宏基因组二代测序技术在抗生素使用后的早产儿败血症中的应用

Application of metagenomic next-generation sequencing technology in preterm infants with sepsis following antibiotic use

摘要:

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.