Siopi Maria, Karakatsanis Stamatis, Roumpakis Christoforos, Korantanis Konstantinos, Eldeik Elina, Sambatakou Helen, Sipsas Nikolaos V, Tsirigotis Panagiotis, Pagoni Maria, Meletiadis Joseph
Clinical Microbiology Laboratory, "Attikon" University General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Unit of Bone Marrow Transplantation, Department of Hematology and Lymphoma, "Evangelismos" General Hospital, 10676 Athens, Greece.
J Fungi (Basel). 2021 Mar 13;7(3):211. doi: 10.3390/jof7030211.
As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-β-D-glucan (BDG) and DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens ( = 240) from 93 adult hematology patients with probable ( = 8), possible ( = 25) and no ( = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0% for GM (X = 55, < 0.001), 62%/46%/35% for BDG (X = 2.5, = 0.29), 62%/33%/27% for PCR (X = 3.9, = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X = 31, < 0.001), 50%/8%/22% for BDG + PCR (X = 6.5, = 0.038) and 38%/4%/0% for GM + BDG + PCR (X = 21, < 0.001). Higher agreement (76%) and negative correlation (r = -0.47, = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45-55% and 90-92% when biomarkers assessed alone and increased to 75-90% and 93-97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11-0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA.
由于侵袭性曲霉病（IA）的传统微生物学诊断依据难以获得，血清真菌生物标志物是重要的辅助诊断工具。我们对血液系统恶性肿瘤高危患者的半乳甘露聚糖（GM）、1,3-β-D-葡聚糖（BDG）和DNA（PCR）的阳性率及动力学特征进行了研究。回顾性分析了93例成年血液科患者（可能患有IA的8例、可能患有IA的25例、未患IA的60例）连续血清标本（n = 240）的GM、BDG和PCR数据。评估了每种真菌生物标志物单独及联合使用时的阳性率和敏感度/特异度/阳性/阴性预测值（NPV）。对这三种标志物进行了直接比较，并与各种生化、人口统计学和患者特征进行了关联分析。对于可能患有/可能患有/未患IA的患者，GM的阳性率分别为88%/8%/0%（χ² = 55，P < 0.001），BDG的阳性率分别为62%/46%/35%（χ² = 2.5，P = 0.29），PCR的阳性率分别为62%/33%/27%（χ² = 3.9，P = 0.15），GM + BDG和GM + PCR的阳性率分别为50%/4%/0%（χ² = 31，P < 0.001），BDG + PCR的阳性率分别为50%/8%/22%（χ² = 6.5，P = 0.038），GM + BDG + PCR的阳性率分别为38%/4%/0%（χ² = 21，P < 0.001）。GM指数与PCR Ct值之间具有较高的一致性（76%）和负相关性（r = -0.47，P = 0.0017）。单独评估生物标志物时，敏感度和NPV分别为45 - 55%和90 - 92%，联合使用时分别提高到75 - 90%和93 - 97%。GM、PCR和BDG结果与肾/肝功能标志物之间存在弱的显著相关性（r = 0.11 - 0.57），大多数GM阳性和PCR阳性样本分别在临床评估的第一周和第二周发现，而BDG阳性样本稍后发现。这三种生物标志物的阳性率、时间特征和性能各不相同，提倡将GM与PCR联合用于IA的早期诊断，而联合生物标志物的高NPV有助于排除IA。
