Current Infectious Disease Reports

, Volume 14, Issue 4, pp 423–434 | Cite as

Rhino-Orbital-Cerebral Mucormycosis

  • Maria N. Gamaletsou
  • Nikolaos V. Sipsas
  • Emmanuel Roilides
  • Thomas J. Walsh
Central Nervous System and Eye Infections (KC Bloch, Section Editor)

Abstract

This review focuses on sinus, sino-orbital, and rhinocerebral infection caused by the Mucorales. As the traditional term of “rhinocerebral” mucormycosis omits the critical involvement of the eye, the more comprehensive term as rhino-orbital-cerebral mucormycosis (ROCM) is used. The most common underlying illnesses of ROCM are diabetes mellitus, hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. Sporangiospores are deposited in the nasal turbinates and paranasal sinuses in immunocompromised patients. Qualitative and quantitative abnormalities of neutrophils, monocytes and macrophages increase the risk for development of mucormycosis. Altered iron metabolism also is a critical factor in the pathogenesis of patients with diabetes mellitus who are at risk for ROCM. Angioinvasion with thrombosis and tissue necrosis is a key pathophysiological feature of human Mucorales infection. The ethmoid sinus is a critical site from which sinus mucormycosis may extend through the lamina papyracea into the orbit, extraocular muscles, and optic nerve. The brain may be seeded by invasion of the ethmoidal and orbital veins, which drain into the cavernous sinuses. Diplopia and ophthalmoplegia may be the earliest manifestations of cavernous sinus syndrome before changes are apparent on diagnostic imaging modalities. Negative diagnostic imaging does not exclude cavernous sinus mucormycosis. Mucormycosis of the maxillary sinus has a constellation of clinical features that are different from that of ethmoid sinus mucormycosis. A painful black necrotic ulceration may develop on the hard palate, indicating extension from the maxillary sinus into the oral cavity. Orbital apex syndrome is an ominous complication of mucormycosis of the orbit. Once within the orbital compartment, organisms may extend posteriorly to the optic foramen, where the ophthalmic artery, ophthalmic nerve and optic nerve are threatened by invasion, edema, inflammation and necrosis. Early diagnosis of sinus mucormycosis is critical for prevention of extension to orbital and cerebral tissues. Optimal therapy requires a multidisciplinary approach that relies on prompt institution of appropriate antifungal therapy with amphotericin B, reversal of underlying predisposing conditions, and, where possible, surgical debridement of devitalized tissue. Outcomes are highly dependent upon the degree of immunosuppression, site and extent of infection, timeliness of therapy, and type of treatment provided. New modalities for early diagnosis and therapeutic intervention are critically needed for improved outcome of patients with ROCM.

Keywords

Sinusitis Rhinocerebral mucormycosis Cerebral mucormycosis Orbital mucormycosis 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Walsh TJ, Bloom BE, Kontoyiannis DP. Meeting the challenges of an emerging pathogen: the Henry Schueler 41&9 Foundation International Forum on Mucormycosis. Clin Infect Dis. 2012;54:S1–4.PubMedGoogle Scholar
  2. 2.
    Greenberg RN, Scott LJ, Vaughn HH, Ribes JA. Mucormycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis. 2004;17:517–25.PubMedGoogle Scholar
  3. 3.
    • Park BJ, Pappas PG, Wannemuehler KA, et al. Invasive non-Aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis. 2011;17:1855–64. Important data describing temporal patterns of increasing mucormycosis in transplant patients.PubMedGoogle Scholar
  4. 4.
    Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of mucormycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634–53.PubMedGoogle Scholar
  5. 5.
    • Kwon-Chung KJ. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin Infect Dis. 2012;54:S8–S15. Valuable review of current understanding of nomenclature and molecular taxonomy of mucorales.PubMedGoogle Scholar
  6. 6.
    Lanternier F, Dannaoui E, Morizot G, French Mycosis Study Group, et al. A global analysis of mucormycosis in France: the RetroZygo Study (2005–2007). Clin Infect Dis. 2012;54:S35–43.PubMedGoogle Scholar
  7. 7.
    • Larone D. Identification of medically important fungi. ASM Press; 2012. New edition of important diagnostic text.Google Scholar
  8. 8.
    Gomes MZ, Lewis RE, Kontoyiannis DP. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin Microbiol Rev. 2011;24:411–45.PubMedGoogle Scholar
  9. 9.
    Petraitis V, Petraitiene R, Antachopoulos C, et al. Increased virulence of Cunninghamella bertholetiae in experimental pulmonary mucormycosis: correlation with circulating molecular biomarkers, sporangiospore germination and hyphal metabolism. Medical Mycol (in press).Google Scholar
  10. 10.
    O'Connell MA, Pluss JL, Schkade P, et al. Rhizopus-induced hypersensitivity pneumonitis in a tractor driver. J Allergy Clin Immunol. 1995;95:779–80.PubMedGoogle Scholar
  11. 11.
    Spellberg B, Edwards Jr J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18:556–69.PubMedGoogle Scholar
  12. 12.
    Levitz SM, Selsted ME, Ganz T, et al. 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.PubMedGoogle Scholar
  13. 13.
    • Roilides E, Kontoyiannis DP, Walsh TJ. Host defenses against Zygomycetes. Clin Infect Dis. 2012;54 Suppl 1:S61–6. Comprehensive review of innate host defenses against mucorales.Google Scholar
  14. 14.
    Diamond RD, Clark RA. Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. Infect Immun. 1982;38:487–95.PubMedGoogle Scholar
  15. 15.
    Waldorf AR, Levitz SM, Diamond RD. In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus. J Infect Dis. 1984;150:752–60.PubMedGoogle Scholar
  16. 16.
    Waldorf AR, Ruderman N, Diamond RD. Specific susceptibility to mucomycosis in murine diabetes and bronchoalveolar macrophage defense against Rhizopus. J Clin Invest. 1984;74:150–60.PubMedGoogle Scholar
  17. 17.
    Mowat A, Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med. 1971;284:621–7.PubMedGoogle Scholar
  18. 18.
    Bagdade JD. Phagocytic and microbicidal function in diabetes mellitus. Acta Endocrinol Suppl (Copenh). 1976;205:27–34.Google Scholar
  19. 19.
    Bybee JD, Rogers DE. The phagocytic activity of polymorphonuclear leukocytes obtained from patients with diabetes mellitus. J Lab Clin Med. 1964;64:1–13.PubMedGoogle Scholar
  20. 20.
    Baldwin DA, De Sousa DM, Von Wandruszka RM. The effect of pH on the kinetics of iron release from human transferrin. Biochim Biophys Acta. 1982;719:140–6.PubMedGoogle Scholar
  21. 21.
    Artis WM, Fountain JA, Delcher HK, Jones HE. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes. 1982;31:1109–14.PubMedGoogle Scholar
  22. 22.
    Espinoza CG, Halkias DG. Pulmonary mucormycosis as a complication of chronic salicylate poisoning. Am J Clin Pathol. 1983;80:508–11.PubMedGoogle Scholar
  23. 23.
    Lewis LL, Hawkins HK, Edwards MS. Disseminated mucormycosis in an infant with methylmalonicaciduria. Pediatr Infect Dis J. 1990;9:851–4.PubMedGoogle Scholar
  24. 24.
    Ibrahim A, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis. 2012;54:S16–22.PubMedGoogle Scholar
  25. 25.
    de Locht M, Boelaert JR, Schneider YJ. Iron uptake from ferrioxamine and from ferrirhizoferrin by germinating spores of Rhizopus microsporus. Biochem Pharmacol. 1994;47:1843–50.PubMedGoogle Scholar
  26. 26.
    Boelaert JR, Fenves AZ, Coburn JW. Deferoxamine therapy and mucormycosis in dialysis patients: report of an international registry. Am J Kidney Dis. 1991;18:660–7.PubMedGoogle Scholar
  27. 27.
    Boelaert JR, van Roost GF, Vergauwe PL, et al. The role of desferrioxamine in dialysis-associated mucomycosis: report of three cases and review of the literature. Clin Nephrol. 1988;29:261–6.PubMedGoogle Scholar
  28. 28.
    Maertens J, Demuynck H, Verbeken EK, et al. Mucormycosis in allogeneic bone marrow transplant recipients: report of five cases and review of the role of iron overload in the pathogenesis. Bone Marrow Transplant. 1999;24:307–12.PubMedGoogle Scholar
  29. 29.
    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;91:1979–86.PubMedGoogle Scholar
  30. 30.
    Ibrahim AS, Spellberg B, Avanessian V, et al. Rhizopus oryzae adheres to, is phagocytosed by, and damages endothelial cells in vitro. Infect Immun. 2005;73:778–83.PubMedGoogle Scholar
  31. 31.
    Chamilos G, Russell LE, Jianhua H, et al. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Natl Acad Sci U S A. 2008;105:9367–72.PubMedGoogle Scholar
  32. 32.
    van de Veerdonk FL, Kullberg BJ, van der Meer JW, et al. Host-microbe interactions: innate pattern recognition of fungal pathogens. Curr Opin Microbiol. 2008;11:305–12.PubMedGoogle Scholar
  33. 33.
    Chamilos G, Lewis RE, Lamaris G, et al. Zygomycetes hyphae trigger an early, robust proinflammatory response in human polymorphonuclear neutrophils through toll-like receptor 2 induction but display relative resistance to oxidative damage. Antimicrob Agents Chemother. 2008;52:722–4.PubMedGoogle Scholar
  34. 34.
    Netea MG, Van der Meer JW, Kullberg BJ. Role of the dual interaction of fungal pathogens with pattern recognition receptors in the activation and modulation of host defence. Clin Microbiol Infect. 2006;12:404–9.PubMedGoogle Scholar
  35. 35.
    Warris A, Netea MG, Verweij PE, et al. Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi. Med Mycol. 2005;43:613–21.PubMedGoogle Scholar
  36. 36.
    Cortez KJ, Lyman CA, Lempicki R, et al. Comparative functional genomics of innate host defense molecules in human monocytes infected with Aspergillus fumigatus and Rhizopus Oryzae (abstr M-1773/393). In 46th Interscience Conference Antimicrob. Agents Chemother. San Francisco CA; 2006.Google Scholar
  37. 37.
    Gil-Lamaignere C, Simitsopoulou M, Roilides E, et al. Interferon- gamma and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J Infect Dis. 2005;191:1180–7.PubMedGoogle Scholar
  38. 38.
    Simitsopoulou M, Georgiadou E, Walsh TJ, Roilides E. Cunninghamella bertholetiae exhibits increased resistance to human neutrophils with or without antifungal agents as compared to Rhizopus spp. Med Mycol. 2010;48:720–4.PubMedGoogle Scholar
  39. 39.
    Rees JR, Pinner RW, Hajjeh RA, et al. The epidemiological features of invasive mycotic infections in the San Francisco Bay Area, 1992–1993: Results of population- based laboratory active surveillance. Clin Infect Dis. 1998;27:1138–47.PubMedGoogle Scholar
  40. 40.
    Kontoyiannis DP. Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis. 2007;44:1089–90.PubMedGoogle Scholar
  41. 41.
    Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KVI. Mucormycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis. 2000;30:851–6.PubMedGoogle Scholar
  42. 42.
    Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909–17.PubMedGoogle Scholar
  43. 43.
    • Lewis RE, Liao G, Wang W, et al. Voriconazole pre-exposure selects for breakthrough mucormycosis in a mixed model of Aspergillus fumigatus-Rhizopus oryzae pulmonary infection. Virulence. 2011;2:348–55. Valuable study of mechanisms of voriconazole in selecting for Rhizopus oryzae.PubMedGoogle Scholar
  44. 44.
    Imhof A, Balajee SA, Fredricks DN, et al. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis. 2004;39:743–6.PubMedGoogle Scholar
  45. 45.
    Kontoyiannis DP, Lionakis MS, Lewis RE, et al. Mucormycosis 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;191:1350–60.PubMedGoogle Scholar
  46. 46.
    Marty FM, Cosimi LA, Baden LR. Breakthrough mucormycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med. 2004;350:950–2.PubMedGoogle Scholar
  47. 47.
    Oren H. Breakthrough mucormycosis during empirical voriconazole therapy in febrile patients with neutropenia. Clin Infect Dis. 2005;40:770–1.PubMedGoogle Scholar
  48. 48.
    Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, et al. Invasive mucormycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis. 2004;39:584–7.PubMedGoogle Scholar
  49. 49.
    Vigouroux S, Morin O, Moreau P, et al. Mucormycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: Attention required. Clin Infect Dis. 2005;40:E35–7.PubMedGoogle Scholar
  50. 50.
    Wingard JR, Carter SL, Walsh TJ, et al. Randomized, double-blind trial of fluconazole vs. voriconazole for the prevention of invasive fungal disease after allogeneic hematopoietic cell transplantation. Blood. 2010;116:5111–8.PubMedGoogle Scholar
  51. 51.
    Diwakar A, Dewan RK, Chowdhary A, Randhawa HS, Khanna G, Gaur SN. Mucormycosis–a case report and overview of the disease in India. Mycoses. 2007;50:247–54.PubMedGoogle Scholar
  52. 52.
    Anaissie EJ, Shikhani AH. Rhinocerebral mucormycosis with internal carotid occlusion: report of two cases and review of the literature. Laryngoscope. 1985;95:1107–13.PubMedGoogle Scholar
  53. 53.
    Peterson KL, Wang M, Canalis RF, Abemayor E. Rhinocerebral mucormycosis: evolution of the disease and treatment options. Laryngoscope. 1997;107:855–62.PubMedGoogle Scholar
  54. 54.
    Varghese A, Thomas S. Orbital apex syndrome secondary to mucormycosis after a tooth extraction in an immunocompetent patient. Ear Nose Throat J. 2010;89:E24–6.PubMedGoogle Scholar
  55. 55.
    Feeley MA, Righi PD, Davis TE, Greist A. Mucormycosis of the paranasal sinuses and septum. Otolaryngol Head Neck Surg. 1999;120:750.PubMedGoogle Scholar
  56. 56.
    Humphry RC, Wright G, Rich WJ, Simpson R. Acute proptosis and blindness in a patient with orbital phycomycosis. J R Soc Med. 1989;82:304–5.PubMedGoogle Scholar
  57. 57.
    Parthiban K, Gnanaguruvelan S, Janaki C, et al. Rhinocerebral mucormycosis. Mycoses. 1998;41:51–3.PubMedGoogle Scholar
  58. 58.
    Anand VK, Alemar G, Griswold Jr JA. Intracranial complications of mucormycosis: an experimental model and clinical review. Laryngoscope. 1992;102:656–62.PubMedGoogle Scholar
  59. 59.
    Gokcil Z, Odabasi Z, Kutukcu Y, et al. Rhino-orbito-cerebral mucormycosis. J Neurol. 1998;245:689–90.PubMedGoogle Scholar
  60. 60.
    Smith JL, Stevens DA. Survival in cerebro-rhino-orbital mucormycosis and cavernous sinus thrombosis with combined therapy. South Med J. 1986;79:501–4.PubMedGoogle Scholar
  61. 61.
    Galetta SL, Wulc AE, Goldberg HI, et al. Rhinocerebral mucormycosis: management and survival after carotid occlusion. Ann Neurol. 1990;28:103–7.PubMedGoogle Scholar
  62. 62.
    Chawla B, Sharma S, Kashyap S, Kabra SK, Pushker N, Bajaj MS. Primary orbital mycosis in immunocompetent infants. J AAPOS. 2011;15:211–3.PubMedGoogle Scholar
  63. 63.
    Mbarek C, Zribi S, Khamassi K, Hariga I, Ouni H, Ben Amor M, Ben Gamra O, El Khedim A. Rhinocerebral mucormycosis: five cases and a literature review. B-ENT. 2011;7:189–93.PubMedGoogle Scholar
  64. 64.
    Ketenci I, Unlü Y, Kaya H, Somdaş MA, Kontaş O, Oztürk M, Vural A. Rhinocerebral mucormycosis: experience in 14 patients. J Laryngol Otol. 2011;125:e3.PubMedGoogle Scholar
  65. 65.
    Lazo A, Wilner HI, Metes JJ. Craniofacial mucormycosis: computed tomographic and angiographic findings in two cases. Radiology. 1981;139:623–6.PubMedGoogle Scholar
  66. 66.
    Greenberg MR, Lippman SM, Grinnell VS, Colman MF, Edwards Jr JE. Computed tomographic findings in orbital Mucor. West J Med. 1985;143:102–3.PubMedGoogle Scholar
  67. 67.
    Press GA, Weindling SM, Hesselink JR, Ochi JW, Harris JP. Rhinocerebral mucormycosis: MR manifestations. J Comput Assist Tomogr. 1988;12:744–9.PubMedGoogle Scholar
  68. 68.
    Deshazo RD. Syndromes of invasive fungal sinusitis. Med Mycol. 2009;47:S309–14.PubMedGoogle Scholar
  69. 69.
    Yeh S, Foroozan R. Orbital apex syndrome. Curr Opin Ophthalmol. 2004;15:490–8.PubMedGoogle Scholar
  70. 70.
    René C. Update on orbital anatomy. Eye. 2006;20:1119–29.PubMedGoogle Scholar
  71. 71.
    Karakurum B, Karatas M, Cagici AC, et al. Mucormycosis presenting with painful ophthalmoplegia. Acta Neurol Belg. 2005;105:201–5.PubMedGoogle Scholar
  72. 72.
    Balch K, Phillips PH, Newman NJ. Painless orbital apex syndrome from mucormycosis. J Neuroophthalmol. 1997;17:178–82.PubMedGoogle Scholar
  73. 73.
    Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden R, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary and disseminated mucormycosis (zygomycosis). Clin Infect Dis. 2012;54 Suppl 1:S55–60.PubMedGoogle Scholar
  74. 74.
    Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with Hematologic malignancy who have mucormycosis. Clin Infect Dis. 2008;47:503–9.PubMedGoogle Scholar
  75. 75.
    Monheit JE, Cowan DF, Moore DG. Rapid detection of fungi in tissues using calcofluor white and fluorescence microscopy. Arch Pathol Lab Med. 1984;108:616–8.PubMedGoogle Scholar
  76. 76.
    McDermott NE, Barrett J, Hipp J, et al. Successful treatment of periodontal mucormycosis: report of a case and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:e64–9.PubMedGoogle Scholar
  77. 77.
    Kasai M, Harrington SM, Francesconi A, et al. Detection of a molecular biomarker for zygomycetes by quantitative PCR assays of plasma, bronchoalveolar lavage, and lung tissue in a rabbit model of experimental pulmonary mucormycosis. J Clin Microbiol. 2008;46:3690–702.PubMedGoogle Scholar
  78. 78.
    Blitzer A, Lawson W, Meyers BR, Biller HF. Patient survival factors in paranasal sinus mucormycosis. Laryngoscope. 1980;90:635–48.PubMedGoogle Scholar
  79. 79.
    Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol. 1994;39:3–22.PubMedGoogle Scholar
  80. 80.
    Antachopoulos C, Meletiadis J, Roilides E, et al. Rapid susceptibility testing of medically important zygomycetes by XTT assay. J Clin Microbiol. 2006;44:553–60.PubMedGoogle Scholar
  81. 81.
    Espinel-Ingroff A. In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J Clin Microbiol. 2001;39:954–8.PubMedGoogle Scholar
  82. 82.
    Odds FC, van Gerven F, Espinel-Ingroff A, et al. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother. 1998;42:282–8.PubMedGoogle Scholar
  83. 83.
    Otcenasek M, Buchta V. In vitro susceptibility to 9 antifungal agents of 14 strains of Zygomycetes isolated from clinical specimens. Mycopathologia. 1994;128:135–7.PubMedGoogle Scholar
  84. 84.
    Pfaller MA, Marco F, Messer SA, Jones RN. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis. 1998;30:251–5.PubMedGoogle Scholar
  85. 85.
    Van Cutsem J, Van Gerven F, Fransen J, Janssen PA. Treatment of experimental mucormycosis in guinea pigs with azoles and with amphotericin B. Chemotherapy. 1989;35:267–72.PubMedGoogle Scholar
  86. 86.
    Watson DC, Neame PB. In vitro activity of amphotericin B on strains of Mucoraceae pathogenic to man. J Lab Clin Med. 1960;56:251–7.PubMedGoogle Scholar
  87. 87.
    Spellberg B, Fu Y, Edwards Jr JE, Ibrahim AS. Combination therapy with amphotericin B lipid complex and caspofungin acetate of disseminated mucormycosis in diabetic ketoacidotic mice. Antimicrob Agents Chemother. 2005;49:830–2.PubMedGoogle Scholar
  88. 88.
    Ibrahim AS, Gebremariam T, Fu Y, et al. Combination echinocandin-polyene treatment of murine mucormycosis. Antimicrob Agents Chemother. 2008;52:1556–8.PubMedGoogle Scholar
  89. 89.
    Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital- cerebral mucormycosis. Clin Infect Dis. 2008;47:364–71.PubMedGoogle Scholar
  90. 90.
    Dannaoui E, Meletiadis J, Mouton JW, et al. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother. 2003;51:45–52.PubMedGoogle Scholar
  91. 91.
    Dannaoui E, Afeltra J, Meis J, Verweij PE. In vitro susceptibilities of zygomycetes to combinations of antimicrobial agents. Antimicrob Agents Chemother. 2002;46:2708–11.PubMedGoogle Scholar
  92. 92.
    Singh J, Rimek D, Kappe R. In vitro susceptibility of 15 strains of zygomycetes to nine antifungal agents as determined by the NCCLS M38-A microdilution method. Mycoses. 2005;48:246–50.PubMedGoogle Scholar
  93. 93.
    Sun QN, Fothergill AW, McCarthy DI, et al. In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother. 2002;46:1581–2.PubMedGoogle Scholar
  94. 94.
    Gaviria JM, Grohskopf LA, Barnes R, Root RK. Successful treatment of rhinocerebral mucormycosis: a combined- strategy approach. Clin Infect Dis. 1999;28:160–1.PubMedGoogle Scholar
  95. 95.
    Gaziev D, Baronciani D, Galimberti M, et al. Mucormycosis after bone marrow transplantation: report of four cases in thalassemia and review of the literature. Bone Marrow Transplant. 1996;17:409–14.PubMedGoogle Scholar
  96. 96.
    Gleissner B, Schilling A, Anagnostopolous I, et al. Improved outcome of mucormycosis in patients with hematological diseases? Leuk Lymphoma. 2004;45:1351–60.PubMedGoogle Scholar
  97. 97.
    Hunstad DA, Cohen AH, St Geme 3rd JW. Successful eradication of mucormycosis occurring in a pulmonary allograft. J Heart Lung Transplant. 1999;18:801–4.PubMedGoogle Scholar
  98. 98.
    Leleu X, Sendid B, Fruit J, et al. Combined anti-fungal therapy and surgical resection as treatment of pulmonary mucormycosis in allogeneic bone marrow transplantation. Bone Marrow Transplant. 1999;24:417–20.PubMedGoogle Scholar
  99. 99.
    Linden P, Williams P, Chan KM. Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid-organ transplant recipients with invasive fungal infections. Clin Transplant. 2000;14:329–39.PubMedGoogle Scholar
  100. 100.
    Maury S, Leblanc T, Feuihade M, Molina J-M, Schaison G. Successful treatement of disseminated mucormycosis with liposomal amphotericin B and surgery in a child with leukemia. Clin Infect Dis. 1998;26:200–2.PubMedGoogle Scholar
  101. 101.
    Mazade MA, Margolin JF, Rossmann SN, Edwards MS. Survival from pulmonary infection with Cunninghamella bertholletiae: case report and review of the literature. Pediatr Infect Dis J. 1998;17:835–9.PubMedGoogle Scholar
  102. 102.
    Meis JF, Kullberg BJ, Pruszczynski M, Veth RP. Severe osteomyelitis due to the zygomycete Apophysomyces elegans. J Clin Microbiol. 1994;32:3078–81.PubMedGoogle Scholar
  103. 103.
    Moses AE, Rahav G, Barenholz Y, et al. Rhinocerebral mucormycosis treated with amphotericin B colloidal dispersion in three patients. Clin Infect Dis. 1998;26:1430–3.PubMedGoogle Scholar
  104. 104.
    Nenoff P, Kellermann S, Schober R, et al. Rhinocerebral mucormycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature. Mycoses. 1998;41:365–72.PubMedGoogle Scholar
  105. 105.
    Okhuysen PC, Rex JH, Kapusta M, Fife C. Successful treatment of extensive posttraumatic soft-tissue and renal infections due to Apophysomyces elegans. Clin Infect Dis. 1994;19:329–31.PubMedGoogle Scholar
  106. 106.
    Saltoglu N, Tasova Y, Zorludemir S, Dundar IH. Rhinocerebral mucormycosis treated with liposomal amphotericin B and surgery. Mycoses. 1998;41:45–9.PubMedGoogle Scholar
  107. 107.
    St-Germain G, Robert A, Ishak M, et al. Infection due to Rhizomucor pusillus: report of four cases in patients with leukemia and review. Clin Infect Dis. 1993;16:640–5.PubMedGoogle Scholar
  108. 108.
    Strasser MD, Kennedy RJ, Adam RD. Rhinocerebral mucormycosis. Therapy with amphotericin B lipid complex. Arch Intern Med. 1996;156:337–9.PubMedGoogle Scholar
  109. 109.
    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.PubMedGoogle Scholar
  110. 110.
    Shoham S, Magill SS, Merz WG, et al. Primary treatment of mucormycosis with liposomal amphotericin B: analysis of 28 cases. Med Mycol. 2010;48:511–7.PubMedGoogle Scholar
  111. 111.
    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.PubMedGoogle Scholar
  112. 112.
    Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents - pharmacokinetics, safety and efficacy. Drugs. 2004;64:1997–2020.PubMedGoogle Scholar
  113. 113.
    Sun QN, Najvar LK, Bocanegra R, et al. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother. 2002;46:2310–2.PubMedGoogle Scholar
  114. 114.
    Diekema DJ, Messer SA, Hollis RJ, et al. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol. 2003;41:3623–6.PubMedGoogle Scholar
  115. 115.
    Eisen DP, Robson J. Complete resolution of pulmonary Rhizopus oryzae infection with itraconazole treatment: more evidence of the utility of azoles for mucormycosis. Mycoses. 2004;47:159–62.PubMedGoogle Scholar
  116. 116.
    Mathew R, Kumaravel S, Kuruvilla S, et al. Successful treatment of extensive basidiobolomycosis with oral itraconazole in a child. Int J Dermatol. 2005;44:572–5.PubMedGoogle Scholar
  117. 117.
    Quinio D, Karam A, Leroy JP, et al. Mucormycosis caused by Cunninghamella bertholletiae in a kidney transplant recipient. Med Mycol. 2004;42:177–80.PubMedGoogle Scholar
  118. 118.
    Dannaoui E, Meis J, Loebenberg D, Verweij PE. Activity of posaconazole in treatment of experimental disseminated mucormycosis. Antimicrob Agents Chemother. 2003;47:3647–50.PubMedGoogle Scholar
  119. 119.
    Rodriguez MM, Serena C, Marine M, et al. Posaconazole combined with amphotericin B, an effective therapy for a murine disseminated infection caused by Rhizopus oryzae. Antimicrob Agents Chemother. 2008;52:3786–8.PubMedGoogle Scholar
  120. 120.
    Ibrahim AS, Gebremariam T, Schwartz JA, et al. Posaconazole mono- or combination therapy for treatment of murine mucormycosis. Antimicrob Agents Chemother. 2009;53:772–5.PubMedGoogle Scholar
  121. 121.
    Van Burik JAH, Hare RS, Solomon HF, et al. Posaconazole is effective as salvage therapy in mucormycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42:E61–5.PubMedGoogle Scholar
  122. 122.
    Greenberg RN, Mullane K, van Burik JA, et al. Posaconazole as salvage therapy for mucormycosis. Antimicrob Agents Chemother. 2006;50:126–33.PubMedGoogle Scholar
  123. 123.
    Brugiere O, Dauriat G, Mal H, et al. Pulmonary mucormycosis (mucormycosis) in a lung transplant recipient: recovery after posaconazole therapy. Transplantation. 2005;80:544–5.PubMedGoogle Scholar
  124. 124.
    Garbino J, Uckay I, Amini K, et al. Absidia posttraumatic infection: successful treatment with posaconazole. J Infect. 2005;51:e135–8.PubMedGoogle Scholar
  125. 125.
    Tobon AM, Arango M, Fernandez D, Restrepo A. Mucormycosis (Mucormycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis. 2003;36:1488–91.PubMedGoogle Scholar
  126. 126.
    Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards Jr J, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009;48:1743–51.PubMedGoogle Scholar
  127. 127.
    Ibrahim AS, Gebermariam T, Fu Y, et al. The iron chelator deferasirox protects mice from mucormycosis through iron starvation. J Clin Invest. 2007;117:2649–57.PubMedGoogle Scholar
  128. 128.
    Reed C, Ibrahim A, Edwards Jr JE, et al. Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob Agents Chemother. 2006;50:3968–9.PubMedGoogle Scholar
  129. 129.
    Caldwell J. Effects of high partial pressures of oxygen on fungi. Nature. 1963;197:772–4.Google Scholar
  130. 130.
    Karsner HT, Saphir O. Influence of high partial pressures of oxygen on the growth of certain molds. J Infect Dis. 1926;39:231–6.Google Scholar
  131. 131.
    Robb SM. Reactions of fungi to exposure to 10 atmospheres pressure of oxygen. J Gen Microbiol. 1966;45:17–29.Google Scholar
  132. 132.
    Bentur Y, Shupak A, Ramon Y, et al. Hyperbaric oxygen therapy for cutaneous/soft-tissue mucormycosis complicating diabetes mellitus. Plast Reconstr Surg. 1998;102:822–4.PubMedGoogle Scholar
  133. 133.
    Couch L, Theilen F, Mader JT. Rhinocerebral mucormycosis with cerebral extension successfully treated with adjunctive hyperbaric oxygen therapy. Arch Otolaryngol Head Neck Surg. 1988;114:791–4.PubMedGoogle Scholar
  134. 134.
    De La Paz MA, Patrinely JR, Marines HM, Appling WD. Adjunctive hyperbaric oxygen in the treatment of bilateral cerebro-rhino-orbital mucormycosis. Am J Ophthalmol. 1992;114:208–11.Google Scholar
  135. 135.
    Gonzalez CE, Couriel DR, Walsh TJ. Disseminated mucormycosis in a neutropenic patient: successful treatment with amphotericin B lipid complex and granuloyte colony-stimulating factor. Clin Infect Dis. 1997;24:192–6.PubMedGoogle Scholar
  136. 136.
    Quillen K, Wong E, Scheinberg P, et al. Granulocyte transfusions in severe aplastic anemia: an 11-year experience. Haematologica. 2009;94:1661–8.PubMedGoogle Scholar
  137. 137.
    Liles WC, Huang JE, van Burik J-AH, et al. Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens. J Infect Dis. 1997;175:1012–5.PubMedGoogle Scholar
  138. 138.
    Mayer P, Schutze E, Lam C, et al. Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice. J Infect Dis. 1991;163:584–90.PubMedGoogle Scholar
  139. 139.
    Romani L. Immunity to fungal infections. Nat Rev Immunol. 2004;4:11–23.Google Scholar
  140. 140.
    Pursell K, Verral S, Daraiesh F, et al. Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens in transplant recipients: in vitro effect of r-metHuG-CSF (Filgrastim). Transpl Infect Dis. 2003;5:29–37.PubMedGoogle Scholar
  141. 141.
    Antachopoulos C, Roilides E. Cytokines and fungal infections. Br J Haematol. 2005;129:583–96.PubMedGoogle Scholar
  142. 142.
    Brandt SJ, Peters WP, Atwater SK, et al. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med. 1988;318:869–76.PubMedGoogle Scholar
  143. 143.
    Yoshida T, Nakamura S, Ohtake S, et al. Effect of granulocyte colony-stimulating factor on neutropenia due to chemotherapy for non-Hodgkin’s lymphoma. Cancer. 1990;66:1904–9.PubMedGoogle Scholar
  144. 144.
    Abzug MJ, Walsh TJ. Interferon-gamma and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. Pediatr Infect Dis J. 2004;23:769–73.PubMedGoogle Scholar
  145. 145.
    Sahin B, Paydas S, Cosar E, et al. Role of granulocyte colony-stimulating factor in the treatment of mucormycosis. Eur J Clin Microbiol Infect Dis. 1996;15:866–9.PubMedGoogle Scholar
  146. 146.
    Bhatia S, McCullough J, Perry EH, et al. Granulocyte transfusion: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation. Transfusion. 1994;34:226–32.PubMedGoogle Scholar
  147. 147.
    Hester JP, Dignani MC, Anaissie EJ, et al. Collection and transfusion of granulocyte concentrates from donors primed with granulocyte stimulating factor and response of myelosuppressed patients with established infection. J Clin Apher. 1995;10:188–93.PubMedGoogle Scholar
  148. 148.
    Dignani MC, Anaissie EJ, Hester JP, et al. Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions: a pilot study. Leukemia. 1997;11:1621–30.PubMedGoogle Scholar
  149. 149.
    Jendiroba DB, Lichtiger B, Anaissie E, et al. Evaluation and comparison of three mobilization methods for the collection of granulocytes. Transfusion. 1998;38:722–8.PubMedGoogle Scholar
  150. 150.
    Briones MA, Josephson CD, Hillyer CD. Granulocyte transfusion: revisited. Curr Hematol Rep. 2003;2:522–7.PubMedGoogle Scholar
  151. 151.
    Anaissie EJ. Diagnosis and therapy of fungal infection in patients with leukemia–new drugs and immunotherapy. Best Pract Res Clin Haematol. 2008;21:683–90.PubMedGoogle Scholar
  152. 152.
    Langford JD, McCartney DL, Wang RC. Frozen section–guided surgical debridement for management of rhino-orbital mucormycosis. Am J Ophthalmol. 1997;124:265–7.PubMedGoogle Scholar
  153. 153.
    Abedi E, Sismanis A, Choi K, Pastore P. Twenty-five years’ experience treating cerebro-rhino-orbital mucormycosis. Laryngoscope. 1984;94:1060–2.PubMedGoogle Scholar
  154. 154.
    Gupta AK, Mann SB, Khosla VK, et al. Non-randomized comparison of surgical modalities for paranasal sinus mycoses with intracranial extension. Mycoses. 1999;42:225–30.PubMedGoogle Scholar
  155. 155.
    Pelton RW, Peterson EA, Patel BC, Davis K. Successful treatment of rhino-orbital mucormycosis without exenteration: the use of multiple treatment modalities. Ophthal Plast Reconstr Surg. 2001;17:62–6.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Maria N. Gamaletsou
    • 1
  • Nikolaos V. Sipsas
    • 1
  • Emmanuel Roilides
    • 2
  • Thomas J. Walsh
    • 3
  1. 1.Pathophysiology Department, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  2. 2.3rd Department of PediatricsAristotle University School of Medicine, Hippokration HospitalThessalonikiGreece
  3. 3.Transplantation-Oncology Infectious Diseases ProgramWeill Cornell Medical Center of Cornell UniversityNew YorkUSA

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