TY - JOUR
T1 - Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents
AU - Fisher, Brian T.
AU - Boge, Craig L.K.
AU - Xiao, Rui
AU - Shuster, Sydney
AU - Chin-Quee, Dawn
AU - Allen, John
AU - Shaheen, Shareef
AU - Hayden, Randall
AU - Suganda, Sri
AU - Zaoutis, Theoklis E.
AU - Chang, Yeh Chung
AU - Yin, Dwight E.
AU - Huppler, Anna R.
AU - Danziger-Isakov, Lara
AU - Muller, William J.
AU - Roilides, Emmanuel
AU - Romero, José
AU - Sue, Paul K.
AU - Berman, David
AU - Wattier, Rachel L.
AU - Halasa, Natasha
AU - Pong, Alice
AU - Maron, Gabriela
AU - Soler-Palacin, Pere
AU - Hutto, Susan C.
AU - Gonzalez, Blanca E.
AU - Salvatore, Christine M.
AU - Rajan, Sujatha
AU - Green, Michael
AU - Doby Knackstedt, Elizabeth
AU - Hauger, Sarmistha B.
AU - Steinbach, William J.
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2022/7/15
Y1 - 2022/7/15
N2 - Background: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. Results: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%-97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). Conclusions: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. Clinical Trials Registration: NCT02220790.
AB - Background: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. Results: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%-97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). Conclusions: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. Clinical Trials Registration: NCT02220790.
KW - Pediatrics
KW - biomarkers
KW - invasive candidiasis
UR - http://www.scopus.com/inward/record.url?scp=85132121704&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132121704&partnerID=8YFLogxK
U2 - 10.1093/cid/ciab928
DO - 10.1093/cid/ciab928
M3 - Article
C2 - 35134165
AN - SCOPUS:85132121704
SN - 1058-4838
VL - 75
SP - 248
EP - 259
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 2
ER -