Clinical Division of Intensive Care Medicine, UZ Leuven, Herestraat 49, 3000, Leuven, Belgium.
Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
Crit Care. 2019 Aug 2;23(1):270. doi: 10.1186/s13054-019-2549-8.
Invasive fungal infections (IFI) are difficult to diagnose, especially in critically ill patients. As the mannose receptor (MR) is shed from macrophage cell surfaces after exposure to fungi, we investigate whether its soluble serum form (sMR) can serve as a biomarker of IFI.
This is a secondary analysis of the multicentre randomised controlled trial (EPaNIC, n = 4640) that investigated the impact of initiating supplemental parenteral nutrition (PN) early during critical illness (Early-PN) as compared to withholding it in the first week of intensive care (Late-PN). Serum sMR concentrations were measured in three matched patient groups (proven/probable IFI, n = 82; bacterial infection, n = 80; non-infectious inflammation, n = 77) on the day of antimicrobial initiation or matched intensive care unit day and the five preceding days, as well as in matched healthy controls (n = 59). Independent determinants of sMR concentration were identified via multivariable linear regression. Serum sMR time profiles were analysed with repeated-measures ANOVA. Predictive properties were assessed via area under the receiver operating curve (aROC).
Serum sMR was higher in IFI patients than in all other groups (all p < 0.02), aROC to differentiate IFI from no IFI being 0.65 (p < 0.001). The ability of serum sMR to discriminate infectious from non-infectious inflammation was better with an aROC of 0.68 (p < 0.001). The sMR concentrations were already elevated up to 5 days before antimicrobial initiation and remained stable over time. Multivariable linear regression analysis showed that an infection or an IFI, higher severity of illness and sepsis upon admission were associated with higher sMR levels; urgent admission and Late-PN were independently associated with lower sMR concentrations.
Serum sMR concentrations were higher in critically ill patients with IFI than in those with a bacterial infection or with non-infectious inflammation. However, test properties were insufficient for diagnostic purposes.
侵袭性真菌感染（IFI）难以诊断，尤其是在重症患者中。由于甘露糖受体（MR）在巨噬细胞暴露于真菌后从细胞表面脱落，我们研究其可溶性血清形式（sMR）是否可作为 IFI 的生物标志物。
这是一项多中心随机对照试验（EPaNIC，n=4640）的二次分析，该试验研究了在重症监护的第一周开始补充肠外营养（Early-PN）与延迟（Late-PN）相比对早期开始补充肠外营养对重症患者的影响。在开始使用抗生素的当天或相匹配的重症监护病房日以及前五天，以及相匹配的健康对照组（n=59）中，测量三组匹配患者（IFI 的确诊/可能病例，n=82；细菌感染，n=80；非感染性炎症，n=77）的血清 sMR 浓度。通过多变量线性回归确定 sMR 浓度的独立决定因素。通过重复测量方差分析分析血清 sMR 时间曲线。通过接受者操作特征曲线（aROC）下面积评估预测特性。
IFI 患者的血清 sMR 高于所有其他组（均 p<0.02），区分 IFI 与非 IFI 的 aROC 为 0.65（p<0.001）。血清 sMR 区分感染性和非感染性炎症的能力更好，aROC 为 0.68（p<0.001）。在开始使用抗生素之前，sMR 浓度就已经升高，并且在整个过程中保持稳定。多变量线性回归分析显示，感染或 IFI、入院时更严重的疾病和脓毒症与更高的 sMR 水平相关；紧急入院和 Late-PN 与较低的 sMR 浓度独立相关。
与细菌感染或非感染性炎症患者相比，IFI 重症患者的血清 sMR 浓度更高。然而，该检测的诊断性能不足。
