Skip to main content

Cryptococcus Infections in Transplant Recipients

  • Chapter
  • First Online:
Principles and Practice of Transplant Infectious Diseases

Abstract

Cryptococcosis is the third most common invasive fungal infection among solid organ transplant recipients but has been reported very rarely in hematopoietic stem cell transplant recipients. Pulmonary cryptococcal disease is the most common clinical presentation, and the central nervous system involvement is the most common extrapulmonary site. Diagnosis is confirmed by isolation of the fungus from culture samples and measuring cryptococcal antigen in various body fluids including serum and CSF; histologic evidence of dimorphic fungi in tissue samples may provide a clue to the etiology and in most instances is not required to confirm the diagnosis. Depending on disease severity and extent of infection, treatment consists of lipid formulations of amphotericin B plus flucytosine, and/or fluconazole. Reduction in immunosuppression should also be attempted in transplant recipients with acute cryptococcal infection. However, attempts in rapid reduction of immune suppression may theoretically place patients at risk for cryptococcal immune reconstitution inflammatory syndrome. In this chapter, a comprehensive review of cryptococcal disease is presented in context of patients undergoing solid organ and hematopoietic stem cell transplantation.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kwon-Chung KJ, Bennett JE. Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol. 1984;120(1):123–30.

    Article  CAS  PubMed  Google Scholar 

  2. Harris JR, Lockhart SR, Debess E, et al. Cryptococcus gattii in the United States: clinical aspects of infection with an emerging pathogen. Clin Infect Dis. 2011;53(12):1188–95.

    Article  CAS  PubMed  Google Scholar 

  3. Banerjee P, Haider M, Trehan V, et al. Cryptococcus laurentii fungemia. Indian J Med Microbiol. 2013;31(1):75–7.

    Article  CAS  PubMed  Google Scholar 

  4. Shankar EM, Kumarasamy N, Bella D, et al. Pneumonia and pleural effusion due to Cryptococcus laurentii in a clinically proven case of AIDS. Can Respir J. 2006;13(5):275–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cleveland KO, Gelfand MS, Rao V. Posaconazole as successful treatment for fungemia due to Cryptococcus albidus in a liver transplant recipient. QJM. 2013;106(4):361–2.

    Article  CAS  PubMed  Google Scholar 

  6. Emmons CW. Saprophytic sources of Cryptococcus neoformans associated with the pigeon (Columba livia). Am J Hyg. 1955;62(3):227–32.

    CAS  PubMed  Google Scholar 

  7. Lazera MS, Pires FD, Camillo-Coura L, et al. Natural habitat of Cryptococcus neoformans var. neoformans in decaying wood forming hollows in living trees. J Med Vet Mycol. 1996;34(2):127–31.

    Article  CAS  PubMed  Google Scholar 

  8. Ellis DH, Pfeiffer TJ. Natural habitat of Cryptococcus neoformans var. gattii. J Clin Microbiol. 1990;28(7):1642–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kidd SE, Hagen F, Tscharke RL, et al. A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada). Proc Natl Acad Sci U S A. 2004;101(49):17258–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Baddley JW, Forrest GN. Cryptococcosis in solid organ transplantation. Am J Transplant. 2013;13(Suppl 4):242–9.

    Article  CAS  PubMed  Google Scholar 

  11. Brizendine KD, Baddley JW, Pappas PG. Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PLoS One. 2013;8(3):e60431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sun HY, Wagener MM, Singh N. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends. Clin Infect Dis. 2009;48(11):1566–76.

    Article  PubMed  Google Scholar 

  13. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50(8):1091–100.

    Article  PubMed  Google Scholar 

  14. Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50(8):1101–11.

    Article  PubMed  Google Scholar 

  15. Arthurs SK, Eid AJ, Deziel PJ, et al. The impact of invasive fungal diseases on survival after lung transplantation. Clin Transpl. 2010;24(3):341–8.

    Article  Google Scholar 

  16. Garcia-Hermoso D, Janbon G, Dromer F. Epidemiological evidence for dormant Cryptococcus neoformans infection. J Clin Microbiol. 1999;37(10):3204–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Saha DC, Goldman DL, Shao X, et al. Serologic evidence for reactivation of cryptococcosis in solid-organ transplant recipients. Clin Vaccine Immunol. 2007;14(12):1550–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kapoor A, Flechner SM, O'Malley K, Paolone D, File TM Jr, Cutrona AF. Cryptococcal meningitis in renal transplant patients associated with environmental exposure. Transpl Infect Dis. 1999;1(3):213–7.

    Article  CAS  PubMed  Google Scholar 

  19. Neuville S, Dromer F, Morin O, Dupont B, Ronin O, Lortholary O. Primary cutaneous cryptococcosis: a distinct clinical entity. Clin Infect Dis. 2003;36(3):337–47.

    Article  PubMed  Google Scholar 

  20. Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis. 2001;7(3):375–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Singh N, Alexander BD, Lortholary O, et al. Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality. J Infect Dis. 2007;195(5):756–64.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Baddley JW, Schain DC, Gupte AA, et al. Transmission of Cryptococcus neoformans by Organ Transplantation. Clin Infect Dis. 2011;52(4):e94–8.

    Article  PubMed  Google Scholar 

  23. Ooi BS, Chen BT, Lim CH, Khoo OT, Chan DT. Survival of a patient transplanted with a kidney infected with Cryptococcus neoformans. Transplantation. 1971;11(4):428–9.

    Article  CAS  PubMed  Google Scholar 

  24. Kanj SS, Welty-Wolf K, Madden J, et al. Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature. Medicine (Baltimore). 1996;75(3):142–56.

    Article  CAS  Google Scholar 

  25. Singh N. How I treat cryptococcosis in organ transplant recipients. Transplantation. 2012;93(1):17–21.

    Article  PubMed  Google Scholar 

  26. Chuang YM, Ho YC, Chang HT, Yu CJ, Yang PC, Hsueh PR. Disseminated cryptococcosis in HIV-uninfected patients. Eur J Clin Microbiol Infect Dis. 2008;27(4):307–10.

    Article  PubMed  Google Scholar 

  27. Singh N, Husain S, De Vera M, Gayowski T, Cacciarelli TV. Cryptococcus neoformans infection in patients with cirrhosis, including liver transplant candidates. Medicine (Baltimore). 2004;83(3):188–92.

    Article  Google Scholar 

  28. Silveira FP, Husain S, Kwak EJ, et al. Cryptococcosis in liver and kidney transplant recipients receiving anti-thymocyte globulin or alemtuzumab. Transpl Infect Dis. 2007;9(1):22–7.

    Article  CAS  PubMed  Google Scholar 

  29. 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(2):204–12.

    Article  CAS  PubMed  Google Scholar 

  30. Baddley JW, Perfect JR, Oster RA, et al. Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease. Eur J Clin Microbiol Infect Dis. 2008;27(10):937–43.

    Article  CAS  PubMed  Google Scholar 

  31. Pappas PG, Perfect JR, Cloud GA, et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis. 2001;33(5):690–9.

    Article  CAS  PubMed  Google Scholar 

  32. Singh N, Gayowski T, Wagener MM, Marino IR. Clinical spectrum of invasive cryptococcosis in liver transplant recipients receiving tacrolimus. Clin Transpl. 1997;11(1):66–70.

    CAS  Google Scholar 

  33. Mueller NJ, Fishman JA. Asymptomatic pulmonary cryptococcosis in solid organ transplantation: report of four cases and review of the literature. Transpl Infect Dis. 2003;5(3):140–3.

    Article  CAS  PubMed  Google Scholar 

  34. Paterson DL, Singh N, Gayowski T, Marino IR. Pulmonary nodules in liver transplant recipients. Medicine (Baltimore). 1998;77(1):50–8.

    Article  CAS  Google Scholar 

  35. Singh N, Alexander BD, Lortholary O, et al. Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis. 2008;46(2):e12–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Jabbour N, Reyes J, Kusne S, Martin M, Fung J. Cryptococcal meningitis after liver transplantation. Transplantation. 1996;61(1):146–9.

    Article  CAS  PubMed  Google Scholar 

  37. Singh N, Lortholary O, Dromer F, et al. Central nervous system cryptococcosis in solid organ transplant recipients: clinical relevance of abnormal neuroimaging findings. Transplantation. 2008;86(5):647–51.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Baer S, Baddley JW, Gnann JW, Pappas PG. Cryptococcal disease presenting as necrotizing cellulitis in transplant recipients. Transpl Infect Dis. 2009;11(4):353–8.

    Article  CAS  PubMed  Google Scholar 

  39. Bruno KM, Farhoomand L, Libman BS, Pappas CN, Landry FJ. Cryptococcal arthritis, tendinitis, tenosynovitis, and carpal tunnel syndrome: report of a case and review of the literature. Arthritis Rheum. 2002;47(1):104–8.

    Article  PubMed  Google Scholar 

  40. Siddiqui TJ, Zamani T, Parada JP. Primary cryptococcal prostatitis and correlation with serum prostate specific antigen in a renal transplant recipient. J Infect. 2005;51(3):e153–7.

    Article  PubMed  Google Scholar 

  41. Okun E, Butler WT. Ophthalmologic complications of cryptococcal meningitis. Arch Ophthalmol. 1964;71:52–7.

    Article  CAS  PubMed  Google Scholar 

  42. Rex JH, Larsen RA, Dismukes WE, Cloud GA, Bennett JE. Catastrophic visual loss due to Cryptococcus neoformans meningitis. Medicine (Baltimore). 1993;72(4):207–24.

    Article  CAS  Google Scholar 

  43. Denning DW, Armstrong RW, Fishman M, Stevens DA. Endophthalmitis in a patient with disseminated cryptococcosis and AIDS who was treated with itraconazole. Rev Infect Dis. 1991;13(6):1126–30.

    Article  CAS  PubMed  Google Scholar 

  44. Mocan H, Murphy AV, Beattie TJ, McAllister TA. Fungal peritonitis in children on continuous ambulatory peritoneal dialysis. Scott Med J. 1989;34(4):494–6.

    Article  CAS  PubMed  Google Scholar 

  45. Kauffman CA, Bergman AG, Severance PJ, McClatchey KD. Detection of cryptococcal antigen. Comparison of two latex agglutination tests. Am J Clin Pathol. 1981;75(1):106–9.

    Article  CAS  PubMed  Google Scholar 

  46. Singh N, Dromer F, Perfect JR, Lortholary O. Cryptococcosis in solid organ transplant recipients: current state of the science. Clin Infect Dis. 2008;47(10):1321–7.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Wu G, Vilchez RA, Eidelman B, Fung J, Kormos R, Kusne S. Cryptococcal meningitis: an analysis among 5,521 consecutive organ transplant recipients. Transpl Infect Dis. 2002;4(4):183–8.

    Article  CAS  PubMed  Google Scholar 

  48. Singh N, Forrest G. Cryptococcosis in solid organ transplant recipients. Am J Transplant. 2009;9 Suppl 4:S192–8.

    Article  CAS  PubMed  Google Scholar 

  49. Gazzoni AF, Severo CB, Salles EF, Severo LC. Histopathology, serology and cultures in the diagnosis of cryptococcosis. Rev Inst Med Trop Sao Paulo. 2009;51(5):255–9.

    Article  PubMed  Google Scholar 

  50. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010;50(3):291–322.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Thompson GR 3rd, Wiederhold NP, Fothergill AW, Vallor AC, Wickes BL, Patterson TF. Antifungal susceptibilities among different serotypes of Cryptococcus gattii and Cryptococcus neoformans. Antimicrob Agents Chemother. 2009;53(1):309–11.

    Article  CAS  PubMed  Google Scholar 

  52. Thompson GR 3rd, Fothergill AW, Wiederhold NP, Vallor AC, Wickes BL, Patterson TF. Evaluation of Etest method for determining isavuconazole MICs against Cryptococcus gattii and Cryptococcus neoformans. Antimicrob Agents Chemother. 2008;52(8):2959–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Brandt ME, Pfaller MA, Hajjeh RA, et al. Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates in the United States: 1992 to 1994 and 1996 to 1998. Antimicrob Agents Chemother. 2001;45(11):3065–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sun HY, Alexander BD, Lortholary O, et al. Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis. Clin Infect Dis. 2009;49(11):1721–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dromer F, Mathoulin-Pelissier S, Launay O, Lortholary O. Determinants of disease presentation and outcome during cryptococcosis: the CryptoA/D study. PLoS Med. 2007;4(2):e21.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Dromer F, Bernede-Bauduin C, Guillemot D, Lortgercllholary O. Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PLoS One. 2008;3(8):e2870.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Graybill JR, Sobel J, Saag M, et al. Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups. Clin Infect Dis. 2000;30(1):47–54.

    Article  CAS  PubMed  Google Scholar 

  58. Singh N, Lortholary O, Alexander BD, et al. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients. Clin Infect Dis. 2005;40(12):1756–61.

    Article  CAS  PubMed  Google Scholar 

  59. Singh N, Lortholary O, Alexander BD, et al. Allograft loss in renal transplant recipients with cryptococcus neoformans associated immune reconstitution syndrome. Transplantation. 2005;80(8):1131–3.

    Article  PubMed  Google Scholar 

  60. Charlier C, Dromer F, Leveque C, et al. Cryptococcal neuroradiological lesions correlate with severity during cryptococcal meningoencephalitis in HIV-positive patients in the HAART era. PLoS One. 2008;3(4):e1950.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Kontoyiannis DP, Lewis RE, Alexander BD, et al. Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob Agents Chemother. 2008;52(2):735–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Raymund R. Razonable .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Razonable, R.R., Chong, P.P. (2019). Cryptococcus Infections in Transplant Recipients. In: Safdar, A. (eds) Principles and Practice of Transplant Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9034-4_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9034-4_35

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-9032-0

  • Online ISBN: 978-1-4939-9034-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics