Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis

Hsin Yun Sun, Barbara D. Alexander, Olivier Lortholary, Francoise Dromer, Graeme N. Forrest, G. Marshall Lyon, Jyoti Somani, Krishan L. Gupta, Ramon Del Busto, Timothy L. Pruett, Costi D. Sifri, Ajit P. Limaye, George T. John, Goran B. Klintmalm, Kenneth Pursell, Valentina Stosor, Michelle I. Morris, Lorraine A. Dowdy, Patricia Munoz, Andre C. KalilJulia Garcia-Diaz, Susan Orloff, Andrew A. House, Sally Houston, Dannah Wray, Shirish Huprikar, Leonard B. Johnson, Atul Humar, Raymund R. Razonable, Shahid Husain, Nina Singh

Research output: Contribution to journalArticle

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Abstract

Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline ( P=.94). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (Pp.034), renal failure at baseline (P=.016), and fungemia (P=.003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P=.007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P=.349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P=.047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P= .004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; Pp.008). Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

Original languageEnglish (US)
Pages (from-to)1721-1728
Number of pages8
JournalClinical Infectious Diseases
Volume49
Issue number11
DOIs
StatePublished - Dec 2009

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Cryptococcosis
Amphotericin B
Central Nervous System
Transplants
Lipids
Mortality
Fungemia
Renal Insufficiency
Odds Ratio
Confidence Intervals
Polyenes
Flucytosine
Transplant Recipients
Multicenter Studies
Logistic Models
Regression Analysis
deoxycholate drug combination amphotericin B

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

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Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis. / Sun, Hsin Yun; Alexander, Barbara D.; Lortholary, Olivier; Dromer, Francoise; Forrest, Graeme N.; Lyon, G. Marshall; Somani, Jyoti; Gupta, Krishan L.; Del Busto, Ramon; Pruett, Timothy L.; Sifri, Costi D.; Limaye, Ajit P.; John, George T.; Klintmalm, Goran B.; Pursell, Kenneth; Stosor, Valentina; Morris, Michelle I.; Dowdy, Lorraine A.; Munoz, Patricia; Kalil, Andre C.; Garcia-Diaz, Julia; Orloff, Susan; House, Andrew A.; Houston, Sally; Wray, Dannah; Huprikar, Shirish; Johnson, Leonard B.; Humar, Atul; Razonable, Raymund R.; Husain, Shahid; Singh, Nina.

In: Clinical Infectious Diseases, Vol. 49, No. 11, 12.2009, p. 1721-1728.

Research output: Contribution to journalArticle

Sun, HY, Alexander, BD, Lortholary, O, Dromer, F, Forrest, GN, Lyon, GM, Somani, J, Gupta, KL, Del Busto, R, Pruett, TL, Sifri, CD, Limaye, AP, John, GT, Klintmalm, GB, Pursell, K, Stosor, V, Morris, MI, Dowdy, LA, Munoz, P, Kalil, AC, Garcia-Diaz, J, Orloff, S, House, AA, Houston, S, Wray, D, Huprikar, S, Johnson, LB, Humar, A, Razonable, RR, Husain, S & Singh, N 2009, 'Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis', Clinical Infectious Diseases, vol. 49, no. 11, pp. 1721-1728. https://doi.org/10.1086/647948
Sun, Hsin Yun ; Alexander, Barbara D. ; Lortholary, Olivier ; Dromer, Francoise ; Forrest, Graeme N. ; Lyon, G. Marshall ; Somani, Jyoti ; Gupta, Krishan L. ; Del Busto, Ramon ; Pruett, Timothy L. ; Sifri, Costi D. ; Limaye, Ajit P. ; John, George T. ; Klintmalm, Goran B. ; Pursell, Kenneth ; Stosor, Valentina ; Morris, Michelle I. ; Dowdy, Lorraine A. ; Munoz, Patricia ; Kalil, Andre C. ; Garcia-Diaz, Julia ; Orloff, Susan ; House, Andrew A. ; Houston, Sally ; Wray, Dannah ; Huprikar, Shirish ; Johnson, Leonard B. ; Humar, Atul ; Razonable, Raymund R. ; Husain, Shahid ; Singh, Nina. / Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis. In: Clinical Infectious Diseases. 2009 ; Vol. 49, No. 11. pp. 1721-1728.
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title = "Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis",
abstract = "Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3{\%}) received lipid formulations of amphotericin B and 20 (26.7{\%}) received AmBd. Similar proportions of patients in both groups had renal failure at baseline ( P=.94). Overall, mortality at 90 days was 10.9{\%} in the group that received lipid formulations of amphotericin B and 40.0{\%} in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (Pp.034), renal failure at baseline (P=.016), and fungemia (P=.003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P=.007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P=.349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95{\%} confidence interval [CI], 1.02-20.80; P=.047) and fungemia (OR, 10.66; 95{\%} CI, 2.08-54.55; P= .004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95{\%} CI, 0.02-0.57; Pp.008). Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.",
author = "Sun, {Hsin Yun} and Alexander, {Barbara D.} and Olivier Lortholary and Francoise Dromer and Forrest, {Graeme N.} and Lyon, {G. Marshall} and Jyoti Somani and Gupta, {Krishan L.} and {Del Busto}, Ramon and Pruett, {Timothy L.} and Sifri, {Costi D.} and Limaye, {Ajit P.} and John, {George T.} and Klintmalm, {Goran B.} and Kenneth Pursell and Valentina Stosor and Morris, {Michelle I.} and Dowdy, {Lorraine A.} and Patricia Munoz and Kalil, {Andre C.} and Julia Garcia-Diaz and Susan Orloff and House, {Andrew A.} and Sally Houston and Dannah Wray and Shirish Huprikar and Johnson, {Leonard B.} and Atul Humar and Razonable, {Raymund R.} and Shahid Husain and Nina Singh",
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T1 - Lipid formulations of amphotericin B significantly improve outcome in solid organ transplant recipients with central nervous system cryptococcosis

AU - Sun, Hsin Yun

AU - Alexander, Barbara D.

AU - Lortholary, Olivier

AU - Dromer, Francoise

AU - Forrest, Graeme N.

AU - Lyon, G. Marshall

AU - Somani, Jyoti

AU - Gupta, Krishan L.

AU - Del Busto, Ramon

AU - Pruett, Timothy L.

AU - Sifri, Costi D.

AU - Limaye, Ajit P.

AU - John, George T.

AU - Klintmalm, Goran B.

AU - Pursell, Kenneth

AU - Stosor, Valentina

AU - Morris, Michelle I.

AU - Dowdy, Lorraine A.

AU - Munoz, Patricia

AU - Kalil, Andre C.

AU - Garcia-Diaz, Julia

AU - Orloff, Susan

AU - House, Andrew A.

AU - Houston, Sally

AU - Wray, Dannah

AU - Huprikar, Shirish

AU - Johnson, Leonard B.

AU - Humar, Atul

AU - Razonable, Raymund R.

AU - Husain, Shahid

AU - Singh, Nina

PY - 2009/12

Y1 - 2009/12

N2 - Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline ( P=.94). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (Pp.034), renal failure at baseline (P=.016), and fungemia (P=.003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P=.007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P=.349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P=.047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P= .004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; Pp.008). Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

AB - Background: Whether outcome of central nervous system (CNS) cryptococcosis in solid organ transplant recipients treated with lipid formulations of amphotericin B is different from the outcome of the condition treated with amphotericin B deoxycholate (AmBd) is not known. Methods: We performed a multicenter study involving a cohort comprising consecutive solid organ transplant recipients with CNS cryptococcosis. Results: Of 75 patients treated with polyenes as induction regimens, 55 (73.3%) received lipid formulations of amphotericin B and 20 (26.7%) received AmBd. Similar proportions of patients in both groups had renal failure at baseline ( P=.94). Overall, mortality at 90 days was 10.9% in the group that received lipid formulations of amphotericin B and 40.0% in the group that received AmBd. In univariate analysis, nonreceipt of calcineurin inhibitors (Pp.034), renal failure at baseline (P=.016), and fungemia (P=.003) were significantly associated with mortality. Compared with AmBd, lipid formulations of amphotericin B were associated with a lower mortality (P=.007). Mortality did not differ between patients receiving lipid formulations of amphotericin B with or without flucytosine (P=.349). In stepwise logistic regression analysis, renal failure at baseline (odds ratio [OR], 4.61; 95% confidence interval [CI], 1.02-20.80; P=.047) and fungemia (OR, 10.66; 95% CI, 2.08-54.55; P= .004) were associated with an increased mortality, whereas lipid formulations of amphotericin B were associated with a lower mortality (OR, 0.11; 95% CI, 0.02-0.57; Pp.008). Conclusions: Lipid formulations of amphotericin B were independently associated with better outcome and may be considered as the first-line treatment for CNS cryptococcosis in these patients.

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