Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients

Nina Singh, Drew J. Winston, Ajit P. Limaye, Shawn Pelletier, Nasia Safdar, Michele I Morris, Katherine Meneses, Ronald W. Busuttil, Marilyn M. Wagener, L. Joseph Wheat

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Abstract

Background. The utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain. Methods. As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs. Results. Overall, 46.4% of the patients at baseline had positiveGM(index ≥ 0.5) and 89.6%had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100%(12/12) of the patients with IFI had positive baseline BGand as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P <0.001). Conclusions. The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.

Original languageEnglish (US)
Pages (from-to)2543-2550
Number of pages8
JournalTransplantation
Volume99
Issue number12
DOIs
StatePublished - 2015

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Glucans
Aspergillosis
Liver
ROC Curve
Renal Replacement Therapy
Aspergillus
Invasive Fungal Infections
Transplant Recipients
galactomannan
Multivariate Analysis
Sensitivity and Specificity
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Transplantation

Cite this

Singh, N., Winston, D. J., Limaye, A. P., Pelletier, S., Safdar, N., Morris, M. I., ... Wheat, L. J. (2015). Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients. Transplantation, 99(12), 2543-2550. https://doi.org/10.1097/TP.0000000000000763

Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients. / Singh, Nina; Winston, Drew J.; Limaye, Ajit P.; Pelletier, Shawn; Safdar, Nasia; Morris, Michele I; Meneses, Katherine; Busuttil, Ronald W.; Wagener, Marilyn M.; Wheat, L. Joseph.

In: Transplantation, Vol. 99, No. 12, 2015, p. 2543-2550.

Research output: Contribution to journalArticle

Singh, N, Winston, DJ, Limaye, AP, Pelletier, S, Safdar, N, Morris, MI, Meneses, K, Busuttil, RW, Wagener, MM & Wheat, LJ 2015, 'Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients', Transplantation, vol. 99, no. 12, pp. 2543-2550. https://doi.org/10.1097/TP.0000000000000763
Singh, Nina ; Winston, Drew J. ; Limaye, Ajit P. ; Pelletier, Shawn ; Safdar, Nasia ; Morris, Michele I ; Meneses, Katherine ; Busuttil, Ronald W. ; Wagener, Marilyn M. ; Wheat, L. Joseph. / Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients. In: Transplantation. 2015 ; Vol. 99, No. 12. pp. 2543-2550.
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abstract = "Background. The utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain. Methods. As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs. Results. Overall, 46.4{\%} of the patients at baseline had positiveGM(index ≥ 0.5) and 89.6{\%}had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8{\%}. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5{\%} of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100{\%}(12/12) of the patients with IFI had positive baseline BGand as did 88.9{\%} (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P <0.001). Conclusions. The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.",
author = "Nina Singh and Winston, {Drew J.} and Limaye, {Ajit P.} and Shawn Pelletier and Nasia Safdar and Morris, {Michele I} and Katherine Meneses and Busuttil, {Ronald W.} and Wagener, {Marilyn M.} and Wheat, {L. Joseph}",
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T1 - Performance characteristics of galactomannan and β-d-glucan in high-risk liver transplant recipients

AU - Singh, Nina

AU - Winston, Drew J.

AU - Limaye, Ajit P.

AU - Pelletier, Shawn

AU - Safdar, Nasia

AU - Morris, Michele I

AU - Meneses, Katherine

AU - Busuttil, Ronald W.

AU - Wagener, Marilyn M.

AU - Wheat, L. Joseph

PY - 2015

Y1 - 2015

N2 - Background. The utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain. Methods. As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs. Results. Overall, 46.4% of the patients at baseline had positiveGM(index ≥ 0.5) and 89.6%had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100%(12/12) of the patients with IFI had positive baseline BGand as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P <0.001). Conclusions. The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.

AB - Background. The utility of Aspergillus galactomannan (GM) and β-D-glucan (BG) in liver transplant recipients remains uncertain. Methods. As part of a randomized, double-blind trial of antifungal prophylaxis in liver transplant recipients at risk for invasive fungal infections (IFIs), GM and BG were assessed in 199 patients at baseline (enrollment) and weekly thereafter for the duration of study drug. Receiver operating characteristic (ROC) analysis was used to evaluate the accuracy of these for the diagnosis of IFIs. Results. Overall, 46.4% of the patients at baseline had positiveGM(index ≥ 0.5) and 89.6%had BG of 80 pg/mL or greater with BG level of 500 pg/mL or greater in 31.8%. Patients with invasive aspergillosis (IA) (3/3) had positive GM at baseline as did 45.5% of those without IA (P = 0.098); the area under the ROC curve for the diagnosis of IA was 0.77 (fair test, ie, good sensitivity but poor specificity). Using BG cutoff of 80 pg/mL or higher, 100%(12/12) of the patients with IFI had positive baseline BGand as did 88.9% (160/180) of those without IFI (P = 0.618); the area under the ROC curve for predicting IFIs was 0.56 (poor test). In multivariate analyses, GM positivity was associated with study site (P = 0.041), and BG positivity with renal replacement therapy (P = 0.05) and study site (P = 0.01). The GM and BG levels declined over time; positivity at subsequent time points was lower in comparison with baseline (P <0.001). Conclusions. The GM and BG tests had significant center variability and limited accuracy for the diagnosis of IFIs in high-risk liver transplant recipients.

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