应用血浆微生物游离DNA测序预测造血干细胞移植患者血流感染病原体被引量：1

Prediction of bloodstream infection pathogens in hematopoietic stem cell transplantation patients by plasma microbial cell-free DNA sequencing

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摘要目的通过血浆微生物游离DNA(mcfDNA)额外扩增和非额外扩增测序,预测造血干细胞移植(HSCT)患者血流感染(BSI)病原体。方法前瞻性采集2021年3—7月北京大学人民医院978例HSCT患者移植前预处理期至移植后4个月间的7428份临床剩余血样,分离血浆并冷冻保存。依据血培养结果和是否留有BSI发病前样本等,最终共纳入28例血培养阳性(39份BSI发病前1~8天的血浆)和9例血培养阴性(9份血浆)的HSCT患者。39份血浆样本进行mcfDNA额外扩增和非额外扩增测序;9份血浆样本进行额外扩增测序。以血培养结果为金标准,比较测序结果与血培养结果的一致性。使用Student t检验和Wilcoxon检验进行统计学分析。结果未经额外核酸扩增的测序分析显示,仅有7份样本的测序结果与血培养结果一致,总病原检出率为17.95%(7/39),发病前3天内和4~8天内的检出率分别为23.81%(5/21)和2/18。主要检出的病原类型为革兰阴性菌(5/7)。而经额外扩增测序的总病原检出率为59.26%(16/27),且BSI发病前3天内的检出率为8/13。与未经额外扩增测序相比,额外扩增测序结果中革兰阳性菌的检出增加(13/16),检测到额外微生物的数量显著增加(t=3.440,P=0.001)。此外,血培养阴性患者9份血浆样本的额外扩增测序结果显示,6份样本均未检出病原体,3份样本仅检出HSCT患者常见的细环病毒。结论HSCT患者BSI发病前血浆mcfDNA额外扩增测序的病原体检出率优于非额外扩增测序,且在前3天内的检出率更高,具有预测BSI病原体的潜能。 Objective To predict the pathogens of bloodstream infection(BSI)in hematopoietic stem cell transplantation(HSCT)patients by plasma microbial cell-free DNA(mcfDNA)sequencing with and without additional amplification.Methods A total of 978 HSCT patients were enrolled in Peking University People′s Hospital from March to July 2021,and the 7428 blood samples were prospectively collected from pretransplant conditioning period to 4 months after transplantation.The plasma samples were separated and then cryopreserved.According to blood culture results and whether there were plasma samples before BSI onset,twenty-eight HSCT patients with positive blood culture(39 plasma samples within 1-8 days before BSI onset)and 9 HSCT patients with negative blood culture(9 plasma samples)were filtered.The 39 samples were performed with mcfDNA additional and non-additional amplification sequencing,and the 9 samples were only performed with additional amplification sequencing.With the blood culture results as the gold standard,the consistency between the sequencing and the blood culture results was observed.Student t test and Wilcoxon test were used for statistical analysis.Results Without additional amplification sequencing,only 7 samples sequencing results were consistent with the blood culture results,and the total pathogen detection rate was 17.95%(7/39).The rates within 3 days and 4-8 days were 23.81%(5/21)and 2/18,respectively.The main pathogenic type detected was gram-negative bacteria(5/7).With additional amplification sequencing,the total pathogen detection rate was 59.26%(16/27)and the rate within 3 days was 8/13.The number of gram-positive bacteria detected was elevated(13/16)and the number of additional microorganisms in additional amplification sequencing was increased significantly(P=0.0010),compared with non-additional amplification sequencing.Moreover,additional sequencing analysis of 9 samples from patients with negative culture result showed that no pathogen was detected in six samples,and the common Torque teno virus

作者殷冠坤韩秉宜陈宏斌马帅王辉 Yin Guankun;Han Bingyi;Chen Hongbin;Ma Shuai;Wang Hui(Institute of Medical Technology,Peking University Health Science Center,Beijing 100191,China)

机构地区北京大学医学部医学技术研究院北京大学人民医院检验科

出处《中华检验医学杂志》 CAS CSCD 北大核心 2022年第12期1267-1274,共8页 Chinese Journal of Laboratory Medicine

基金国家杰出青年科学基金(81625014)。

关键词造血干细胞移植血流感染病原体预测微生物游离DNA测序 Hematopoietic stem cell transplantation Bloodstream infection Pathogen Prediction Microbial cell-free DNA sequencing

分类号 R457.7 [医药卫生—治疗学]