, Guarro J, Di Pietro A (2006) Distinct signalling pathways coordinately contribute to virulence of Fusarium oxysporum on mammalian hosts. Microb Infect 8(14–15):2825–2831. doi:10.1016/j.micinf.2006.08.015

  15. 15.

    Hua X, Yuan X, Di Pietro A, Wilhelmus KR (2010) The molecular pathogenicity of Fusarium keratitis: a fungal transcriptional regulator promotes hyphal penetration in cornea. Cornea 29(12):1440–1444. doi:10.1097/ICO.0b013e3181d8383a

  16. 16.

    Prados-Rosales RC, Roldán-Rodriguez R, Serena C, López-Berges MS, Guarro J, Martínez-del-Pozo A et al (2012) A PR-1-like protein of Fusarium oxysporum functions in virulence on mammalian hosts. J Biol Chem 287(26):21970–21979. doi:10.1074/jbc.M112.364034

  17. 17.

    López-Berges MS, Hera C, Sulyok M, Schäfer K, Capilla J, Guarro et al (2013) The velvet complex governs mycotoxin production and virulence of Fusarium oxysporum on plant and mammalian hosts. Mol Microbiol 87(1):49–65. doi:10.1111/mmi.12082

  18. 18.

    López-Berges MS, Capilla J, Turrà D, Schafferer L, Matthijs S, Jöchl C et al (2012) HapX-mediated iron homeostasis is essential for rhizosphere competence and virulence of the soilborne pathogen Fusarium oxysporum. Plant Cell 24(9):3805–3822. doi:10.1105/tpc.112.098624

  19. 19.

    O’Donnell K, Sutton DA, Rinaldi MG, Sarver BA, Balajee SA, Schroers HJ et al (2010) Internet-accessible DNA sequence database for identifying fusaria from human and animal infections. J Clin Microbiol 48(10):3708–3718. doi:10.1128/JCM.00989-10

  20. 20.

    Hawksworth DL (2011) A new dawn for the naming of fungi: impacts of decisions made in Melbourne in July 2011 on the future publication and regulation of fungal names. IMA Fungus 2(2):155–162. doi:10.5598/imafungus.2011.02.02.06

  21. 21.

    Geiser DM, Aoki T, Bacon CW, Baker SE, Bhattacharyya MK, Brandt ME et al (2013) One Fungus, One Name: defining the genus Fusarium in a scientifically robust way that preserves longstanding use. Phytopathology 103(5):400–408. doi:10.1094/PHYTO-07-12-0150-LE

  22. 22.

    Guarro J, Gené J (1992) Fusarium infections. Criteria for the identification of the responsible species. Mycoses 35(5–6):109–114

  23. 23.

    Gerlach W, Nirenberg H (1982) The genus Fusarium—A pictorial atlas. Mitteilungen aus der Biologischen Bundesanstalt Für Land-und Forstwirtschaft Berlin-Dahlem 209:1–405

  24. 24.

    Booth C (1971) The genus Fusarium. Commonwealth Mycological Institute, Kew, Surrey, United Kingdom

  25. 25.

    Leslie JF, Summerell BA (2006) The Fusarium laboratory manual. Blackwell Publishing, Iowa, USA

  26. 26.

    Short DPG, O’Donnell K, Thrane U, Nielsen KF, Zhang N, Juba JH et al (2013) Phylogenetic relationships among members of the Fusarium solani species complex in human infections and the descriptions of F. keratoplasticum sp. nov. and F. petroliphilum stat. nov. Fungal Genet Biol 53:59–70. doi:10.1016/j.fgb.2013.01.004

  27. 27.

    Balajee SA, Borman AM, Brandt ME, Cano J, Cuenca-Estrella M, Dannaoui E et al (2009) Sequence-based identification of Aspergillus, Fusarium and Mucorales species in the clinical mycology laboratory: where are we and where should we go from here? J Clin Microbiol 47(4):877–884. doi:10.1128/JCM.01685-08

  28. 28.

    Boutati EI, Annaissie EJ (1997) Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years’ experience at a cancer center and implications for management. Blood 90(3):999–1008

  29. 29.

    Campo M, Lewis RE, Kontoyiannis DP (2010) Invasive fusariosis in patients with hematologic malignancies at a cancer center: 1998–2009. J Infect 60(5):331–337. doi:10.1016/j.jinf.2010.01.010

  30. 30.

    Guarro J, Nucci M, Akiti T et al (2000) Mixed infection caused by two species of Fusarium in a human immunodeficiency virus-positive patient. J Clin Microbiol 38(9):3460–3462

  31. 31.

    Migheli Q, Balmas V, Harak H, Sanna S, Scherm B, Aoki T et al (2010) Molecular phylogenetic diversity of dermatologic and other human pathogenic fusarial isolates from hospitals in northern and central Italy. J Clin Microbiol 48(4):1076–1084. doi:10.1128/JCM.01765-09

  32. 32.

    Marom EM, Holmes AM, Bruzzi JF, Truong MT, O’Sullivan PJ, Kontoyiannis DP (2008) Imaging of pulmonary fusariosis in patients with hematologic malignancies. AJR Am J Roentgenol 190(6):1605–1609. doi:10.2214/AJR.07.3278

  33. 33.

    Muhammed M, Coleman JJ, Carneiro HA, Mylonakis E (2011) The challenge of managing fusariosis. Virulence 2(2):91–96. doi:10.4161/viru.2.2.15015

  34. 34.

    Marinach-Patrice C, Lethuillier A, Marly A, Brossas JY, Gené J, Symoens F et al (2009) Use of mass spectrometry to identify clinical Fusarium isolates. Clin Microbiol Infect 15(7):634–642. doi:10.1111/j.1469-0691.2009.02758.x

  35. 35.

    Mikulska M, Furfaro E, Del Bono V, Gualandi F, Raiola AM, Molinari MP et al (2012) Galactomannan testing might be useful for early diagnosis of fusariosis. Diagn Microbiol Infect Dis 72(4):367–369. doi:10.1016/j.diagmicrobio.2011.12.009

  36. 36.

    Tortorano AM, Esposto MC, Prigitano A, Grancini A, Ossi C, Cavanna C et al (2012) Cross-reactivity of Fusarium spp. In the Aspergillus galactomannan enzyme-linked immunosorbent assay. J Clin Microbiol 50(3):1051–1053. doi:10.1128/JCM.05946-11

  37. 37.

    Bernal-Martínez L, Buitrago MJ, Castelli MV, Rodríguez-Tudela JL, Cuenca-Estrella M (2012) Detection of invasive infection caused by Fusarium solani and non-Fusarium solani species using a duplex quantitative PCR-based assay in a murine model of fusariosis. Med Mycol 50(3):270–275. doi:10.3109/13693786.2011.604047

  38. 38.

    Azor M, Gené J, Cano J, Guarro J (2007) Universal in vitro antifungal resistance of genetic clades of the Fusarium solani species complex. Antimicrob Agents Chemother 51(4):1500–1503. doi:10.1128/AAC.01618-06

  39. 39.

    Azor M, Gené J, Cano J, Sutton DA, Fothergill AW, Rinaldi MG et al (2008) In vitro antifungal susceptibility and molecular characterization of clinical isolates of Fusarium verticillioides (F. moniliforme) and Fusarium thapsinum. Antimicrob Agents Chemother 52(6):2228–2231. doi:10.1128/AAC.00176-08

  40. 40.

    Azor M, Cano J, Gené J, Guarro J (2009) High genetic diversity and poor in vitro response to antifungals of clinical strains of F. oxysporum. J Antimicrob Chemother 63(6):1152–1155. doi:10.1093/jac/dkp095

  41. 41.

    Azor M, Gené J, Cano J, Manikandan P, Venkatapathy N, Guarro J (2009) Less-frequent Fusarium species of clinical interest: correlation between mosphological and molecular identification and antifungal susceptibility. J Clin Microbiol 47(5):1463–1468. doi:10.1128/JCM.02467-08

  42. 42.

    Tortorano AM, Prigitano A, Dho G, Esposto MC, Gianni C, Grancini A et al (2008) Species distribution and in vitro antifungl susceptibility patterns of 75 clinical isolates of Fusarium spp. from Northern Italy. Antimicrob Agents Chemother 52(7):2683–2685. doi:10.1128/AAC.00272-08

  43. 43.

    Alastruey-Izquierdo A, Cuenca-Estrella M, Monzón A, Mellado E, Rodríguez-Tudela JL (2008) Antifungal susceptibility profile of clinical Fusarium spp. Isolates identified by molecular methods. J Antimicrob Chemother 61(4):805–809. doi:10.1093/jac/dkn022

  44. 44.

    Ortoneda M, Capilla J, Pastor FJ, Pujol I, Guarro J (2004) In vitro interactions of licensed and novel antifungal drugs against Fusarium spp. Diagn Microbiol Infect Dis 48(1):69–71

  45. 45.

    Córdoba S, Rodero L, Vivot W, Abrantes R, Davel G, Vitale RG (2008) In vitro interactions of antifungal agents against clinical isolates of Fusarium spp. Int J Antimicrob Agents 31(2):171–174

  46. 46.

    Spader TB, Venturini TP, Rossato L, Denardi LB, Cavalheiro PB, Botton SA et al (2013) Synergisms of voriconazole or itraconazole combined with other antifungal agents against Fusarium spp. Rev Iberoam Micol. doi:10.1016/j.riam.2013.01.002

  47. 47.

    Shalit I, Shadkchan Y, Mircus G, Osherov N (2009) In vitro synergy of caspofungin with licensed and novel antifungal drugs against clinical isolates of Fusarium spp. Med Mycol 47(5):457–462. doi:10.1080/13693780802232910

  48. 48.

    Guarro J (2011) Lessons from animal studies for the treatment of invasive human infections due to uncommon fungi. J Antimicrob Chemother 66(7):1447–1466. doi:10.1093/jac/dkr143

  49. 49.

    Odds FC, van Gerven F, Espinel-Ingroff A, Bartlett MS, Ghannoum MA, Lancaster MV et al (1998) Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 42(2):282–288

  50. 50.

    Perfect JR (2005) Treatment of non-Aspergillus moulds in immunocompromised patients, with amphotericin B lipid complex. Clin Infect Dis 40(suppl 6):S401–S408. doi:10.1086/429331

  51. 51.

    Walsh TJ, Hiemenz JW, Seibel NL, Perfect JR, Horwith G, Lee L et al (1998) Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis 26:1383–1396

  52. 52.

    Ruíz-Cendoya M, Mariné M, Guarro J (2008) Combined therapy in treatment of murine infection by Fusarium solani. J Antimicrob Chenother 62(3):543–546. doi:10.1093/jac/dkn215

  53. 53.

    Ruíz-Cendoya M, Mariné M, Rodriguez MM, Guarro J (2009) Interactions between triazoles and amphotericin B in treatment of disseminated murine infection by Fusarium oxysporum. Antimicrob Agents Chenother 53(4):1705–1708. doi:10.1128/AAC.01606-08

  54. 54.

    Ortoneda M, Capilla J, Pujol I, Guarro J (2002) Efficacy of liposomal amphotericin B in treatment of systemic murine fusariosis. Antimicrob Agents Chemother 46(7):2273–2275. doi:10.1128/AAC.46.7.2273-2275.2002

  55. 55.

    Guarro J, Pujol I, Mayayo E (1999) In vitro and in vivo experimental activities of antifungal agents against Fusarium solani. Antimicrob Agents Chemother 43(5):1256–1257

  56. 56.

    Spellberg B, Schwartz J, Fu Y, Avanesian V, Adler-Moore J, Edwards JE et al (2006) Comparison of antifungal treatments for murine fusariosis. J Antimicrob Chemother 58(5):973–979. doi:10.1093/jac/dkl378

  57. 57.

    Stanzani M, Tumietto F, Vianelli N, Baccarani M (2007) Update on the treatment of disseminated fusariosis: focus on voriconazole. Ther Clin Risk Manag 3(6):1165–1173

  58. 58.

    Perfect JR, Marr KA, Walsh TJ, Greenberg RN, DuPont B, de la Torre-Cisneros J et al (2003) Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 36(9):1122–1131

  59. 59.

    Lortholary O, Obenga G, Biswas P, Caillot D, Chachaty E, Bienvenu AL et al (2010) International retrospective analysis of 73 cases of invasive fusariosis treated with voriconazole. Antimicrob Agents Chemother 54(10):4446–4450. doi:10.1128/AAC.00286-10

  60. 60.

    Cudillo L, Girmenia C, Santilli S, Piccardi A, Dentamaro T, Tendas A et al (2005) Breakthrough fusariosis in a patient with acute lymphoblastic leukemia receiving voriconazole prophylaxis. Clin Infect Dis 40(8):1212–1213. doi:10.1086/428849

  61. 61.

    Kim MS, Lee HM, Sung HS, Won CH, Chang SE, Lee MW et al (2012) Breakthrough disseminated fusariosis in an immunocompromised patient on voriconazole therapy. Int J Dermatol 5(5):621–623. doi:10.1111/j.1365-4632.2010.04636.x

  62. 62.

    Raad I, Hachen RY, Herbrecht R, Graybill JR, Hare R, Corcoran G et al (2006) Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 42(10):1398–1403. doi:10.1086/503425

  63. 63.

    Lozano-Chiu M, Arikan S, Paetznick VL, Anaissie EJ, Loerenberg D, Rex JH (1999) Treatment of murine fusariosis with SCH 56592. Antimicrob Agents Chemother 43(3):589–591

  64. 64.

    Wiederhold NP, Najvar LK, Bocanegra R, Graybill JR, Patterson TF (2010) Efficacy of posaconazole as treatment and prophylaxis against Fusarium solani. Antimicrob Agents Chemother 54(3):1055–1059. doi:10.1128/AAC.01445-09

  65. 65.

    Ruíz-Cendoya M, Pastor J, Guarro J (2011) Combined therapy against murine-disseminated infection by Fusarium verticillioides. Mycopathologia 171(3):171–175. doi:10.1007/s11046-010-9364-8

  66. 66.

    Ruíz-Cendoya M, Pastor J, Capilla J, Guarro J (2011) Treatment of murine Fusarium verticillioides infection with liposomal amphotericin B plus terbinafine. Int J Antimicrob Agents 37(1):58–61. doi:10.1016/j.ijantimicag.2010.08.008

  67. 67.

    Makowsky MJ, Warkentin DI, Savoie ML (2005) Caspofungin and amphotericin B for disseminated Fusarium verticillioides in leukemia. Ann Pharmacother 39(7):1365–1366. doi:10.1345/aph.1D292

  68. 68.

    Cocchi S, Codeluppi M, Venturelli C, Bedini A, Grottola A, Gennari W et al (2011) Fusarium verticillioides fungemia in a liver transplantation patient. successful treatment with voriconazole. Diagn Microbiol Infect Dis 71(4):438–441. doi:10.1016/j.diagmicrobio.2011.08.024

  69. 69.

    Carneiro HA, Coleman JJ, Restrepo A (2011) Fusarium infection in lung transplant patients. Report of 6 cases and review of the literature. Medicine 90:69–80. doi:10.1097/MD.0b013e318207612d

  70. 70.

    Liu JY, Chen WT, Ko BS, Yao M, Hsueh PR, Hsiao CH et al (2011) Combination antifungal therapy for disseminated fusariosis in immunocompromised patients: a case report and literature review. Med Mycol 49(8):872–878. doi:10.3109/13693786.2011.567304

  71. 71.

    Lewis R, Hogan H, Howell A, Safdar A (2008) Progressive fusariosis: unpredictable posaconazole bioavailability, and feasibility of recombinant interferon-gamma plus granulocyte macrophage-colony stimulating factor for refractory disseminated infection. Leuk Lymphoma 49(1):163–165. doi:10.1080/10428190701724819

  72. 72.

    Arikan S, Lozano-Chiu M, Paetznick V, Rex JH (2002) In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother 46(1):245–247. doi:10.1128/AAC.46.1.245-247.2002

  73. 73.

    Vagace JM, Sanz-Rodríguez C, Casado MS, Alonso N, García-Domínguez M, García de la Llana F et al (2007) Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: a case report. BMC Infect Dis 7:40. doi:10.1186/1471-2334-7-40

  74. 74.

    Apostolidis J, Bouzani M, Platsuoka E, Belasiotou H, Stamouli M, Harhalakis N et al (2003) Resolution of fungemia due to Fusarium species in a patient with acute leukemia treated with caspofungin. Clin Infect Dis 36(10):1349–1350. doi:10.1086/374895

  75. 75.

    Labois A, Gray C, Lepretre S (2011) Successful treatment of disseminated fusariosis with voriconazole in an acute lymphoblastic leukaemia patient. Mycoses 54(suppl 4):8–11. doi:10.1111/j.1439-0507.2011.02136.x

  76. 76.

    Heyn K, Tredup A, Salvenmoser S, Müller FM (2005) Effect of voriconazole combined with micafungin against Candida, Aspergillus, and Scedosporium spp. and Fusarium solani. Antimicrob Agents Chemother 49(12):5157–5159. doi:10.1128/AAC.49.12.5157-5159.2005

Download references

Conflict of interest

The author declares no conflict of interest.

Author information

Correspondence to J. Guarro.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Guarro, J. Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment. Eur J Clin Microbiol Infect Dis 32, 1491–1500 (2013). https://doi.org/10.1007/s10096-013-1924-7

Download citation


  • Voriconazole
  • Aspergillosis
  • Caspofungin
  • Posaconazole
  • Terbinafine