Clinical Application Of Metagenomic Next-Generation Sequencing In Non-Immunocompromised Patients With Severe Pneumonia Supported By Veno-Venous Extracorporeal Membrane Oxygenation. VV-ecomo-XXL

Objectives: This study aims to investigate the pathogen-detected effect and clinical therapy value of mNGS technologies in non-immunocompromised patients with severe pneumonia supported by vv-ECMO. Methods: The study retrospectively enrolled 50 non-immunocompromised patients with severe pneumonia supported by vv-ECMO from January 2016 to December 2022. Patients were categorized into two groups based on their discharge status: deterioration group (Group D) (n = 31) and improvement group (Group I) (n = 19). Baseline characteristics and clinical data were collected, including information on pathogens and antibiotic regimens. Results: Out of 50 ECMO patients enrolled, the group D had more male gender (80.6% vs. 52.6%, p < 0.05) , more smoking (54.8% vs. 21.1%, p < 0.05) and was older than group I (55.16±16.34 years vs. 42.32±19.65 years, p < 0.05). 64 samples underwent mNGS detection with 55 (85.9%) testing positive, 83.7%(36/43) in group D, 90.5%(19/21) in group I. Additionally, the positive rate of traditional culture was 64.9% (74/114). Out of 54 samples tested with both culture and mNGS, 23 (42.6%) had consistent pathogen identification, 13 (24.1%) were partially consistent, and 18 (33.3%) were completely inconsistent. Among the inconsistent ones, 14 (77.8%) were negative for culture while two each (11.1%) were negative for mNGS or mismatched. However, mNGS detected more pathogens and strains than traditional culture (65 strains vs. 23 strains), including 56 in group D, 26 in group I and 17 overlapping strains. The most frequently detected pathogens by mNGS were Klebsiella Pneumoniae, Cytomegalovirus, and Acinetobacter baumannii. A variety of G+ bacteria, fungi, viruses, and specific pathogens were detected only in group D, while Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were higher in group D than in group I. mNGS led to the antibiotic treatment adjustment in 26 patients (52.0%) . Conclusions: mNGS has a distinct advantage in detecting mixed pathogens and guiding personalized antibiotic treatment for non-immunocompromised patients with severe pneumonia supported by vv-ECMO, which may help alleviate the issues of excessive antibiotic use, antimicrobial resistance, and misuse of medical resources.

研究目的：本研究旨在探讨宏基因组二代测序（metagenomic next-generation sequencing, mNGS）技术在接受静脉-静脉体外膜肺氧合（veno-venous extracorporeal membrane oxygenation, vv-ECMO）支持的非免疫功能低下重症肺炎患者中的病原体检出效能与临床治疗价值。
研究方法：本研究回顾性纳入2016年1月至2022年12月期间的50例接受vv-ECMO支持的非免疫功能低下重症肺炎患者。依据患者出院转归将其分为两组：恶化组（D组，n=31）与改善组（I组，n=19）。收集患者的基线特征与临床资料，涵盖病原体相关信息及抗菌药物治疗方案。
研究结果：纳入的50例ECMO支持患者中，D组男性占比更高（80.6% vs 52.6%，p<0.05）、吸烟比例更高（54.8% vs 21.1%，p<0.05）且平均年龄更大（55.16±16.34岁 vs 42.32±19.65岁，p<0.05）。共计64份样本接受mNGS检测，其中55份（85.9%）检测结果为阳性：D组阳性率为83.7%（36/43），I组阳性率为90.5%（19/21）。此外，传统培养的阳性率为64.9%（74/114）。在同时接受培养与mNGS检测的54份样本中，23份（42.6%）的病原体鉴定结果一致，13份（24.1%）结果部分一致，18份（33.3%）结果完全不一致。在结果不一致的样本中，14份（77.8%）培养结果为阴性，2份（11.1%）mNGS结果为阴性，另有2份（11.1%）出现匹配不符的情况。相较传统培养技术，mNGS检出的病原体与菌株数量更多（65株 vs 23株），其中D组检出56株，I组检出26株，两组重叠检出菌株17株。mNGS最常检出的病原体为肺炎克雷伯菌、巨细胞病毒与鲍曼不动杆菌。多种革兰氏阳性菌、真菌、病毒及特殊病原体仅在D组中检出；鲍曼不动杆菌、铜绿假单胞菌与肺炎克雷伯菌在D组中的检出率显著高于I组。mNGS促使26例患者（52.0%）调整了抗菌药物治疗方案。
研究结论：对于接受vv-ECMO支持的非免疫功能低下重症肺炎患者，mNGS在检出混合病原体与指导个性化抗菌药物治疗方面具有显著优势，或有助于缓解抗菌药物过度使用、抗菌药物耐药及医疗资源误用等临床问题。