Semin Respir Crit Care Med 2004; 25(2): 221-231
DOI: 10.1055/s-2004-824905
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Zygomycosis

Alison G. Freifeld1 , Peter C. Iwen2
  • 1Infectious Diseases Section, Department of Medicine, Omaha, Nebraska
  • 2Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska
Further Information

Publication History

Publication Date:
19 April 2004 (online)

Zygomycosis is an invasive mycotic disease caused by fungi in the class Zygomycetes. Within this class, the most common species associated with infection include Absidia corymbifera, Apophysomyces elegans, Cunninghamella bertholletiae, Rhizomucor pusillus, Rhizopus microsporus var. rhizopodiformis, and Rhizopus arrhizus. These fungi all produce characteristic hyphal forms in tissue that are variable in width, produce haphazard branching, and lack septation. Although these fungi are ubiquitous in the environment, they are opportunists causing invasive disease in compromised hosts with a high mortality even when aggressive antifungal therapy and surgical intervention are utilized. Clinically, the disease most often affects the sinus with or without pulmonary involvement; direct extension from sinuses into cerebral tissue is not uncommon. This article describes the general clinical features of zygomycosis, with an emphasis on management in the setting of immunosuppression.

REFERENCES

  • 1 Lee F Y, Mossad S B, Adal K A. Pulmonary mucormycosis: the last 30 years.  Arch Intern Med. 1999;  159 1301-1309
  • 2 Kwon-Chung K J, Bennett J E. Mucormycosis. In: Cann C Medical Mycology. Philadelphia; Lea & Febiger 1992: 524-559
  • 3 Ribes J A, Vanover-Sams C L, Baker D J. Zygomycetes in human disease.  Clin Microbiol Rev. 2000;  13 236-301
  • 4 Sugar A. Agents of mucormycosis and related species. In: Mandell GL, Bennett JE, Dolin R Principles and Practice of Infectious Diseases. Vol 2. 5th ed. Philadelphia; Churchill Livingstone; 2000: 2685-2694
  • 5 Belin L. Sawmill alveolitis in Sweden.  Int Arch Allergy Appl Immunol. 1987;  82 440-443
  • 6 Wimander K, Belin L. Recognition of allergic alveolitis in the trimming department of a Swedish sawmill.  Eur J Respir Dis Suppl. 1980;  107 163-167
  • 7 Waldorf A R. Pulmonary defense mechanisms against opportunistic fungal pathogens.  Immunol Ser. 1989;  47 243-271
  • 8 Diamond R D, Clark R A. Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro.  Infect Immun. 1982;  38 487-495
  • 9 Waldorf A R, Ruderman N, Diamond R D. Specific susceptibility of mucormycosis in murine diabetes and broncholaveolar macrophage defense against Rhizopus .  J Clin Invest. 1984;  74 150-160
  • 10 Artis W M, Fountain J A, Delcher H K, Jones H E. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability.  Diabetes. 1982;  31 1109-1114
  • 11 Bagdade J D. Phagocytic and microbicidal function in diabetes mellitus.  Acta Endocrinol Suppl (Copenh). 1976;  205 27-34
  • 12 Meyer R D, Rosen P, Armstrong D. Phycomycosis complicating leukemia and lymphoma.  Ann Intern Med. 1972;  77 871-879
  • 13 Kontoyiannis D P, Wessel V C, Bodey G P, Rolston K V. Zygomycosis in the 1990s in a tertiary-care cancer center.  Clin Infect Dis. 2000;  30 851-856
  • 14 Marr K A, Carter R A, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients.  Clin Infect Dis. 2002;  34 909-917
  • 15 Windus D W, Stokes T J, Julian B A, Fenves A Z. Fatal Rhizopus infections in hemodialysis patients receiving deferoxamine.  Ann Intern Med. 1987;  107 678-680
  • 16 Daly A L, Velazquez L A, Bradley S F, Kauffman C A. Mucormycosis: association with deferoxamine therapy.  Am J Med. 1989;  87 468-471
  • 17 Eiser A R, Slifkin R F, Neff M S. Intestinal mucormycosis in hemodialysis patients following deferoxamine.  Am J Kidney Dis. 1987;  10 71-73
  • 18 Singh N, Gayowski T, Singh J, Yu V L. Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report and review of zygomycosis in solid-organ transplant recipients.  Clin Infect Dis. 1995;  20 617-620
  • 19 Paparello S F, Parry R L, MacGillivray D C, Brock N, Mayers D L. Hospital-acquired wound mucormycosis.  Clin Infect Dis. 1992;  14 350-352
  • 20 Song W K, Park H J, Cinn Y W et al.. Primary cutaneous mucormycosis in a trauma patient.  J Dermatol. 1999;  26 825-828
  • 21 Sharma R R, Pawar S J, Delmendo A, Lad S D, Athale S D. Fatal rhino-orbito-cerebral mucormycosis in an apparently normal host: case report and literature review.  J Clin Neurosci. 2001;  8 583-586
  • 22 Mitchell S J, Gray J, Morgan M E, Hocking M D, Durbin G M. Nosocomial infection with Rhizopus microsporus in preterm infants: association with wooden tongue depressors.  Lancet. 1996;  348 441-443
  • 23 Oh D, Notrica D. Primary cutaneous mucormycosis in infants and neonates: case report and review of the literature.  J Pediatr Surg. 2002;  37 1607-1611
  • 24 Hejny C, Kerrison J B, Newman N J, Stone C M. Rhino-orbital mucormycosis in a patient with acquired immunodeficiency syndrome (AIDS) and neutropenia.  Am J Ophthalmol. 2001;  132 111-112
  • 25 Sanchez M R, Ponge-Wilson I, Moy J A, Rosenthal S. Zygomycosis and HIV infection.  J Am Acad Dermatol. 1994;  30(5 pt 2) 904-908
  • 26 Gonzalez C E, Rinaldi M G, Sugar A M. Zygomycosis.  Infect Dis Clin North Am. 2002;  16 895-914
  • 27 Rangel-Guerra R A, Martinez H R, Saenz C, Bosques-Padilla F, Estrada-Bellmann I. Rhinocerebral and systemic mucormycosis: clinical experience with 36 cases.  J Neurol Sci. 1996;  143 19-30
  • 28 Pagano L, Ricci P, Tonso A et al.. Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. GIMEMA Infection Program (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto).  Br J Haematol. 1997;  99 331-336
  • 29 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;  17 409-414
  • 30 Ferguson B J. Mucormycosis of the nose and paranasal sinuses.  Otolaryngol Clin North Am. 2000;  33 349-365
  • 31 Sohail M A, Al Khabori M, Hyder J, Verma A. Acute fulminant fungal sinusitis: clinical presentation, radiological findings and treatment.  Acta Trop. 2001;  80 177-185
  • 32 Kyrmizakis D E, Doxas P G, Hajiioannou J K, Papadakis C E. Palate ulcer due to mucormycosis.  J Laryngol Otol. 2002;  116 146-147
  • 33 Blitzer A, Lawson W, Meyers B R, Biller H F. Patient survival factors in paranasal sinus mucormycosis.  Laryngoscope. 1980;  90 635-648
  • 34 Tedder M, Spratt J A, Anstadt M P et al.. Pulmonary mucormycosis: results of medical and surgical therapy.  Ann Thorac Surg. 1994;  57 1044-1050
  • 35 Latif S, Saffarian N, Bellovich K, Provenzano R. Pulmonary mucormycosis in diabetic renal allograft recipients.  Am J Kidney Dis. 1997;  29 461-464
  • 36 Demirag A, Elkhammas E A, Henry M L et al.. Pulmonary Rhizopus infection in a diabetic renal transplant recipient.  Clin Transplant. 2000;  14 8-10
  • 37 Veliath A J, Rao R, Prabhu M R, Aurora A L. Cutaneous phycomycosis (mucormycosis) with fatal pulmonary dissemination.  Arch Dermatol. 1976;  112 509-512
  • 38 Bigby T D, Serota M L, Tierney Jr L M, Matthay M A. Clinical spectrum of pulmonary mucormycosis.  Chest. 1986;  89 435-439
  • 39 Pagano L, Ricci P, Nosari A et al.. Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Gimema Infection Program (Gruppo Italiano Malattie Ematologiche dell'Adulto).  Br J Haematol. 1995;  89 500-505
  • 40 Husari A W, Jensen W A, Kirsch C M et al.. Pulmonary mucormycosis presenting as an endobronchial lesion.  Chest. 1994;  106 1889-1891
  • 41 Everett E D, Pearson S, Rogers W. Rhizopus surgical wound infection with elasticized adhesive tape dressings.  Arch Surg. 1979;  114 738-739
  • 42 Adam R D, Hunter G, DiTomasso J, Comerci Jr G. Mucormycosis: emerging prominence of cutaneous infections.  Clin Infect Dis. 1994;  19 67-76
  • 43 Alsuwaida K. Primary cutaneous mucormycosis complicating the use of adhesive tape to secure the endotracheal tube.  Can J Anaesth. 2002;  49 880-882
  • 44 Bearer E A, Nelson P R, Chowers M Y, Davis C E. Cutaneous zygomycosis caused by Saksenaea vasiformis in a diabetic patient.  J Clin Microbiol. 1994;  32 1823-1824
  • 45 Scalise A, Barchiesi F, Viviani M A et al.. Infection due to Absidia corymbifera in a patient with a massive crush trauma of the foot.  J Infect. 1999;  38 191-192
  • 46 Nomura J, Ruskin J, Sahebi F, Kogut N, Falk P M. Mucormycosis of the vulva following bone marrow transplantation.  Bone Marrow Transplant. 1997;  19 859-860
  • 47 Newton W D, Cramer F S, Norwood S H. Necrotizing fasciitis from invasive Phycomycetes.  Crit Care Med. 1987;  15 331-332
  • 48 Lakshmi V, Rani T S, Sharma S et al.. Zygomycotic necrotizing fasciitis caused by Apophysomyces elegans .  J Clin Microbiol. 1993;  31 1368-1369
  • 49 Mooney J E, Wanger A. Mucormycosis of the gastrointestinal tract in children: report of a case and review of the literature.  Pediatr Infect Dis J. 1993;  12 872-876
  • 50 Carr E J, Scott P, Gradon J D. Fatal gastrointestinal mucormycosis that invaded the postoperative abdominal wall wound in an immunocompetent host.  Clin Infect Dis. 1999;  29 956-957
  • 51 Vadeboncoeur C, Walton J M, Raisen J et al.. Gastrointestinal mucormycosis causing an acute abdomen in the immunocompromised pediatric patient: three cases.  J Pediatr Surg. 1994;  29 1248-1249
  • 52 Knoop C, Antoine M, Vachiery J L et al.. Gastric perforation due to mucormycosis after heart-lung and heart transplantation.  Transplantation. 1998;  66 932-935
  • 53 Jackman Jr J D, Simonsen R L. The clinical manifestations of cardiac mucormycosis.  Chest. 1992;  101 1733-1736
  • 54 Virmani R, Connor D H, McAllister H A. Cardiac mucormycosis: a report of five patients and review of 14 previously reported cases.  Am J Clin Pathol. 1982;  78 42-47
  • 55 Fong K M, Seneviratne E M, McCormack J G. Mucor cerebral abscess associated with intravenous drug abuse.  Aust N Z J Med. 1990;  20 74-77
  • 56 Cook B A, White C B, Blaney S M, Bass J W. Survival after isolated cerebral mucormycosis.  Am J Pediatr Hematol Oncol. 1989;  11 330-333
  • 57 Santos J, Espigado P, Romero C et al.. Isolated renal mucormycosis in two AIDS patients.  Eur J Clin Microbiol Infect Dis. 1994;  13 430-432
  • 58 Eucker J, Sezer O, Graf B, Possinger K. Mucormycoses.  Mycoses. 2001;  44 253-260
  • 59 Murphy R A, Miller Jr W T. Pulmonary mucormycosis.  Semin Roentgenol. 1996;  31 83-87
  • 60 Glazer M, Nusair S, Breuer R et al.. The role of BAL in the diagnosis of pulmonary mucormycosis.  Chest. 2000;  117 279-282
  • 61 Al-Abbadi M A, Russo K, Wilkinson E J. Pulmonary mucormycosis diagnosed by bronchoalveolar lavage: a case report and review of the literature.  Pediatr Pulmonol. 1997;  23 222-225
  • 62 Chandler F W, Watts J C. Zygomycosis. In: Chandler FW, Watts JC Pathologic Diagnosis of Fungal Infections. Vol 1. Chicago; American Society of Clinical Pathologists 1987: 85-96
  • 63 Ribes J A, Vanover-Sams C, Baker D J. Zygomycetes in human disease.  Clin Microbiol Rev. 2000;  13 236-301
  • 64 Yeo S F, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections.  Clin Microbiol Rev. 2002;  15 465-484
  • 65 Parfrey N A. Improved diagnosis and prognosis of mucormycosis: a clinicopathologic study of 33 cases.  Medicine (Baltimore). 1986;  65 113-123
  • 66 Yohai R A, Bullock J D, Aziz A A, Markert R J. Survival factors in rhino-orbital-cerebral mucormycosis.  Surv Ophthalmol. 1994;  39 3-22
  • 67 Schmidt J M, Poublon R M. Rhinocerebral mycosis in immunocompromised patients: a case report and review of the literature.  Rhinology. 1998;  36 90-93
  • 68 Otcenasek M, Buchta V. In vitro susceptibility to 9 antifungal agents of 14 strains of Zygomycetes isolated from clinical specimens.  Mycopathologia. 1994;  128 135-137
  • 69 Dannaoui E, Mouton J W, Meis J F, Verweij P E. Efficacy of antifungal therapy in a nonneutropenic murine model of zygomycosis.  Antimicrob Agents Chemother. 2002;  46 1953-1959
  • 70 Gomez-Lopez A, Cuenca-Estrella M, Monzon A, Rodriguez-Tudela J L. In vitro susceptibility of clinical isolates of Zygomycota to amphotericin B, flucytosine, itraconazole and voriconazole.  J Antimicrob Chemother. 2001;  48 919-921
  • 71 Larkin J A, Montero J. Efficacy and safety of amphotericin B lipid complex for zygomycosis.  Infect Med. 2003;  20 201-206
  • 72 Wali Y A, al Lamki Z, al Kindi H et al.. Case report: successful outcome of invasive nasal sinus zygomycosis in a child with relapsed acute lymphoblastic leukaemia due to liposomal amphotericin B.  Mycoses. 2001;  44 195-199
  • 73 Dannaoui E, Afeltra J, Meis J F, Verweij P E. In vitro susceptibilities of zygomycetes to combinations of antimicrobial agents.  Antimicrob Agents Chemother. 2002;  46 2708-2711
  • 74 Walsh T J, Hiemenz J W, Seibel N L et al.. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases.  Clin Infect Dis. 1998;  26 1383-1396
  • 75 Linden P, Lee L, Walsh T J. Retrospective analysis of the dosage of amphotericin B lipid complex for the treatment of invasive fungal infections.  Pharmacotherapy. 1999;  19 1261-1268
  • 76 Ng T T, Denning D W. Liposomal amphotericin B (AmBisome) therapy in invasive fungal infections: evaluation of United Kingdom compassionate use data.  Arch Intern Med. 1995;  155 1093-1098
  • 77 Gebhard F, Chastagner P, Maillot D et al.. Favorable outcome of orbital nasal sinus mucormycosis complicating the induction treatment of acute lymphoblastic leukemia [in French].  Arch Pediatr. 1995;  2 47-51
  • 78 Parkyn T, McNinch A W, Riordan T, Mott M. Zygomycosis in relapsed acute leukaemia.  J Infect. 2000;  41 265-268
  • 79 Gaviria J M, Grohskopf L A, Barnes R, Root R K. Successful treatment of rhinocerebral zygomycosis: a combined-strategy approach.  Clin Infect Dis. 1999;  28 160-161
  • 80 Kfoury A G, Smith J C, Farhoud H H et al.. Adjuvant intrapleural amphotericin B therapy for pulmonary mucormycosis in a cardiac allograft recipient.  Clin Transplant. 1997;  11 608-612
  • 81 Sun Q N, Fothergill A W, McCarthy D I, Rinaldi M G, Graybill J R. In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes.  Antimicrob Agents Chemother. 2002;  46 1581-1582
  • 82 Sun Q N, Najvar L K, Bocanegra R, Loebenberg D, Graybill J R. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model.  Antimicrob Agents Chemother. 2002;  46 2310-2312
  • 83 Tobon A M, Arango M, Fernandez D, Restrepo A. Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy.  Clin Infect Dis. 2003;  36 1488-1491
  • 84 Greenberg N, Anstead G, Herbrecht R et al.. Posaconazole (POS) experience in the treatment of zygomycosis. Program and abstracts of the 43rd Annual ICAAC Chicago, Illinois; September 14-17, 2003
  • 85 Mazade M A, Margolin J F, Rossmann S N, Edwards M S. Survival from pulmonary infection with Cunninghamella bertholletiae: case report and review of the literature.  Pediatr Infect Dis J. 1998;  17 835-839
  • 86 McAdams H P, Rosado de Christenson M, Strollo D C, Patz Jr E F. Pulmonary mucormycosis: radiologic findings in 32 cases.  AJR Am J Roentgenol. 1997;  168 1541-1548
  • 87 Asai K, Suzuki K, Takahashi T et al.. Pulmonary resection with chest wall removal and reconstruction for invasive pulmonary mucormycosis during antileukemia chemotherapy.  Jpn J Thorac Cardiovasc Surg. 2003;  51 163-166
  • 88 Slavin M A, Kannan K, Buchanan M R, Sasadeusz J, Roberts A W. Successful allogeneic stem cell transplant after invasive pulmonary zygomycosis.  Leuk Lymphoma. 2002;  43 437-439
  • 89 Price J C, Stevens D L. Hyperbaric oxygen in the treatment of rhinocerebral mucormycosis.  Laryngoscope. 1980;  90(5 pt 1) 737-747
  • 90 Bentur Y, Shupak A, Ramon Y et al.. Hyperbaric oxygen therapy for cutaneous/soft-tissue zygomycosis complicating diabetes mellitus.  Plast Reconstr Surg. 1998;  102 822-824
  • 91 Ferguson B J, Mitchell T G, Moon R, Camporesi E M, Farmer J. Adjunctive hyperbaric oxygen for treatment of rhinocerebral mucormycosis.  Rev Infect Dis. 1988;  10 551-559
  • 92 Liles W C, Huang J E, van Burik J A, Bowden R A, Dale D C. Granulocyte colony-stimulating factor administered in vivo augments neutrophil-mediated activity against opportunistic fungal pathogens.  J Infect Dis. 1997;  175 1012-1015
  • 93 Brummer E, Maqbool A, Stevens D A. Protection of bronchoalveolar macrophages by granulocyte-macrophage colony-stimulating factor against dexamethasone suppression of fungicidal activity for Aspergillus fumigatus conidia.  Med Mycol. 2001;  39 509-515
  • 94 Ma B, Seymour J F, Januszewicz H, Slavin M A. Cure of pulmonary Rhizomucor pusillus infection in a patient with hairy-cell leukemia: role of liposomal amphotericin B and GM-CSF.  Leuk Lymphoma. 2001;  42 1393-1399
  • 95 Garcia-Diaz J B, Palau L, Pankey G A. Resolution of rhinocerebral zygomycosis associated with adjuvant administration of granulocyte-macrophage colony-stimulating factor.  Clin Infect Dis. 2001;  32 e145-e150
  • 96 Maury S, Leblanc T, Feuilhade M, Molina J M, Schaison G. Successful treatment of disseminated mucormycosis with liposomal amphotericin B and surgery in a child with leukemia.  Clin Infect Dis. 1998;  26 200-202
  • 97 Saltoglu N, Tasova Y, Zorludemir S, Dundar I H. Rhinocerebral zygomycosis treated with liposomal amphotericin B and surgery.  Mycoses. 1998;  41 45-49

Alison G FreifeldM.D. 

Infectious Diseases Section, Department of Medicine

985400 University of Nebraska Medical Center

Omaha, NE 68198-5400

Email: afreifeld@unmc.edu

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