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Zygomycosis: An emerging fungal infection with new options for management

Abstract

Zygomycosis occurs primarily in immunosuppressed patients and those with diabetes mellitus. Diabetes remains the most common risk factor; however, zygomycosis has increased among transplant recipients and patients with hematologic malignancy. Treatment or prophylaxis with voriconazole seems to be associated with the development of zygomycosis among severely immunosuppressed patients in these latter risk groups. Rhino-orbital-cerebral zygomycosis is the most common manifestation in patients with diabetes mellitus, but transplant recipients and patients with hematologic malignancy are more likely to develop pulmonary infection. Zygomycosis remains difficult to treat and requires a multifaceted approach involving elimination of predisposing factors, surgical debridement, and antifungal therapy. Lipid formulations of amphotericin B are the treatments of choice. The use of posaconazole has been successful in salvage trials but should not be used as first-line therapy until an effective intravenous formulation is available.

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References

  1. Ribes JA, Vanover-Sams CL, Baker DJ: Zygomycetes in human disease. Clin Microbiol Rev 2000, 13:236–301.

    PubMed  Article  CAS  Google Scholar 

  2. Spellberg B, Edwards J, Ibrahim A: Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 2005, 18:556–569.

    PubMed  Article  CAS  Google Scholar 

  3. Gomez-Lopez A, Cuenca-Estrella M, Monzon A, Rodriquez-Tudela JL: In vitro susceptibility of clinical isolates of Zygomycota to amphotericin B, flucytosine, itraconazole, and voriconazole. J Antimicrob Chemother 2001, 48:919–921.

    PubMed  Article  CAS  Google Scholar 

  4. 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, 46:1581–1582.

    PubMed  Article  CAS  Google Scholar 

  5. Torres-Narbona M, Guiniea J, Martinez-Alarcon J, et al.: In vitro activities of amphotericin B, caspofungin, itraconazole, posaconazole, and voriconazole against 45 clinical isolates of zygomycetes: comparison of CLSI M38-A, Sensititre Yeast One, and the E test. Antimicrob Agents Chemother 2007, 51:1126–1129.

    PubMed  Article  CAS  Google Scholar 

  6. Andresen D, Donaldson A, Choo L, et al.: Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. Lancet 2005, 365:876–878.

    PubMed  Article  Google Scholar 

  7. Oliver MR, Van Voorhis WC, Boeckh M, et al.: Hepatic mucormycosis in a bone marrow transplant recipient who ingested naturopathic medicine. Clin Infect Dis 1996, 22:521–524.

    PubMed  CAS  Google Scholar 

  8. Roden MM, Zaoutis TE, Buchanan WL, et al.: Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis 2005, 41:634–653.

    PubMed  Article  Google Scholar 

  9. Baddley JW, Stroud TP, Salzman D, Pappas PG: Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001, 32:1319–1324.

    PubMed  Article  CAS  Google Scholar 

  10. Kontoyiannis DP, Wessel VC, Bodey GP, Rolston KV: Zygomycosis in the 1990s in a tertiary-care cancer center. Clin Infect Dis 2000, 30:851–856.

    PubMed  Article  CAS  Google Scholar 

  11. Almyroudis NG, Sutton DA, Linden P, et al.: Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature. Am J Transplant 2006, 6:2365–2374.

    PubMed  Article  CAS  Google Scholar 

  12. Kontoyiannis DG: Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis 2007, 44:1089–1090.

    PubMed  Article  Google Scholar 

  13. Chakrabarti A, Das A, Mandal J, et al.: The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med Mycol 2006, 44:335–342.

    PubMed  Article  Google Scholar 

  14. Boelaert JR, van Roost GF, Verqauwe PL, et al.: The role of desferrioxamine in dialysis-associated myucormycosis: report of three cases and review of the literature. Clin Nephrol 1988, 29:261–266.

    PubMed  CAS  Google Scholar 

  15. Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, et al.: Invasive zygomycosis in hematopoietic stem-cell transplant patients receiving voriconazole prophylaxis. Clin Infect Dis 2004, 39:584–587.

    PubMed  Article  Google Scholar 

  16. Marty FM, Cosimi LA, Baden LR: Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem cell transplants. N Engl J Med 2004, 350:950–952.

    PubMed  Article  CAS  Google Scholar 

  17. Imhof A, Balajee SA, Fredricks DN, et al.: Breakthrough fungal infections in stem cell transplant patients receiving voriconazole. Clin Infect Dis 2004, 39:743–746.

    PubMed  Article  Google Scholar 

  18. Vigouroux S, Morin O, Moreau P, et al.: Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematological disease: attention required. Clin Infect Dis 2005, 40:e35–e37.

    PubMed  Article  Google Scholar 

  19. Kobayashi K, Kami M, Murashige N, et al.: Breakthrough zygomycosis during voriconazole treatment for invasive aspergillosis. Haematologica 2004, 89:ECR42.

    PubMed  Google Scholar 

  20. Oren I: Breakthrough zygomycosis during empirical voriconazole therapy in febrile patients with neutropenia. Clin Infect Dis 2005, 40:770–771.

    PubMed  Article  Google Scholar 

  21. Trifilio SM, Bennett CL, Yarnold PR, et al.: Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant 2007, 39:425–429.

    PubMed  Article  CAS  Google Scholar 

  22. 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, 191:1350–1360.

    PubMed  Article  Google Scholar 

  23. Prabhu RM, Patel R: Mucormycosis and entomophthoramycosis: a review of the clinical manifestations, diagnosis and treatment. Clin Microbiol Infect 2004, 10(Suppl 1):31–47.

    PubMed  Article  Google Scholar 

  24. Hopkins RJ, Rothman M, Fiore A, Goldblum SE: Cerebral mucormycosis associated with intravenous drug use: three case reports and review. Clin Infect Dis 1994, 19:1133–1137.

    PubMed  CAS  Google Scholar 

  25. Chamilos G, Marom EM, Lewis RE, et al.: Predictors of pulmonary zygomycosis versus pulmonary aspergillosis in patients with cancer. Clin Infect Dis 2005, 41:60–66.

    PubMed  Article  Google Scholar 

  26. Adams RD, Hunter G, DiTomasso J, Comerci G: Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 1994, 19:67–76.

    Google Scholar 

  27. Agha FP, Lee HH, Boland CR, Bradley SF: Mucormycoma of the colon: early diagnosis and successful management. Am J Roentgenol 1985, 145:739–741.

    CAS  Google Scholar 

  28. Padmanabhan S, Battiwalla M, Hahn T, et al.: Two cases of hepatic zygomycosis in allogeneic stem cell transplant recipients and review of literature. Transpl Infect Dis 2007, 9:148–152.

    PubMed  Article  CAS  Google Scholar 

  29. Rinaldi MG: Zygomycosis. Infect Dis Clin N Am 1989, 3:19–41.

    CAS  Google Scholar 

  30. Kontoyiannis DP, Chamilos G, Lewis RE, Tarrand JJ: Increased culture recovery of zygomycetes under physiologic temperatuire conditions [abstract #279]. Presented at the 43rd Annual Meeting of the Infectious Diseases Society of America. San Francisco, CA; October 6–9, 2005.

  31. Schwarz P, Bretagne S, Gantier JC, et al.: Molecular identification of Zygomycetes from culture and experimentally infected tissues. J Clin Microbiol 2006, 44:340–349.

    PubMed  Article  CAS  Google Scholar 

  32. Perfect JR: Treatment of non-Aspergillus moulds in immunocompromised patients, with amphotericin B lipid complex. Clin Infect Dis 2005, 40:s401–s408.

    PubMed  Article  CAS  Google Scholar 

  33. Herbrecht R, Letscher-Bru V, Bowden RA, et al.: Treatment of 21 cases of invasive mucormycosis with amphotericin B colloidal dispersion. Eur J Clin Microbiol Infect Dis 2001, 20:460–466.

    PubMed  Article  CAS  Google Scholar 

  34. Forrest GN, Mankes K: Outcomes of invasive zygomycosis infections in renal transplant recipients. Transpl Infect Dis 2007, 9:161–164.

    PubMed  Article  CAS  Google Scholar 

  35. Torres HA, Hachem RY, Chemaly RF, et al.: Posaconazole: a broad-spectrum triazole antifungal. Lancet Infect Dis 2005, 5:775–785.

    PubMed  Article  CAS  Google Scholar 

  36. Greenberg RN, Mullane K, van Burik JA, et al.: Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 2006, 50:126–133.

    PubMed  Article  CAS  Google Scholar 

  37. Tobon AM, 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.

    PubMed  Article  Google Scholar 

  38. van Burik JA, Hare RS, Solomon HF, et al.: Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis 2006, 42:e61–e65.

    PubMed  Article  Google Scholar 

  39. Sansone-Parsons A, Krishna G, Calzetta A, et al.: Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother 2006, 50:1881–1883.

    PubMed  Article  CAS  Google Scholar 

  40. Ullmann AJ, Cornely OA, Burchardt A, et al.: Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006, 50:658–666.

    PubMed  Article  CAS  Google Scholar 

  41. Dannaoui E, Afeltra J, Meis JF, et al.: In vitro susceptibilities of zygomycetes to combinations of antimicrobial agents. Antimicrob Agents Chemother 2002, 46:2708–2711.

    PubMed  Article  CAS  Google Scholar 

  42. Voitl P, Scheibenpflug C, Weber T, et al.: Combined antifungal treatment of visceral mucormycosis with caspofungin and liposomal amphotericin B. Eur J Clin Microbiol Infect Dis 2002, 21:632–634.

    PubMed  Article  CAS  Google Scholar 

  43. Spellberg B, Fu Y, Edwards JE, Ibrahim AS: Combination therapy with amphotericin B lipid complex and caspofungin acetate of disseminated zygomycosis in diabetic ketoacidotic mice. Antimicrob Agents Chemother 2005, 49:830–832.

    PubMed  Article  CAS  Google Scholar 

  44. Reed C, Ibrahim A, Edwards JE Jr, et al.: Deferasirox, an iron chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob Agents Chemother 2006, 50:3968–3969.

    PubMed  Article  Google Scholar 

  45. 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, 15:866–869.

    PubMed  Article  CAS  Google Scholar 

  46. Garcia-Diaz JB, Palau L, Pankey GA: Resolution of rhinocerebral zygomycosis associated with adjuvant administration of granulocyte-macrophage colony-stimulating factor. Clin Infect Dis 2001, 32:e145–e150.

    PubMed  Article  CAS  Google Scholar 

  47. Ferguson BJ, Mitchell TG, Moon R, et al.: Adjunctive hyperbaric oxygen for treatment of rhinocerebral mucormycosis. Rev Infect Dis 1988, 10:551–559.

    PubMed  CAS  Google Scholar 

  48. John BV, Chamilos G, Kontoyiannis DP: Hyperbaric oxygen as an adjunctive treatment for zygomycosis. Clin Microbiol Infect 2005, 11:515–517.

    PubMed  Article  CAS  Google Scholar 

  49. Ibrahim AS, Edwards JE Jr, Fu Y, et al.: Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother 2006, 58:1070–1073.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Carol A. Kauffman.

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Kauffman, C.A., Malani, A.N. Zygomycosis: An emerging fungal infection with new options for management. Curr Infect Dis Rep 9, 435–440 (2007). https://doi.org/10.1007/s11908-007-0066-4

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Keywords

  • Voriconazole
  • Clin Infect
  • Invasive Aspergillosis
  • Antimicrob Agent
  • Posaconazole