ICM:G试验指导的脓毒症患者抗真菌治疗

Abstract

Purpose: To investigate whether (1 → 3)‐β‐d‐Glucan (BDG)‐guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI).

目的：研究 (1→3)-β‐d‐葡聚糖 (BDG) 指导是否缩短了抗真菌治疗的时间，从而降低了侵袭性念珠菌感染 (ICI) 高危的败血症患者的死亡率。

Methods: Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received anti‐ fungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empiri‐ cal antifungal therapy was discouraged in both groups. The primary endpoint was 28‐day‐mortality.

方法：2016年9月至2019年9月在18家重症监护室开展的多中心、随机、对照试验，入组了ICI高风险的成人脓毒症患者。对照组患者在培养结果驱动下接受靶向抗真菌治疗。除靶向治疗外，如果在前两个研究日采集的两份连续 BDG 样本中至少一份≥80 pg/mL，则 BDG 组患者接受抗真菌药。两组均不鼓励经验性抗真菌治疗。主要终点为28天死亡率。

Results: 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG‐group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80–1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0–2.2] days in the BDG group and 4.4 (IQR 2.0–9.1, p < 0.01) days in the control group.

结果：入选339例患者。入组后前 96 h 内诊断 ICI 48 例 (14.2%)。在 BDG 组中，48.8%(84/172) 的患者在入组后的前 96 h 内接受抗真菌药，对照组中为6%(10/167) 的患者。BDG 组172例患者中的58例 (33.7%) 和对照组167例患者中的51例 (30.5%) 在第28天前死亡（相对风险1.10；95%置信区间，0.80-1.51；p = 0.53）。BDG 组抗真菌治疗的中位时间为1.1[四分位距 (IQR)1.0-2.2] 天，对照组为4.4(IQR 2.0-9.1，p < 0.01) 天。

Conclusions: Serum BDG guided antifungal treatment did not improve 28‐day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG‐guidance in a more selected at‐risk population.

结论：血清 BDG 指导的抗真菌治疗未改善具有 IC 风险因素的脓毒症患者28天死亡率，但 IC 发生率意外降低。本研究无法评论 BDG 指南在更多选择的风险人群中的潜在获益。