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侵袭性肺曲霉病患者的临床特征及生存结局评估。

Evaluation of the clinical characteristics and survival outcomes of invasive pulmonary aspergillosis patients.

作者信息

Feng Qiangsheng, Ha Xiaoqin, Song Yuejuan

机构信息

Department of Clinical Laboratory, The 940th Hospital of Joint Logistics Support Force of People's Liberation Army, Lanzhou, China.

出版信息

Front Microbiol. 2025 May 1;16:1587227. doi: 10.3389/fmicb.2025.1587227. eCollection 2025.

DOI:10.3389/fmicb.2025.1587227
PMID:40376458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12078237/
Abstract

BACKGROUND

Invasive pulmonary aspergillosis (IPA) is a severe infectious disease caused by spp. It is associated with high mortality, particularly in immunocompromised patients, as well as in those with COVID-19 pneumonia or critically ill individuals in intensive care units (ICUs). Accurate clinical diagnosis remains a significant challenge, often resulting in missed diagnoses.

METHODS

This study evaluated IPA inpatients diagnosed through mycological evidence and clinical criteria over 12 months. Inclusion criteria required at least one positive mycological result, including a positive culture from bronchoalveolar lavage fluid (BALF) or high-quality sputum, or a positive galactomannan antigen (GM) test.

RESULTS

A total of 216 patients were diagnosed with IPA, with a mortality rate of 68.5%. Hematologic malignancies were the primary underlying condition in 33.8% of cases. Voriconazole or posaconazole was used in 45% (98/216) of patients overall, but only 26% (32/121) of non-hematologic malignancy patients received these treatments. The 28-day survival rate for patients treated with Voriconazole/Posaconazole was 0.776 ± 0.038, compared to 0.421 ± 0.043 for untreated patients. Median survival was 130 days (95% CI, 35.3-224.7) for treated patients vs. 20 days (95% CI, 15.8-24.2) for untreated patients ( < 0.001). Biomarkers for IPA diagnosis demonstrated high diagnostic value, with area under the curve (AUC) values for GM, G, PCT, IL-6, WBC, NEU%, and D-dimer of 0.953, 0.983, 1.000, 0.999, 0.961, 0.996, and 1.000, respectively. GM levels >0.5 pg/ml had a positive predictive value of 52.9% (27/51), while positive mycological culture had a predictive value of 46.5% (33/71). Multivariable regression analysis identified several significant factors associated with in-hospital mortality: IPA (OR 7.509, 95% CI 4.227-13.339, < 0.001), Voriconazole/Posaconazole treatment (OR 0.124, 95% CI 0.063-0.242, < 0.001), ICU hospitalization (OR 5.280, 95% CI 1.549-18.002, = 0.008), hematologic malignancy (OR 0.316, 95% CI 0.174-0.573, < 0.001), and NEU% ≥87.25% (OR 3.409, 95% CI 1.455-7.990, = 0.005).

CONCLUSION

Non-hematologic malignancy patients with IPA were frequently undertreated with antifungal therapy. A comprehensive diagnostic approach using biomarkers, CT, mycological evidence is crucial. Key risk factors for mortality include lack of Voriconazole/Posaconazole treatment, IPA diagnosis, ICU admission, non-hematologic malignancies, and elevated NEU%.

摘要

背景

侵袭性肺曲霉病(IPA)是由曲霉属物种引起的一种严重传染病。它与高死亡率相关,尤其是在免疫功能低下的患者中,以及患有COVID - 19肺炎的患者或重症监护病房(ICU)中的危重症患者中。准确的临床诊断仍然是一项重大挑战,常常导致漏诊。

方法

本研究评估了在12个月内通过真菌学证据和临床标准诊断为IPA的住院患者。纳入标准要求至少有一项真菌学结果为阳性,包括支气管肺泡灌洗液(BALF)或高质量痰液培养阳性,或半乳甘露聚糖抗原(GM)检测阳性。

结果

共有216例患者被诊断为IPA,死亡率为68.5%。血液系统恶性肿瘤是33.8%病例的主要基础疾病。总体而言,45%(98/216)的患者使用了伏立康唑或泊沙康唑,但非血液系统恶性肿瘤患者中只有26%(32/121)接受了这些治疗。接受伏立康唑/泊沙康唑治疗的患者28天生存率为0.776±0.038,未治疗患者为0.421±0.043。治疗患者的中位生存期为130天(95%CI,35.3 - 224.7),未治疗患者为20天(95%CI,15.8 - 24.2)(P<0.001)。IPA诊断的生物标志物显示出高诊断价值,GM、G、PCT、IL - 6、WBC、NEU%和D - 二聚体的曲线下面积(AUC)值分别为0.953、0.983、1.000、0.999、0.961、0.996和1.000。GM水平>0.5 pg/ml的阳性预测值为52.9%(27/51),而真菌学培养阳性的预测值为46.5%(33/71)。多变量回归分析确定了几个与院内死亡率相关的显著因素:IPA(OR 7.509,95%CI 4.227 - 13.339,P<0.001)、伏立康唑/泊沙康唑治疗(OR 0.124,95%CI 0.063 - 0.242,P<0.001)、入住ICU(OR 5.280,95%CI 1.549 - 18.002,P = 0.008)、血液系统恶性肿瘤(OR 0.316,95%CI 0.174 - 0.573,P<0.001)和NEU%≥87.25%(OR 3.409,95%CI 1.455 - 7.990,P = 0.005)。

结论

非血液系统恶性肿瘤的IPA患者抗真菌治疗常常不足。使用生物标志物、CT和真菌学证据的综合诊断方法至关重要。死亡的关键危险因素包括未接受伏立康唑/泊沙康唑治疗、IPA诊断、入住ICU、非血液系统恶性肿瘤以及NEU%升高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/b460e3196a9a/fmicb-16-1587227-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/ff912bafc6a2/fmicb-16-1587227-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/2b9c92624d71/fmicb-16-1587227-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/59815bd4af73/fmicb-16-1587227-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/5e90b2f40bd0/fmicb-16-1587227-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/b460e3196a9a/fmicb-16-1587227-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/ff912bafc6a2/fmicb-16-1587227-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/2b9c92624d71/fmicb-16-1587227-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/59815bd4af73/fmicb-16-1587227-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/5e90b2f40bd0/fmicb-16-1587227-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dacf/12078237/b460e3196a9a/fmicb-16-1587227-g0005.jpg

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