目的 探讨宏基因组二代测序（metagenomic next-generation sequencing，mNGS）技术在血液肿瘤患儿感染性疾病病原体诊断中的应用价值。 方法 回顾性分析2020年6月—2022年7月于中南大学湘雅三医院收治的因感染行微生物培养及mNGS的43例血液肿瘤疾病患儿的临床资料及病原学检测结果，比较mNGS与微生物培养法病原体检出率的差异及病原学特征。 结果 43例患儿共采集54份标本送检，mNGS的病原体总检出率（80%，43/54）高于微生物培养法（30%，16/54），差异有统计学意义（P<0.001）。mNGS最常检出的感染类型为病毒感染，其次是真菌合并病毒感染；微生物培养最常见的感染类型为细菌感染，其次为真菌感染。mNGS真菌检出率（33%，18/54）高于微生物培养法（6%，3/54），差异有统计学意义（P<0.001）。mNGS与微生物培养法对2种或2种以上病原体感染的检出率（48% vs 9%）和2类或2类以上病原体感染检出率（33% vs 2%）的比较差异均有统计学意义（均P<0.05）。mNGS在外周血中最常检出的细菌、真菌分别为铜绿假单胞菌、热带念珠菌；在支气管肺泡灌洗液中最常检出的细菌、真菌为肺炎链球菌、耶氏肺孢子菌。35%（15/43）的患儿根据mNGS结果调整治疗并获益。 结论 mNGS比微生物培养法有更高的检出率，且对混合感染、真菌感染有明显优势，可作为微生物培养法的有益补充。
Abstract
Objective To explore the value of metagenomic next-generation sequencing (mNGS) in the pathogen identification in children with hematological malignancies complicated with infections. Methods A retrospective analysis was conducted on clinical data and pathogenic test results of 43 children with hematological malignancies who underwent microbial culture and mNGS due to infections in the Third Xiangya Hospital of Central South University between June 2020 and July 2022. Differences in detection rates and characteristics of pathogenic microorganisms detected by mNGS and microbial culture were compared. Results A total of 54 specimens were examined, and the overall detection rate of pathogen by mNGS (80%, 43/54) was significantly higher than that by microbial culture (30%, 16/54) (P<0.001). The most commonly detected infection type by mNGS was viral infection, followed by fungal infection combined viral infection, while that by microbial culture was bacterial infection, followed by fungal infection. The detection rate of fungi by mNGS (33%, 18/54) was higher than that by microbial culture (6%, 3/54) (P<0.001). The detection rate of two or more pathogenic microorganisms by mNGS was higher at 48% compared to microbial culture at 9% (P<0.05). The detection rate of two or more types of pathogenic microorganisms by mNGS was also significantly higher at 33% compared to microbial culture at 2% (P<0.05). The most commonly detected bacteria and fungi by mNGS were Pseudomonas aeruginosa and Candida tropicalis, respectively, in peripheral blood, while Streptococcus pneumoniae and Pneumocystis jirovecii were most commonly detected in bronchoalveolar lavage fluid. Treatment adjustments based on mNGS results were beneficial for 35% (15/43) of the cases. Conclusions mNGS has a higher detection rate than microbial culture and has obvious advantages in diagnosing mixed and fungal infections, making it a useful supplementary diagnostic method to microbial culture.
关键词
血液肿瘤疾病 /
宏基因组二代测序 /
感染 /
病原学检测 /
儿童
Key words
Hematological malignancy /
Metagenomic next-generation sequencing /
Infection /
Pathogen detection /
Child
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基金
湖南省自然科学基金杰出青年基金项目（2021JJ10077）；国家自然科学基金（82270185）；湖南省科技创新计划项目（2022RC3077）。
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