Invasive Fungal Sinusitis in Immunocompromised Hosts

Chapter

Abstract

Invasive fungal sinusitis is an uncommon but life-threatening infection. Opportunistic molds, especially Aspergillus and Mucorales species, are the main causes of invasive fungal sinusitis. This entity primarily affects patients who are immunocompromised (e.g., hematologic malignancies, transplant recipients on immunosuppressive medications), or who have uncontrolled diabetes. The mortality is approximately 50% but varies widely (20–80%). For patients with malignancy as their risk factor, invasive fungal sinusitis can have profound effects on malignancy-related survival by delaying chemotherapy. Limited available interventions, suboptimal early diagnosis, and slow development of new anti-fungal agents have led to incremental improvements in outcomes. Early use of imaging, rapid institution of appropriate treatment, and a coordinated effort among specialists including infectious disease physicians and otolaryngologists are essential for improved survival. This chapter reviews the risk factors, clinical features, approach to diagnosis, and treatment of invasive fungal sinusitis.

Keywords

Invasive fungal sinusitis Rhinocerebral mucormycosis Invasive aspergillosis 

References

  1. 1.
    Davoudi S, Kumar VA, Jiang Y, Kupferman M, Kontoyiannis DP. Invasive mould sinusitis in patients with haematological malignancies: a 10 year single-centre study. J Antimicrob Chemother. 2015;70(10):2899–905.CrossRefGoogle Scholar
  2. 2.
    Chang C, Gershwin ME, Thompson GR. Fungal disease of the nose and sinuses: an updated overview. Curr Allergy Asthma Rep. 2013;13(2):152–61.CrossRefGoogle Scholar
  3. 3.
    Thompson GR, Patterson TF. Fungal disease of the nose and paranasal sinuses. J Allergy Clin Immunol. 2012;129(2):321–6.CrossRefGoogle Scholar
  4. 4.
    Humphrey JM, Walsh TJ, Gulick RM. Invasive Aspergillus sinusitis in human immunodeficiency virus infection: case report and review of the literature. Open Forum Infect Dis. 2016;3(3):ofw135.CrossRefGoogle Scholar
  5. 5.
    Turner JH, Soudry E, Nayak JV, Hwang PH. Survival outcomes in acute invasive fungal sinusitis: a systematic review and quantitative synthesis of published evidence. Laryngoscope. 2013;123(5):1112–8.CrossRefGoogle Scholar
  6. 6.
    Chen CY, Sheng WH, Cheng A, et al. Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan. BMC Infect Dis. 2011;11:250.CrossRefGoogle Scholar
  7. 7.
    Parikh SL, Venkatraman G, JM DG. Invasive fungal sinusitis: a 15-year review from a single institution. Am J Rhinol. 2004;18(2):75–81.PubMedGoogle Scholar
  8. 8.
    Even C, Bastuji-Garin S, Hicheri Y, et al. Impact of invasive fungal disease on the chemotherapy schedule and event-free survival in acute leukemia patients who survived fungal disease: a case-control study. Haematologica. 2011;96(2):337–41.CrossRefGoogle Scholar
  9. 9.
    Patterson TF. Aspergillus species. In: Bennett JE, Dolin R, Martin J, editors. Principles and practice of infectious diseases, vol. 2. 8th ed. Philadelphia, PA: Elsevier; 2015. p. 2895–908.Google Scholar
  10. 10.
    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.CrossRefGoogle Scholar
  11. 11.
    Dagenais TR, Keller NP. Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev. 2009;22(3):447–65.CrossRefGoogle Scholar
  12. 12.
    Michael RC, Michael JS, Ashbee RH, Mathews MS. Mycological profile of fungal sinusitis: an audit of specimens over a 7-year period in a tertiary care hospital in Tamil Nadu. Indian J Pathol Microbiol. 2008;51(4):493–6.CrossRefGoogle Scholar
  13. 13.
    Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005;191(8):1350–60.CrossRefGoogle Scholar
  14. 14.
    Jain R, Singhal SK, Singla N, Punia RS, Chander J. Mycological profile and antifungal susceptibility of fungal isolates from clinically suspected cases of fungal rhinosinusitis in a tertiary care hospital in North India. Mycopathologia. 2015;180(1-2):51–9.CrossRefGoogle Scholar
  15. 15.
    Fernandez IJ, Stanzani M, Tolomelli G, et al. Sinonasal risk factors for the development of invasive fungal sinusitis in hematological patients: are they important? Allergy Rhinol (Providence). 2011;2(1):6–11.CrossRefGoogle Scholar
  16. 16.
    Botterel F, Gross K, Ibrahim-Granet O, et al. Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro. BMC Microbiol. 2008;8:97.CrossRefGoogle Scholar
  17. 17.
    Zhao K, Dalton P. The way the wind blows: implications of modeling nasal airflow. Curr Allergy Asthma Rep. 2007;7(2):117–25.CrossRefGoogle Scholar
  18. 18.
    Brook I. The role of bacterial interference in otitis, sinusitis and tonsillitis. Otolaryngol Head Neck Surg. 2005;133(1):139–46.CrossRefGoogle Scholar
  19. 19.
    Azulay-Abulafia L, Sousa MA, Pussanti A, Coimbra DD, Vega H, Bernardes Filho F. Invasive aspergillosis in a user of inhaled cocaine: rhinosinusitis with bone and cartilage destruction. Rev Soc Bras Med Trop. 2014;47(4):533–6.CrossRefGoogle Scholar
  20. 20.
    Kaya S, Yavuz I, Cobanoğlu U, Ural A, Yılmaz G, Köksal I. Fatal sino-orbital aspergillosis in an immunocompetent case. Mikrobiyol Bul. 2011;45(3):546–52.PubMedGoogle Scholar
  21. 21.
    Pushker N, Meel R, Kashyap S, Bajaj MS, Sen S. Invasive aspergillosis of orbit in immunocompetent patients: treatment and outcome. Ophthalmology. 2011;118(9):1886–91.CrossRefGoogle Scholar
  22. 22.
    Kontoyiannis DP, Lewis RE. Agents of mucormycosis and entomophthoramycosis. In: Bennett JE, Dolin R, Blaser MJ, editors. Principles and practice of infectious diseases, vol. 2. 8th ed. Philadelphia, PA: Elsevier; 2014. p. 2909–19.Google Scholar
  23. 23.
    Liu M, Spellberg B, Phan QT, et al. The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice. J Clin Invest. 2010;120(6):1914–24.CrossRefGoogle Scholar
  24. 24.
    Gebremariam T, Lin L, Liu M, et al. Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis. J Clin Invest. 2016;126(6):2280–94.CrossRefGoogle Scholar
  25. 25.
    Howard DH. Acquisition, transport, and storage of iron by pathogenic fungi. Clin Microbiol Rev. 1999;12(3):394–404.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Artis WM, Fountain JA, Delcher HK, Jones HE. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes. 1982;31(12):1109–14.CrossRefGoogle Scholar
  27. 27.
    Piromchai P, Thanaviratananich S. Invasive fungal rhinosinusitis versus bacterial rhinosinusitis with orbital complications: a case-control study. ScientificWorldJournal. 2013;2013:453297.CrossRefGoogle Scholar
  28. 28.
    Iwen PC, Rupp ME, Hinrichs SH. Invasive mold sinusitis: 17 cases in immunocompromised patients and review of the literature. Clin Infect Dis. 1997;24(6):1178–84.CrossRefGoogle Scholar
  29. 29.
    Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53.CrossRefGoogle Scholar
  30. 30.
    del Giudice P, Moulonguet L, Ranchin B, Abraham B, Sellier P. Cutaneous aspergillus invasion from sinusitis. Clin Infect Dis. 1999;29(3):690–1.CrossRefGoogle Scholar
  31. 31.
    DelGaudio JM, Swain RE, Kingdom TT, Muller S, Hudgins PA. Computed tomographic findings in patients with invasive fungal sinusitis. Arch Otolaryngol Head Neck Surg. 2003;129(2):236–40.CrossRefGoogle Scholar
  32. 32.
    Kim JH, Kang BC, Lee JH, Jang YJ, Lee BJ, Chung YS. The prognostic value of gadolinium-enhanced magnetic resonance imaging in acute invasive fungal rhinosinusitis. J Infect. 2015;70(1):88–95.CrossRefGoogle Scholar
  33. 33.
    Monteagudo M, Palazón-García E, Lozano-Setién E, García-García J. The ‘black turbinate sign’ in a case of rhinocerebral mucormycosis. Rev Neurol. 2014;58(5):234–5.PubMedGoogle Scholar
  34. 34.
    Gillespie MB, O’Malley BW, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host. Arch Otolaryngol Head Neck Surg. 1998;124(5):520–6.CrossRefGoogle Scholar
  35. 35.
    Taxy JB, El-Zayaty S, Langerman A. Acute fungal sinusitis: natural history and the role of frozen section. Am J Clin Pathol. 2009;132(1):86–93.CrossRefGoogle Scholar
  36. 36.
    Zimmermann N, Hagen MC, Schrager JJ, Hebbeler-Clark RS, Masineni S. Utility of frozen section analysis for fungal organisms in soft tissue wound debridement margin determination. Diagn Pathol. 2015;10:188.CrossRefGoogle Scholar
  37. 37.
    Safdar A, Dommers MP, Talwani R, Thompson CR. Intracranial perineural extension of invasive mycosis: a novel mechanism of disease propagation by Aspergillus fumigatus. Clin Infect Dis. 2002;35(5):e50–3.CrossRefGoogle Scholar
  38. 38.
    Tarrand JJ, Lichterfeld M, Warraich I, et al. Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol. 2003;119(6):854–8.CrossRefGoogle Scholar
  39. 39.
    Obayashi T, Yoshida M, Mori T, et al. Plasma (1-->3)-beta-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet. 1995;345(8941):17–20.CrossRefGoogle Scholar
  40. 40.
    Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. β-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–70.CrossRefGoogle Scholar
  41. 41.
    Nakanishi W, Fujishiro Y, Nishimura S, Fukaya T. Clinical significance of (1-->3)-beta-d-glucan in a patient with invasive sino-orbital aspergillosis. Auris Nasus Larynx. 2009;36(2):224–7.CrossRefGoogle Scholar
  42. 42.
    Marr KA, Laverdiere M, Gugel A, Leisenring W. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis. 2005;40(12):1762–9.CrossRefGoogle Scholar
  43. 43.
    Choi SH, Kang ES, Eo H, et al. Aspergillus galactomannan antigen assay and invasive aspergillosis in pediatric cancer patients and hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2013;60(2):316–22.CrossRefGoogle Scholar
  44. 44.
    Kostamo K, Richardson M, Eerola E, et al. Negative impact of Aspergillus galactomannan and DNA detection in the diagnosis of fungal rhinosinusitis. J Med Microbiol. 2007;56(Pt 10):1322–7.CrossRefGoogle Scholar
  45. 45.
    Torelli R, Sanguinetti M, Moody A, et al. Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol. 2011;49(12):4273–8.CrossRefGoogle Scholar
  46. 46.
    Millon L, Herbrecht R, Grenouillet F, et al. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clin Microbiol Infect. 2016;22(9):810.e1–8.CrossRefGoogle Scholar
  47. 47.
    Salehi E, Hedayati MT, Zoll J, et al. Discrimination of aspergillosis, mucormycosis, fusariosis, and scedosporiosis in formalin-fixed paraffin-embedded tissue specimens by use of multiple real-time quantitative PCR assays. J Clin Microbiol. 2016;54(11):2798–803.CrossRefGoogle Scholar
  48. 48.
    Bialek R, Konrad F, Kern J, et al. PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue. J Clin Pathol. 2005;58(11):1180–4.CrossRefGoogle Scholar
  49. 49.
    Zuniga MG, Turner JH. Treatment outcomes in acute invasive fungal rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2014;22(3):242–8.CrossRefGoogle Scholar
  50. 50.
    Kasapoglu F, Coskun H, Ozmen OA, Akalin H, Ener B. Acute invasive fungal rhinosinusitis: evaluation of 26 patients treated with endonasal or open surgical procedures. Otolaryngol Head Neck Surg. 2010;143(5):614–20.CrossRefGoogle Scholar
  51. 51.
    Ferry AP, Abedi S. Diagnosis and management of rhino-orbitocerebral mucormycosis (phycomycosis). A report of 16 personally observed cases. Ophthalmology. 1983;90(9):1096–104.CrossRefGoogle Scholar
  52. 52.
    Kontoyiannis DP, Lewis RE. Treatment principles for the management of mold infections. Cold Spring Harb Perspect Med. 2014;5(4)CrossRefGoogle Scholar
  53. 53.
    Lanternier F, Poiree S, Elie C, et al. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J Antimicrob Chemother. 2015;70(11):3116–23.CrossRefGoogle Scholar
  54. 54.
    Dannaoui E, Meletiadis J, Mouton JW, Meis JF, Verweij PE, Network E. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother. 2003;51(1):45–52.CrossRefGoogle Scholar
  55. 55.
    Almyroudis NG, Sutton DA, Fothergill AW, Rinaldi MG, Kusne S. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother. 2007;51(7):2587–90.CrossRefGoogle Scholar
  56. 56.
    Nagappan V, Deresinski S. Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007;45(12):1610–7.CrossRefGoogle Scholar
  57. 57.
    Leventakos K, Lewis RE, Kontoyiannis DP. Fungal infections in leukemia patients: how do we prevent and treat them? Clin Infect Dis. 2010;50(3):405–15.CrossRefGoogle Scholar
  58. 58.
    Lewis RE, Lortholary O, Spellberg B, Roilides E, Kontoyiannis DP, Walsh TJ. How does antifungal pharmacology differ for mucormycosis versus aspergillosis? Clin Infect Dis. 2012;54(Suppl 1):S67–72.CrossRefGoogle Scholar
  59. 59.
    Ibrahim AS, Gebremariam T, Luo G, et al. Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes, and echinocandins. Antimicrob Agents Chemother. 2011;55(4):1768–70.CrossRefGoogle Scholar
  60. 60.
    Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47(3):364–71.CrossRefGoogle Scholar
  61. 61.
    Colon-Acevedo B, Kumar J, Richard MJ, Woodward JA. The role of adjunctive therapies in the management of invasive sino-orbital infection. Ophthal Plast Reconstr Surg. 2015;31(5):401–5.CrossRefGoogle Scholar
  62. 62.
    Mainville N, Jordan DR. Orbital apergillosis treated with retrobulbar amphotericin B. Orbit. 2012;31(1):15–7.CrossRefGoogle Scholar
  63. 63.
    Wakabayashi T, Oda H, Kinoshita N, Ogasawara A, Fujishiro Y, Kawanabe W. Retrobulbar amphotericin B injections for treatment of invasive sino-orbital aspergillosis. Jpn J Ophthalmol. 2007;51(4):309–11.CrossRefGoogle Scholar
  64. 64.
    Elefanti A, Mouton JW, Verweij PE, Zerva L, Meletiadis J. Susceptibility breakpoints for amphotericin B and Aspergillus species in an in vitro pharmacokinetic-pharmacodynamic model simulating free-drug concentrations in human serum. Antimicrob Agents Chemother. 2014;58(4):2356–62.CrossRefGoogle Scholar
  65. 65.
    Heo ST, Tatara AM, Jiménez-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.CrossRefGoogle Scholar
  66. 66.
    Carter KB, Loehrl TA, Poetker DM. Granulocyte transfusions in fulminant invasive fungal sinusitis. Am J Otolaryngol. 2012;33(6):663–6.CrossRefGoogle Scholar
  67. 67.
    Casadevall A, Pirofski LA. Adjunctive immune therapy for fungal infections. Clin Infect Dis. 2001;33(7):1048–56.CrossRefGoogle Scholar
  68. 68.
    Liles WC, Huang JE, van Burik JA, Bowden RA, Dale DC. Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens. J Infect Dis. 1997;175(4):1012–5.CrossRefGoogle Scholar
  69. 69.
    Gill AL, Bell CN. Hyperbaric oxygen: its uses, mechanisms of action and outcomes. QJM. 2004;97(7):385–95.CrossRefGoogle Scholar
  70. 70.
    John BV, Chamilos G, Kontoyiannis DP. Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect. 2005;11(7):515–7.CrossRefGoogle Scholar
  71. 71.
    García-Covarrubias L, Barratt DM, Bartlett R, Metzinger S, Van Meter K. Invasive aspergillosis treated with adjunctive hyperbaric oxygenation: a retrospective clinical series at a single institution. South Med J. 2002;95(4):450–6.CrossRefGoogle Scholar
  72. 72.
    Segal E, Menhusen MJ, Shawn S. Hyperbaric oxygen in the treatment of invasive fungal infections: a single-center experience. Isr Med Assoc J. 2007;9(5):355–7.PubMedGoogle Scholar
  73. 73.
    Ibrahim AS, Spellberg B, Edwards J. Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis. 2008;21(6):620–5.CrossRefGoogle Scholar
  74. 74.
    Boelaert JR, de Locht M, Van Cutsem J, et al. Mucormycosis during deferoxamine therapy is a siderophore-mediated infection. In vitro and in vivo animal studies. J Clin Invest. 1993;91(5):1979–86.CrossRefGoogle Scholar
  75. 75.
    Windus DW, Stokes TJ, Julian BA, Fenves AZ. Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine. Ann Intern Med. 1987;107(5):678–80.CrossRefGoogle Scholar
  76. 76.
    Spellberg B, Ibrahim AS, Chin-Hong PV, et al. The Deferasirox-AmBisome therapy for mucormycosis (DEFEAT Mucor) study: a randomized, double-blinded, placebo-controlled trial. J Antimicrob Chemother. 2012;67(3):715–22.CrossRefGoogle Scholar
  77. 77.
    Kontoyiannis DP, Lewis RE. How I treat mucormycosis. Blood. 2011;118(5):1216–24.CrossRefGoogle Scholar
  78. 78.
    Kovanda LL, Kolamunnage-Dona R, Neely M, Maertens J, Lee M, Hope WW. Pharmacodynamics of isavuconazole for invasive mold disease: role of galactomannan for real-time monitoring of therapeutic response. Clin Infect Dis. 2017;64(11):1557–63.CrossRefGoogle Scholar
  79. 79.
    Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32(3):358–66.CrossRefGoogle Scholar
  80. 80.
    Valera FC, do Lago T, Tamashiro E, Yassuda CC, Silveira F, Anselmo-Lima WT. Prognosis of acute invasive fungal rhinosinusitis related to underlying disease. Int J Infect Dis. 2011;15(12):e841–4.CrossRefGoogle Scholar
  81. 81.
    Hachem RY, Boktour MR, Hanna HA, et al. Sinus surgery combined with antifungal therapy is effective in the treatment of invasive Aspergillus sinusitis in neutropenic patients with cancer. Infection. 2008;36(6):539–42.CrossRefGoogle Scholar
  82. 82.
    DelGaudio JM, Clemson LA. An early detection protocol for invasive fungal sinusitis in neutropenic patients successfully reduces extent of disease at presentation and long term morbidity. Laryngoscope. 2009;119(1):180–3.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Infectious DiseasesMedical College of Georgia at Augusta UniversityAugustaUSA
  2. 2.Division of Internal Medicine, Department of Infectious DiseasesThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations