Cryptococcus neoformans in organ transplant recipients

Impact of calcineurin-inhibitor agents on mortality

Nina Singh, Barbara D. Alexander, Olivier Lortholary, Françoise Dromer, Krishan L. Gupta, George T. John, Ramon Del Busto, Goran B. Klintmalm, Jyoti Somani, G. Marshall Lyon, Kenneth Pursell, Valentina Stosor, Patricia Muňoz, Ajit P. Limaye, Andre C. Kalil, Timothy L. Pruett, Julia Garcia-Diaz, Atul Humar, Sally Houston, Andrew A. House & 17 others Dannah Wray, Susan Orloff, Lorraine A. Dowdy, Robert A. Fisher, Joseph Heitman, Marilyn M. Wagener, Shahid Husain, Corinne Antoine, Barrou Benoît, Anne Elisabeth Heng, Christophe Legendre, Christian Michelet, Bénédicte Ponceau, Nacéra Ouali, Marc Stern, Theresa Sheppard, Marshall Lyon

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P = .048). The overall mortality rate at 90 days was 14% (16/111). The mortality rate was higher in patients with abnormal mental status (P = .023), renal failure at baseline (P = .028), fungemia (P = .006), and disseminated infection (P = .035) and was lower in those receiving a calcin eurin-inhibitor agent (P = .003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P = .008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P = .037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.

Original languageEnglish (US)
Pages (from-to)756-764
Number of pages9
JournalJournal of Infectious Diseases
Volume195
Issue number5
DOIs
StatePublished - Mar 1 2007

Fingerprint

Cryptococcus neoformans
Cryptococcosis
Transplants
Mortality
Infection
Renal Insufficiency
Fungemia
Immunosuppressive Agents
Multicenter Studies
Transplant Recipients
Calcineurin Inhibitors
Liver

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Singh, N., Alexander, B. D., Lortholary, O., Dromer, F., Gupta, K. L., John, G. T., ... Lyon, M. (2007). Cryptococcus neoformans in organ transplant recipients: Impact of calcineurin-inhibitor agents on mortality. Journal of Infectious Diseases, 195(5), 756-764. https://doi.org/10.1086/511438

Cryptococcus neoformans in organ transplant recipients : Impact of calcineurin-inhibitor agents on mortality. / Singh, Nina; Alexander, Barbara D.; Lortholary, Olivier; Dromer, Françoise; Gupta, Krishan L.; John, George T.; Del Busto, Ramon; Klintmalm, Goran B.; Somani, Jyoti; Lyon, G. Marshall; Pursell, Kenneth; Stosor, Valentina; Muňoz, Patricia; Limaye, Ajit P.; Kalil, Andre C.; Pruett, Timothy L.; Garcia-Diaz, Julia; Humar, Atul; Houston, Sally; House, Andrew A.; Wray, Dannah; Orloff, Susan; Dowdy, Lorraine A.; Fisher, Robert A.; Heitman, Joseph; Wagener, Marilyn M.; Husain, Shahid; Antoine, Corinne; Benoît, Barrou; Heng, Anne Elisabeth; Legendre, Christophe; Michelet, Christian; Ponceau, Bénédicte; Ouali, Nacéra; Stern, Marc; Sheppard, Theresa; Lyon, Marshall.

In: Journal of Infectious Diseases, Vol. 195, No. 5, 01.03.2007, p. 756-764.

Research output: Contribution to journalArticle

Singh, N, Alexander, BD, Lortholary, O, Dromer, F, Gupta, KL, John, GT, Del Busto, R, Klintmalm, GB, Somani, J, Lyon, GM, Pursell, K, Stosor, V, Muňoz, P, Limaye, AP, Kalil, AC, Pruett, TL, Garcia-Diaz, J, Humar, A, Houston, S, House, AA, Wray, D, Orloff, S, Dowdy, LA, Fisher, RA, Heitman, J, Wagener, MM, Husain, S, Antoine, C, Benoît, B, Heng, AE, Legendre, C, Michelet, C, Ponceau, B, Ouali, N, Stern, M, Sheppard, T & Lyon, M 2007, 'Cryptococcus neoformans in organ transplant recipients: Impact of calcineurin-inhibitor agents on mortality', Journal of Infectious Diseases, vol. 195, no. 5, pp. 756-764. https://doi.org/10.1086/511438
Singh, Nina ; Alexander, Barbara D. ; Lortholary, Olivier ; Dromer, Françoise ; Gupta, Krishan L. ; John, George T. ; Del Busto, Ramon ; Klintmalm, Goran B. ; Somani, Jyoti ; Lyon, G. Marshall ; Pursell, Kenneth ; Stosor, Valentina ; Muňoz, Patricia ; Limaye, Ajit P. ; Kalil, Andre C. ; Pruett, Timothy L. ; Garcia-Diaz, Julia ; Humar, Atul ; Houston, Sally ; House, Andrew A. ; Wray, Dannah ; Orloff, Susan ; Dowdy, Lorraine A. ; Fisher, Robert A. ; Heitman, Joseph ; Wagener, Marilyn M. ; Husain, Shahid ; Antoine, Corinne ; Benoît, Barrou ; Heng, Anne Elisabeth ; Legendre, Christophe ; Michelet, Christian ; Ponceau, Bénédicte ; Ouali, Nacéra ; Stern, Marc ; Sheppard, Theresa ; Lyon, Marshall. / Cryptococcus neoformans in organ transplant recipients : Impact of calcineurin-inhibitor agents on mortality. In: Journal of Infectious Diseases. 2007 ; Vol. 195, No. 5. pp. 756-764.
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abstract = "Variables influencing the risk of dissemination and outcome of Cryptococcus neoformans infection were assessed in 111 organ transplant recipients with cryptococcosis in a prospective, multicenter, international study. Sixty-one percent (68/111) of the patients had disseminated infection. The risk of disseminated cryptococcosis was significantly higher for liver transplant recipients (adjusted hazard ratio [HR], 6.65; P = .048). The overall mortality rate at 90 days was 14{\%} (16/111). The mortality rate was higher in patients with abnormal mental status (P = .023), renal failure at baseline (P = .028), fungemia (P = .006), and disseminated infection (P = .035) and was lower in those receiving a calcin eurin-inhibitor agent (P = .003). In a multivariable analysis, the receipt of a calcineurin-inhibitor agent was independently associated with a lower mortality (adjusted HR, 0.21; P = .008), and renal failure at baseline with a higher mortality rate (adjusted HR, 3.14; P = .037). Thus, outcome in transplant recipients with cryptococcosis appears to be influenced by the type of immunosuppressive agent employed. Additionally, discerning the basis for transplant type-specific differences in disease severity has implications relevant for yielding further insights into the pathogenesis of C. neoformans infection in transplant recipients.",
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AU - Singh, Nina

AU - Alexander, Barbara D.

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AU - Dromer, Françoise

AU - Gupta, Krishan L.

AU - John, George T.

AU - Del Busto, Ramon

AU - Klintmalm, Goran B.

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AU - Garcia-Diaz, Julia

AU - Humar, Atul

AU - Houston, Sally

AU - House, Andrew A.

AU - Wray, Dannah

AU - Orloff, Susan

AU - Dowdy, Lorraine A.

AU - Fisher, Robert A.

AU - Heitman, Joseph

AU - Wagener, Marilyn M.

AU - Husain, Shahid

AU - Antoine, Corinne

AU - Benoît, Barrou

AU - Heng, Anne Elisabeth

AU - Legendre, Christophe

AU - Michelet, Christian

AU - Ponceau, Bénédicte

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AU - Sheppard, Theresa

AU - Lyon, Marshall

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