TY - JOUR
T1 - Correlation between circulating fungal biomarkers and clinical outcome in invasive aspergillosis
AU - Neofytos, Dionysios
AU - Railkar, Radha
AU - Mullane, Kathleen M.
AU - Fredricks, David N.
AU - Granwehr, Bruno
AU - Marr, Kieren A.
AU - Almyroudis, Nikolaos G.
AU - Kontoyiannis, Dimitrios P.
AU - Maertens, Johan
AU - Fox, Rebecca
AU - Douglas, Cameron
AU - Iannone, Robert
AU - Kauh, Eunkyung
AU - Shire, Norah
N1 - Funding Information:
R. Railkar, R. Fox, C. Douglas, R. Iannone, E. Kauh, and N. Shire are current or former employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, which provided funding towards this study. D. Neofytos, D. Fredricks, B. Granwehr and N. Almyroudis report grant from Merck & Co., Inc. K. Mullane reports grant from Merck & Co., Inc., outside the submitted work. K. Marr reports grant from Astellas, Merck & Co., Inc., and Pfizer, and received personal fees from Astellas, Merck, and Pfizer, outside the submitted work. K. Marr reports a US patent: Lateral Flow Device for Diagnosing Microbial Infections, US2013/0017561. D. Neofytos reports grants from Pfizer and personal fees from Roche and Astellas, outside the submitted work. D. Kontoyiannis reports grants from Merck & Co., Inc. and Pfizer; he received personal fees from Pfizer, Gilead, and Schering-Plough, outside the submitted work. J. Maertens reports no conflict of interest. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015 Neofytos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/6/24
Y1 - 2015/6/24
N2 - Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GMand BDG levels and GMoptical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2%(25/47) and 65.9%(27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05;GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2%(41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01;GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.
AB - Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA). We examined whether early changes in serum galactomannan (GM) and/or β-D-glucan (BDG) can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GMand BDG levels and GMoptical density indices (GMI) were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2%(25/47) and 65.9%(27/41) had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03) and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02). Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05;GMI, P = 0.03) and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01). Overall survival rates at 6 weeks and 12 weeks were 87.2%(41/47) and 79.1% (34/43), respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01;GM, P = 0.03) and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007). Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.
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U2 - 10.1371/journal.pone.0129022
DO - 10.1371/journal.pone.0129022
M3 - Article
C2 - 26107507
AN - SCOPUS:84939217461
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 6
M1 - e129022
ER -