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单纯的(1,3)-β-D-葡聚糖检测结果为阴性并不足以排除血液系统恶性肿瘤患者的肺炎诊断。

A Negative (1,3)-β-D-Glucan Result Alone Is Not Sufficient to Rule Out a Diagnosis of Pneumonia in Patients With Hematological Malignancies.

作者信息

Damiani Céline, Demey Baptiste, Pauc Cécile, Le Govic Yohann, Totet Anne

机构信息

Laboratoire de Parasitologie-Mycologie, Centre de Biologie Humaine, CHU Amiens-Picardie, Amiens, France.

Agents Infectieux, Résistance et Chimiothérapie (AGIR), UR 4294, Université de Picardie Jules Verne, Amiens, France.

出版信息

Front Microbiol. 2021 Aug 11;12:713265. doi: 10.3389/fmicb.2021.713265. eCollection 2021.


DOI:10.3389/fmicb.2021.713265
PMID:34456893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8386019/
Abstract

Serum (1,3)-β-D-glucan (BG) testing is increasingly being used in the diagnostic armamentarium for invasive fungal diseases. Given its high sensitivity, some studies suggest that a negative BG result contributes to rule out a diagnosis of pneumonia (PCP). However, recent reports described a suboptimal sensitivity in HIV-negative immunocompromised patients. In this study, we evaluated the performance of BG assay for PCP diagnosis in HIV-negative patients with diverse PCP risk factors. We also assessed the correlation between load in pulmonary samples and serum BG levels. We retrospectively included HIV-negative patients with microscopically proven PCP and for whom a BG result was available. We also enrolled patients colonized by as control group. Colonized patients were matched with PCP patients based on their underlying condition that exposed to PCP. Pulmonary fungal loads were determined by an in-house real-time PCR, and BG levels were measured by using the Fungitell® kit (Associates of Cape Cod, Inc.). Thirty-nine patients were included in each of the two groups. Thirty-four of 39 PCP patients and one of 39 colonized patient had a positive BG test, resulting in a sensitivity of 0.87 (95% CI: 0.73-0.94), a specificity of 0.97 (95% CI: 0.87-0.99), a positive predictive value of 0.97 (95% CI: 0.85-0.99), and a negative predictive value of 0.88 (95% CI: 0.75-0.95) for BG assay. Nonetheless, median BG level differed according to the underlying condition. Among the PCP group, the lowest median level of 211 pg/ml was observed in patients with hematological malignancy (HM) and differed significantly from that observed either in solid organ transplants (3,473 pg/ml) or in patients with autoimmune or inflammatory disorder (3,480 pg/ml). Indeed, the sensitivity of BG assay was estimated at 0.64 (95% CI: 0.35-0.85) in HM patients and was lower than the one observed in the whole PCP group. Furthermore, BG level and fungal burden correlated poorly among all PCP patients. BG is not a reliable biomarker for ruling out PCP in HIV-negative patients with HM. Interpretation of a negative BG result should take into account, but not be limited to, the underlying condition predisposing to PCP.

摘要

血清(1,3)-β-D-葡聚糖(BG)检测在侵袭性真菌病的诊断手段中应用越来越广泛。鉴于其高敏感性,一些研究表明BG检测结果为阴性有助于排除肺炎(PCP)的诊断。然而,最近的报告指出在HIV阴性的免疫功能低下患者中其敏感性欠佳。在本研究中,我们评估了BG检测在具有不同PCP危险因素的HIV阴性患者中对PCP诊断的性能。我们还评估了肺部样本中的负荷与血清BG水平之间的相关性。我们回顾性纳入了经显微镜证实为PCP且有BG检测结果的HIV阴性患者。我们还纳入了被定殖的患者作为对照组。根据暴露于PCP的基础疾病,将定殖患者与PCP患者进行匹配。通过内部实时PCR测定肺部真菌负荷,使用Fungitell®试剂盒(科德角联合公司)测量BG水平。两组各纳入39例患者。39例PCP患者中有34例BG检测呈阳性,39例定殖患者中有1例BG检测呈阳性,BG检测的敏感性为0.87(95%CI:0.73-0.94),特异性为0.97(95%CI:0.87-0.99),阳性预测值为0.97(95%CI:0.85-0.99),阴性预测值为0.88(95%CI:0.75-0.95)。尽管如此,BG的中位数水平因基础疾病而异。在PCP组中,血液系统恶性肿瘤(HM)患者的BG中位数水平最低,为211 pg/ml,与实体器官移植患者(3473 pg/ml)或自身免疫或炎症性疾病患者(3480 pg/ml)中观察到的水平有显著差异。实际上,HM患者中BG检测的敏感性估计为0.64(95%CI:0.35-0.85),低于整个PCP组中观察到的敏感性。此外,在所有PCP患者中,BG水平与真菌负荷的相关性较差。对于排除患有HM的HIV阴性患者的PCP,BG不是一个可靠的生物标志物。对BG检测结果为阴性的解读应考虑但不限于易患PCP的基础疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/5817afa5ce43/fmicb-12-713265-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/8d7e1f256acf/fmicb-12-713265-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/ee381a321921/fmicb-12-713265-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/403052176e61/fmicb-12-713265-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/5817afa5ce43/fmicb-12-713265-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/8d7e1f256acf/fmicb-12-713265-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/ee381a321921/fmicb-12-713265-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/403052176e61/fmicb-12-713265-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61dd/8386019/5817afa5ce43/fmicb-12-713265-g004.jpg

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本文引用的文献

[1]
Diagnostic accuracy of the 1,3-beta-D-glucan test and lactate dehydrogenase for pneumocystis pneumonia in non-HIV patients.

Sci Rep. 2021-4-29

[2]
Assessment of the Role of 1,3-β-d-Glucan Testing for the Diagnosis of Invasive Fungal Infections in Adults.

Clin Infect Dis. 2021-3-12

[3]
Pneumocystis jirovecii Disease: Basis for the Revised EORTC/MSGERC Invasive Fungal Disease Definitions in Individuals Without Human Immunodeficiency Virus.

Clin Infect Dis. 2021-3-12

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Pathogens. 2021-2-19

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Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease.

J Fungi (Basel). 2020-12-29

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Diagnostic evaluation of serum (1, 3)-β-d-glucan levels using the Fungitec G-Test MK kit for Pneumocystis jirovecii pneumonia (PCP) in non-HIV patients.

Med Mycol. 2020-12-28

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Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis-A Multicenter ECMM Excellence Center Study.

J Fungi (Basel). 2020-12-1

[8]
Clinical evaluation of two different (1,3)-ß-d-glucan assays for diagnosis of invasive fungal diseases: A retrospective cohort study.

Mycoses. 2021-2

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Serum (1,3)-Beta-d-Glucan has suboptimal performance for the diagnosis of Pneumocystis jirovecii pneumonia in cancer patients and correlates poorly with respiratory burden as measured by quantitative PCR.

J Infect. 2020-9

[10]
Epidemiology of Pneumonia and (Non-)use of Prophylaxis.

Front Cell Infect Microbiol. 2020-5-15

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