目的 探讨宏基因组二代测序（metagenomic next-generation sequencing, mNGS）在抗生素使用后早产儿败血症病原学诊断中的价值。 方法 回顾性分析河南省人民医院收治的45例早产儿败血症患儿的病例资料，所有患儿均给予抗生素治疗≥3 d以上，且均进行了血培养及血mNGS检测，比较血培养及血mNGS检测对病原体检出率的差异。 结果 血mNGS检出病原阳性率高于血培养阳性率（44% vs 4%，P<0.001）。血mNGS检出病原体28株，其中细菌23株，真菌4株，细小脲原体1株。血培养检出近平滑假丝酵母菌及肺炎克雷伯杆菌各1例。抗生素使用时长>10 d组血mNGS阳性率高于血培养阳性率（40% vs 3%，P<0.001）；抗生素使用时长≤10 d组血mNGS阳性率也高于血培养阳性率（53% vs 7%，P=0.020）。有13例患儿依据血mNGS检测结果调整了治疗方案，治疗有效率为85%（11/13）。 结论 抗生素使用后的早产儿败血症中血mNGS检测病原阳性率高于血培养，且不受抗生素使用时长的影响，提示当临床高度怀疑存在病原微生物感染而血培养无法检出病原时可考虑行mNGS检测以明确病原。
Abstract
Objective To explore the value of metagenomic next-generation sequencing (mNGS) technology in the etiological diagnosis of sepsis in preterm infants following antibiotic use. Methods A retrospective analysis of medical records for 45 preterm infants with sepsis who were treated at Henan Provincial People's Hospital. All patients received antibiotic treatment for ≥3 days and underwent both blood culture and mNGS testing. The detection rates of pathogens by blood culture and mNGS testing were compared. Results The positive detection rate of pathogens by blood mNGS was higher than that by blood culture (44% vs 4%; P<0.001). Blood mNGS detected 28 strains of pathogens, including 23 bacteria, 4 fungi, and 1 Ureaplasma parvum. Blood culture identified one case each of Rhodotorula mucilaginosa and Klebsiella pneumoniae. In the group treated with antibiotics for >10 days, the positive rate of blood mNGS testing was higher than that of blood culture (40% vs 3%; P<0.001); similarly, in the group treated with antibiotics for ≤10 days, the positive rate of blood mNGS testing was also higher than that of blood culture (53% vs 7%; P=0.020). Treatment plans were adjusted based on blood mNGS results for 13 patients, with an effectiveness rate of 85% (11/13). Conclusions In preterm infants with sepsis following antibiotic use, the positive rate of pathogen detection by blood mNGS is higher than that by blood culture and is unaffected by the duration of antibiotic use. Therefore, mNGS testing can be considered for confirming pathogens when clinical suspicion of infection is high but blood culture fails to detect the pathogen.
关键词
败血症 /
宏基因组二代测序 /
抗生素 /
血培养 /
早产儿
Key words
Sepsis /
Metagenomic next-generation sequencing technology /
Antibiotic /
Blood culture /
Preterm infant
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参考文献
1 谢定泉. 新生儿败血症的诊疗研究进展[J]. 山西医药杂志, 2021, 50(14): 2209-2211. DOI: 10.3969/j.issn.0253-9926.2021.14.030.
2 Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study[J]. Lancet, 2020, 395(10219): 200-211. PMID: 31954465. PMCID: PMC6970225. DOI: 10.1016/S0140-6736(19)32989-7.
3 Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of paediatric and neonatal sepsis: a systematic review[J]. Lancet Respir Med, 2018, 6(3): 223-230. PMID: 29508706. DOI: 10.1016/S2213-2600(18)30063-8.
4 高瑛, 张磊, 赵子艳, 等. 极低及超低出生体重儿115例临床分析[J]. 中华实用诊断与治疗杂志, 2015, 29(12): 1207-1209. DOI: 10.13507/j.issn.1674-3474.2015.12.023.
5 He Y, Du WX, Jiang HY, et al. Multiplex cytokine profiling identifies interleukin-27 as a novel biomarker for neonatal early onset sepsis[J]. Shock, 2017, 47(2): 140-147. PMID: 27648693. DOI: 10.1097/SHK.0000000000000753.
6 Guerti K, Devos H, Ieven MM, et al. Time to positivity of neonatal blood cultures: fast and furious?[J]. J Med Microbiol, 2011, 60(Pt 4): 446-453. PMID: 21163823. DOI: 10.1099/jmm.0.020651-0.
7 《中华传染病杂志》编辑委员会. 中国宏基因组学第二代测序技术检测感染病原体的临床应用专家共识[J]. 中华传染病杂志, 2020, 38(11): 681-689. DOI: 10.3760/cma.j.cn311365-20200731-00732.
8 中华医学会儿科学分会新生儿学组, 中华儿科杂志编辑委员会. 宏基因组二代测序技术在新生儿感染性疾病中的临床应用专家共识[J]. 中华儿科杂志, 2022, 60(6): 516-521. PMID: 35658355. DOI: 10.3760/cma.j.cn112140-20220113-00046.
9 徐旻皓, 罗益, 陈鲜威. 早产儿晚发型败血症发病的相关因素研究[J]. 中国妇幼健康研究, 2021, 32(7): 949-952. DOI: 10.3969/j.issn.1673-5293.2021.07.004.
10 徐放, 申阿东. 宏基因组测序在儿童呼吸道感染性疾病研究中的应用[J]. 中华实用儿科临床杂志, 2020, 35(10): 783-786. DOI: 10.3760/cma.j.cn101070-20200413-00629.
11 Duan LW, Qu JL, Wan J, et al. Effects of viral infection and microbial diversity on patients with sepsis: a retrospective study based on metagenomic next-generation sequencing[J]. World J Emerg Med, 2021, 12(1): 29-35. PMID: 33505547. PMCID: PMC7790710. DOI: 10.5847/wjem.j.1920-8642.2021.01.005.
12 朱韵倩, 甘明宇, 张丽梅, 等. 宏基因组二代测序技术对新生儿脓毒症的诊断意义[J]. 中华新生儿科杂志, 2022, 37(3): 233-237. DOI: 10.3760/cma.j.issn.2096-2932.2022.03.009.
13 Miao Q, Ma Y, Wang Q, et al. Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice[J]. Clin Infect Dis, 2018, 67(suppl_2): S231-S240. PMID: 30423048. DOI: 10.1093/cid/ciy693.
14 Blauwkamp TA, Thair S, Rosen MJ, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease[J]. Nat Microbiol, 2019, 4(4): 663-674. PMID: 30742071. DOI: 10.1038/s41564-018-0349-6.
15 Grumaz S, Stevens P, Grumaz C, et al. Next-generation sequencing diagnostics of bacteremia in septic patients[J]. Genome Med, 2016, 8(1): 73. PMID: 27368373. PMCID: PMC4930583. DOI: 10.1186/s13073-016-0326-8.
16 Wang J, Han Y, Feng J. Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis[J]. BMC Pulm Med, 2019, 19(1): 252. PMID: 31856779. PMCID: PMC6921575. DOI: 10.1186/s12890-019-1022-4.
17 Grumaz S, Grumaz C, Vainshtein Y, et al. Enhanced performance of next-generation sequencing diagnostics compared with standard of care microbiological diagnostics in patients suffering from septic shock[J]. Crit Care Med, 2019, 47(5): e394-e402. PMID: 30720537. PMCID: PMC6485303. DOI: 10.1097/CCM.0000000000003658.
18 Li ZY, Dang D, Wu H. Next-generation sequencing of cerebrospinal fluid for the diagnosis of unexplained central nervous system infections[J]. Pediatr Neurol, 2021, 115: 10-20. PMID: 33310532. DOI: 10.1016/j.pediatrneurol.2020.10.011.
19 中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识（2019年版）[J]. 中华儿科杂志, 2019, 57(4): 252-257. PMID: 30934196. DOI: 10.3760/cma.j.issn.0578-1310.2019.04.005.
基金
河南省医学科技攻关项目（LHGJ20210011）。
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