Skip to main content

Advertisement

Log in

Prophylaxis of invasive mycoses in solid organ transplantation

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Solid organ transplantation is emerging as a lifesaving procedure for increasing numbers of patients, and invasive fungal infections are a significant cause of mortality and morbidity for patients undergoing such procedures. Risks for developing these infections are continuing to evolve, leading to shifts in the epidemiology of invasive mycoses occurring after transplantation. Targeting preventive efforts to select solid organ transplantation groups at highest risk for invasive fungal infections is critical to optimizing prophylaxis strategies. The epidemiology of posttransplantation fungal infections, antifungal drug interactions and side effects, and new diagnostic capabilities should be considered when choosing an approach to antifungal prophylaxis for this population.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Paya CV: Fungal infections in solid-organ transplantation. Clin Infect Dis 1993, 16:677–688.

    CAS  PubMed  Google Scholar 

  2. Abbott KC, Hypolite I, Poropatich RK, et al.: Hospitalizations for fungal infections after renal transplantation in the United States. Transpl Infect Dis 2001, 3:203–211.

    Article  CAS  PubMed  Google Scholar 

  3. Singh N, Avery RK, Munoz P, et al.: Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clin Infect Dis 2003, 36:46–52.

    Article  PubMed  Google Scholar 

  4. Martin-Davila P, Fortun J, Lopez-Velez R, et al.: Transmission of tropical and geographically restricted infections during solid-organ transplantation. Clin Microbiol Rev 2008, 21:60–96.

    Article  CAS  PubMed  Google Scholar 

  5. Raviv Y, Kramer MR, Amital A, et al.: Outbreak of aspergillosis infections among lung transplant recipients. Transpl Int 2007, 20:135–140.

    Article  PubMed  Google Scholar 

  6. Stelzmueller I, Lass-Floerl C, Geltner C, et al.: Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients. Transpl Int 2008, 21:534–546.

    Article  PubMed  Google Scholar 

  7. Gavalda J, Len O, San JR, et al.: Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study. Clin Infect Dis 2005, 41:52–59.

    Article  CAS  PubMed  Google Scholar 

  8. Chang FY, Singh N, Gayowski T, et al.: Thrombocytopenia in liver transplant recipients: predictors, impact on fungal infections, and role of endogenous thrombopoietin. Transplantation 2000, 69:70–75.

    Article  CAS  PubMed  Google Scholar 

  9. Zaas AK, Liao G, Chien JW, et al.: Plasminogen alleles influence susceptibility to invasive aspergillosis. PLoS Genet 2008, 4:e1000101.

    Article  PubMed  Google Scholar 

  10. George MJ, Snydman DR, Werner BG, et al.: The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med 1997, 103:106–113.

    Article  CAS  PubMed  Google Scholar 

  11. Wagner JA, Ross H, Hunt S, et al.: Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation. Transplantation 1995, 60:1473–1477.

    Article  CAS  PubMed  Google Scholar 

  12. Kalil AC, Levitsky J, Lyden E, et al.: Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med 2005, 143:870–880.

    PubMed  Google Scholar 

  13. Issa NC, Fishman JA: Infectious complications of antilymphocyte therapies in solid organ transplantation. Clin Infect Dis 2009, 48:772–786.

    Article  CAS  PubMed  Google Scholar 

  14. Mueller NJ: New immunosuppressive strategies and the risk of infection. Transpl Infect Dis 2008, 10:379–384.

    Article  CAS  PubMed  Google Scholar 

  15. Peleg AY, Husain S, Kwak EJ, et al.: Opportunistic infections in 547 organ transplant recipients receiving alemtuzumab, a humanized monoclonal CD-52 antibody. Clin Infect Dis 2007, 44:204–212.

    Article  CAS  PubMed  Google Scholar 

  16. Tan HP, Donaldson J, Basu A, et al.: Two hundred living donor kidney transplantations under alemtuzumab induction and tacrolimus monotherapy: 3-year follow-up. Am J Transplant 2009, 9:355–366.

    Article  CAS  PubMed  Google Scholar 

  17. Hadley S, Samore MH, Lewis WD, et al.: Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression. Transplantation 1995, 59:851–859.

    Article  CAS  PubMed  Google Scholar 

  18. Collins LA, Samore MH, Roberts MS, et al.: Risk factors for invasive fungal infections complicating orthotopic liver transplantation. J Infect Dis 1994, 170:644–652.

    CAS  PubMed  Google Scholar 

  19. Pappas PG, Andes D, Schuster M, et al.: Invasive fungal infections in low-risk liver transplant recipients: a multicenter prospective observational study. Am J Transplant 2006, 6:386–391.

    Article  CAS  PubMed  Google Scholar 

  20. Hadley S, Huckabee C, Pappas PG, et al.: Outcomes of antifungal prophylaxis in high-risk liver transplant recipients. Transpl Infect Dis 2009, 11:40–48.

    Article  CAS  PubMed  Google Scholar 

  21. Osawa M, Ito Y, Hirai T, et al.: Risk factors for invasive aspergillosis in living donor liver transplant recipients. Liver Transpl 2007, 13:566–570.

    Article  PubMed  Google Scholar 

  22. Singh N: Antifungal prophylaxis for solid organ transplant recipients: seeking clarity amidst controversy. Clin Infect Dis 2000, 31:545–553.

    Article  CAS  PubMed  Google Scholar 

  23. Silveira FP, Kwak EJ, Paterson DL, et al.: Post-transplant colonization with non-Aspergillus molds and risk of development of invasive fungal disease in lung transplant recipients. J Heart Lung Transplant 2008, 27:850–855.

    Article  PubMed  Google Scholar 

  24. Kowalski R, Post D, Schneider MC, et al.: Immune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient management. Clin Transplant 2003, 17:77–88.

    Article  PubMed  Google Scholar 

  25. Husain S, Raza K, Pilewski JM, et al.: Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection. Transplantation 2009, 87:1852–1857.

    Article  CAS  PubMed  Google Scholar 

  26. Munoz P, Rodriguez C, Bouza E, et al.: Risk factors of invasive aspergillosis after heart transplantation: protective role of oral itraconazole prophylaxis. Am J Transplant 2004, 4:636–643.

    Article  CAS  PubMed  Google Scholar 

  27. O’Neill JM, Schutze GE, Heulitt MJ, et al.: Nosocomial infections during extracorporeal membrane oxygenation. Intensive Care Med 2001, 27:1247–1253.

    Article  PubMed  Google Scholar 

  28. Albano L, Bretagne S, Mamzer-Bruneel MF, et al.: Evidence that graft-site candidiasis after kidney transplantation is acquired during organ recovery: a multicenter study in France. Clin Infect Dis 2009, 48:194–202.

    Article  PubMed  Google Scholar 

  29. Benedetti E, Gruessner AC, Troppmann C, et al.: Intra-abdominal fungal infections after pancreatic transplantation: incidence, treatment, and outcome. J Am Coll Surg 1996, 183:307–316.

    CAS  PubMed  Google Scholar 

  30. Alexander BD, Schell WA, Miller JL, et al.: Candida glabrata fungemia in transplant patients receiving voriconazole after fluconazole. Transplantation 2005, 80:868–871.

    Article  PubMed  Google Scholar 

  31. Kung N, Fisher N, Gunson B, et al.: Fluconazole prophylaxis for high-risk liver transplant recipients. Lancet 1995, 345:1234–1235.

    Article  CAS  PubMed  Google Scholar 

  32. Kontoyiannis DP: Why prior fluconazole use is associated with an increased risk of invasive mold infections in immunosuppressed hosts: an alternative hypothesis. Clin Infect Dis 2002, 34:1281–1283.

    Article  PubMed  Google Scholar 

  33. Sharpe MD, Ghent C, Grant D, et al.: Efficacy and safety of itraconazole prophylaxis for fungal infections after orthotopic liver transplantation: a prospective, randomized, double-blind study. Transplantation 2003, 76:977–983.

    Article  CAS  PubMed  Google Scholar 

  34. Winston DJ, Busuttil RW: Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients. Transplantation 2002, 74:688–695.

    Article  CAS  PubMed  Google Scholar 

  35. Shitrit D, Ollech JE, Ollech A, et al.: Itraconazole prophylaxis in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction. J Heart Lung Transplant 2005, 24:2148–2152.

    Article  PubMed  Google Scholar 

  36. Patterson TF, Peters J, Levine SM, et al.: Systemic availability of itraconazole in lung transplantation. Antimicrob Agents Chemother 1996, 40:2217–2220.

    CAS  PubMed  Google Scholar 

  37. VFend IV, tablets, oral suspension [package insert]. New York: Pfizer, Inc.; 2008.

  38. Husain S, Paterson DL, Studer S, et al.: Voriconazole prophylaxis in lung transplant recipients. Am J Transplant 2006, 6:3008–3016.

    Article  CAS  PubMed  Google Scholar 

  39. Boussaud V, Daudet N, Billaud EM, et al.: Neuromuscular painful disorders: a rare side effect of voriconazole in lung transplant patients under tacrolimus. J Heart Lung Transplant 2008, 27:229–232.

    Article  CAS  PubMed  Google Scholar 

  40. Noxafil (posaconazole) oral suspension [package insert]. Kenilworth, NJ: Schering-Plough Corp.; 2006.

  41. Alexander BD, Perfect JR, Daly JS, et al.: Posaconazole as salvage therapy in patients with invasive fungal infections after solid organ transplant. Transplantation 2008, 86:791–796.

    Article  CAS  PubMed  Google Scholar 

  42. Krishna G, Moton A, Ma L, et al.: Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 2009, 53:958–966.

    Article  CAS  PubMed  Google Scholar 

  43. Ullmann AJ, Lipton JH, Vesole DH, et al.: Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med 2007, 356:335–347.

    Article  CAS  PubMed  Google Scholar 

  44. Cornely OA, Maertens J, Winston DJ, et al.: Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007, 356:348–359.

    Article  CAS  PubMed  Google Scholar 

  45. Arathoon EG: Clinical efficacy of echinocandin antifungals. Curr Opin Infect Dis 2001, 14:685–691.

    CAS  PubMed  Google Scholar 

  46. Van Burik J, Ratanatharathorn V, Stepan D, et al.: Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 2004, 39:1407–1416.

    Article  PubMed  Google Scholar 

  47. Tollemar J, Hockerstedt K, Ericzon BG, et al.: Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study. Transplantation 1995, 59:45–50.

    Article  CAS  PubMed  Google Scholar 

  48. Lorf T, Braun F, Ruchel R, et al.: Systemic mycoses during prophylactical use of liposomal amphotericin B (Ambisome) after liver transplantation. Mycoses 1999, 42:47–53.

    Article  CAS  PubMed  Google Scholar 

  49. Castroagudin JF, Ponton C, Bustamante M, et al.: Prospective interventional study to evaluate the efficacy and safety of liposomal amphotericin B as prophylaxis of fungal infections in high-risk liver transplant recipients. Transplant Proc 2005, 37:3965–3967.

    Article  CAS  PubMed  Google Scholar 

  50. Singh N, Paterson DL, Gayowski T, et al.: Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy. Transplantation 2001, 71:910–913.

    Article  CAS  PubMed  Google Scholar 

  51. Reichenspurner H, Gamberg P, Nitschke M, et al.: Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis. Transplantation Proc 1997, 29:627–628.

    Article  CAS  Google Scholar 

  52. Drew RH, Dodds AE, Benjamin DK, et al.: Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation 2004, 77:232–237.

    Article  CAS  PubMed  Google Scholar 

  53. Cruciani M, Mengoli C, Malena M, et al.: Antifungal prophylaxis in liver transplant patients: a systematic review and meta-analysis. Liver Transpl 2006, 12:850–858.

    Article  PubMed  Google Scholar 

  54. Playford EG, Webster AC, Sorrell TC, et al.: Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients. Eur J Clin Microbiol Infect Dis 2006, 25:549–561.

    Article  CAS  PubMed  Google Scholar 

  55. Fungal infections. Am J Transplant 2004, 4(Suppl 10):110–134.

  56. Pappas PG, Kauffman CA, Andes D, et al.: Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009, 48:503–535.

    Article  CAS  PubMed  Google Scholar 

  57. Husain S, Zaldonis D, Kusne S, et al.: Variation in antifungal prophylaxis strategies in lung transplantation. Transpl Infect Dis 2006, 8:213–218.

    Article  CAS  PubMed  Google Scholar 

  58. Kwak EJ, Husain S, Obman A, et al.: Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay for diagnosis of invasive aspergillosis in liver transplant recipients. J Clin Microbiol 2004, 42:435–438.

    Article  PubMed  Google Scholar 

  59. Husain S, Kwak EJ, Obman A, et al.: Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant 2004, 4:796–802.

    Article  PubMed  Google Scholar 

  60. Pfeiffer CD, Fine JP, Safdar N: Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006, 42:1417–1427.

    Article  CAS  PubMed  Google Scholar 

  61. Singh N, Wagener MM, Cacciarelli TV, et al.: Antifungal management practices in liver transplant recipients. Am J Transplant 2008, 8:426–431.

    CAS  PubMed  Google Scholar 

  62. Akamatsu N, Sugawara Y, Kaneko J, et al.: Preemptive treatment of fungal infection based on plasma (1 → 3) beta-D-glucan levels after liver transplantation. Infection 2007, 35:346–351.

    Article  CAS  PubMed  Google Scholar 

  63. Lumbreras C, Cuervas-Mons V, Jara P, et al.: Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation. J Infect Dis 1996, 174:583–588.

    CAS  PubMed  Google Scholar 

  64. Palmer SM, Drew RH, Whitehouse JD, et al.: Safety of aerosolized amphotericin B lipid complex in lung transplant recipients. Transplantation 2001, 72:545–548.

    Article  CAS  PubMed  Google Scholar 

  65. Winston DJ, Pakrasi A, Busuttil RW: Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999, 131:729–737.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Barbara D. Alexander.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Radack, K.P., Alexander, B.D. Prophylaxis of invasive mycoses in solid organ transplantation. Curr Infect Dis Rep 11, 427–434 (2009). https://doi.org/10.1007/s11908-009-0062-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-009-0062-y

Keywords

Navigation