摘要
目的 评价以宏基因组高通量测序(mNGS)诊断血液病患者中侵袭性真菌病(IFD)感染的临床特点及相关风险因素.方法 纳入2022年1月至2023年1月70例住院血液病患者,疑诊IFD者行mNGS及真菌病原学检查,对比32例检出真菌感染者(IFD组)和38例非IFD组之间的临床特点和实验室数据.结果 经mNGS检测确定的IFD组发现念珠菌15例(47％)、曲霉菌6例(19％),根毛霉菌4例(12.5％)和孢子菌4例(12.5％),其他3例(9％).血液标本36例中经mNGS检出11例(30.6％)阳性;而真菌微生物培养仅3例(8.3％),阳性检出率差异具有统计学意义(P=0.017).经多因素logistic回归分析,与IFD相关的风险因素为CD4+细胞计数低于400个/μL[OR 7.43,95％CI 7.43(2.46～22.44),P＜0.001]、C反应蛋白增高[OR3.71,95％CI3.71(1.33～10.32),P=0.01]、IL-6升高[OR6.5,95％CI6.50(2.27～18.62),P＜0.001]、IL-10增高[OR 3.03,95％CI3.03(1.03～8.94),P=0.041]、低白蛋白血症[OR 7.04,95％CI 7.04(1.40～35.56),P=0.025]及粒细胞缺乏持续 10d 以上[OR3.03,95％CI3.03(1.03～8.94),P=0.002].结论 mNGS检测血液病患者中IFD敏感性高;CD4+细胞计数低于400个/μL、C反应蛋白增高、IL-6升高、IL-10增高、低白蛋白血症及粒细胞缺乏持续10 d以上是血液病患者发生IFD的独立风险因素.
Abstract
Objective To evaluate the clinical characteristics and related risk factors of invasive fungal disease(IFD)in patientswith blood diseases diagnosed by high-throughput metagenomic sequencing(mNGS).Methods From January 2022 to January 2023,70 hospitalized patients with blood diseases who were suspected of infection with IFD underwent mNGS and fungal pathogen detection.The clinical characteristics and laboratory data of 32 fungal infected individuals(IFD group)and 38 non IFD groups were compared.Results In the IFD group,15 cases(47％)of Candida,6 cases(19％)of Aspergillus,4 cases(12.5％)of Rhizopus,4 cases(12.5％)of Spores,and 3 other cases(9％)were detected by mNGS.Out of 36 blood samples,11(30.6％)were positive by mNGS;However,there were only 3 cases(8.3％)of fungal microbial culture,with a significant difference in positive detection rate(P=0.017).Using traditional fungal culture results as the"gold standard",the sensitivity,specificity,positive predictive value,and negative predictive value of mNGS for evaluating fungal infection in hematological patients were calculated,and the results were 100％(10/10),63.3％(38/60),31.3％(10/32),and 100％(38/38),respectively.After multiple logistic regression analysis,the risk factors associated with IFD were:CD4+cell count below 400 cells/μL[OR 7.43,95％CI 7.43(2.46-22.44),P＜0.001],increased level of C-reactive protein[OR 3.71,95％CI 3.71(1.33-10.32),P=0.01],IL-6[OR 6.5,95％CI6.50(2.27-18.62),P＜0.001]and IL-10[OR 3.03,95％CI 3.03(1.03-8.94),P=0.041],hypoalbuminemia[OR 7.04,95％CI 7.04(1.40-35.56),P=0.025]and sustained neutropenia lasting for more than 10 days[OR 3.03,95％CI 3.03(1.03-8.94),P=0.002].Conclusion mNGS has high sensitivity in detecting IFD in patients with hematological diseases.CD4+cell count below 400/μL,increased level of C-reactive protein,IL-6,and IL-10,hypoalbuminemia,and neutropenia lasting for more than 10 days are independent risk factors for IFD in patients with hematological diseases.
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