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(1-3)-beta-D-glucan guided early termination of antifungal therapy in ICU patients

(1-3)-β-D-葡聚糖指导 ICU 患者提前终止抗真菌治疗

基本信息

批准号：
400727961
负责人：
Privatdozent Dr. Jürgen Held
金额：
--
依托单位：
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2018
资助国家：
德国
起止时间：
2017-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/400727961?language=en
关键词：
beta glucan guided early termination

项目摘要

Background: Approximately 70 % of ICU patients receive antibiotics and as a consequence the extent of Candida colonization in these patients increases daily. With Candida spp. detected from various body sites the urge to start antifungal treatment in case of a clinical deterioration is high and up to 65 % of ICU patients receiving such therapy have no documented invasive fungal disease (IFD). However, unnecessary antifungal treatment is associated with potentially severe side effects, an increase in multiresistent Candida spp. and a significant financial burden for the health care system. (1-3)-beta-D-glucan (BDG) is a main cell wall component of various medically relevant fungi and can be detected in serum of patients with IFD. BDG has a high sensitivity and a negative predictive value of up to 99.9 % for the detection of IFD. In contrast, the specificity is only moderate and the positive predictive value is poor. In the past, multiple studies have used serum BDG measurement for screening of patients at risk of IFD or to initiate antifungal treatment in patients with suspected IFD. However, this approach has led to a significant overuse of antifungal drugs with potentially severe side effects for the patients. It is now recognized, that diagnostic strategies should utilize the high negative predictive value of BDG measurement to rule out IFD and to discontinue antifungal therapy in case of negative BDG results. Methods: We plan to conduct a prospective, randomized intervention study using the Fungitell assay for BDG measurement to guide an early termination of antifungal therapy in ICU patients. All patients with an antifungal therapy that was started in the ICU and without proven IFD are included in the study. The patients will be randomized to an intervention group and a control group. In both groups serum BDG will be determined on day 1 and 2 of antifungal therapy. If both measurements are negative the antifungal therapy will be discontinued in the intervention group but not in the control group. The decision when to stop the antifungal treatment in the control group is made at the discretion of the treating physician without knowledge of the BDG results. The patients will be followed-up for 28 days and clinical as well as microbiological data will be collected. The primary endpoint is antifungal drug usage in daily defined doses. Secondary endpoints are 28 day mortality, development of a proven IFD, side effects attributable to antifungal therapy, SOFA score in the ICU, length of stay in the ICU and length of hospitalization. Hypothesis: By using the negative predictive value of two consecutive negative BDG-values to discontinue antifungal therapy in patients without proven fungal infection we will be able to significantly reduce antifungal consumption without negative consequences for the patient.

背景：大约 70% 的 ICU 患者接受抗生素治疗，因此这些患者体内的念珠菌定植程度每天都在增加。与念珠菌属。从身体的各个部位检测到，在临床恶化的情况下开始抗真菌治疗的迫切性很高，接受这种治疗的 ICU 患者中高达 65% 的患者没有记录到侵袭性真菌病 (IFD)。然而，不必要的抗真菌治疗可能会带来潜在的严重副作用，即多重耐药念珠菌的增加。并对医疗保健系统造成沉重的经济负担。 (1-3)-β-D-葡聚糖（BDG）是多种医学相关真菌的主要细胞壁成分，可在 IFD 患者的血清中检测到。 BDG对于IFD的检测灵敏度高，阴性预测值高达99.9%。相比之下，特异性仅为中等，阳性预测价值较差。过去，多项研究使用血清 BDG 测量来筛查有 IFD 风险的患者或对疑似 IFD 的患者启动抗真菌治疗。然而，这种方法导致抗真菌药物的严重过度使用，对患者可能产生严重的副作用。现在人们认识到，诊断策略应利用 BDG 测量的高阴性预测值来排除 IFD，并在 BDG 结果阴性的情况下停止抗真菌治疗。方法：我们计划使用 Fungitell 测定法进行 BDG 测量进行前瞻性、随机干预研究，以指导 ICU 患者早期终止抗真菌治疗。所有在 ICU 开始接受抗真菌治疗且未证实 IFD 的患者均纳入本研究。患者将被随机分为干预组和对照组。两组的血清 BDG 将在抗真菌治疗的第 1 天和第 2 天测定。如果两项测量结果均为阴性，则干预组将停止抗真菌治疗，但对照组不会停止。对照组中何时停止抗真菌治疗的决定是由治疗医生在不知道 BDG 结果的情况下自行决定的。将对患者进行为期 28 天的随访，并收集临床和微生物学数据。主要终点是按每日规定剂量使用抗真菌药物。次要终点是 28 天死亡率、经证实的 IFD 的发展、抗真菌治疗引起的副作用、ICU 的 SOFA 评分、ICU 的住院时间和住院时间。假设：通过使用两个连续阴性 BDG 值的阴性预测值来停止未证实真菌感染的患者的抗真菌治疗，我们将能够显着减少抗真菌药物的消耗，而不会给患者带来负面后果。