宏基因组二代测序对重症社区获得性肺炎患者的病原学诊断及预后分析

Pathogenic diagnosis and impact on the prognosis of metagenomic next-generation sequencing in patients with severe community-acquired pneumonia

目的评价宏基因组二代测序(mNGS)对重症社区获得性肺炎(SCAP)患者病原微生物的检测能力及对预后影响。方法采用回顾性研究方法。选择2018年3月至2022年12月入住安徽医科大学附属省立医院重症医学科并接受支气管肺泡灌洗液(BALF)mNGS的65例SCAP患者,并与同期仅进行传统病原学检测(CMT)的患者按1∶1配对,配对标准为性别、年龄差值在5岁以内、基础疾病、免疫状态、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)差值在3分以内、肺炎严重指数(PSI)评分。观察的主要终点为90 d病死率;次要终点包括重症监护病房(ICU)住院时间、机械通气时间、7 d内肺炎好转率、28 d病死率,并绘制Kaplan-Meier生存曲线比较两组90 d累积生存率。结果CMT组有16例(24.62%)阴性结果,而mNGS组仅有1例(1.54%)阴性结果(P<0.05)。在收到微生物学检测报告后,mNGS组有42例患者(64.62%)进行了抗感染方案的调整,而CMT组只有18例(27.69%)进行了调整(P<0.05)。mNGS组检测到的细菌总数显著高于CMT组(49株比25株,P<0.05)。mNGS组患者真菌检出总数高于CMT组(14株比5株,P<0.05)。mNGS组和CMT组所检出的病毒总数差异无统计学意义(6株比8株,P>0.05)。mNGS组中41例患者(63.08%)在随后的7 d内肺部感染的情况得到改善,而CMT组中只有24例患者(36.92%)得到改善(P<0.05)。mNGS组机械通气时间(d:6.64±1.53比6.84±1.28,P<0.05)和ICU住院时间(d:8.68±1.78比9.28±1.66,P<0.05)均显著短于CMT组,mNGS组患者的28 d病死率(16.92%比36.92%,P<0.05)和90 d病死率(24.62%比43.08%,P<0.05)也显著低于CMT组。Kaplan-Meier生存曲线显示,mNGS组90 d累积生存率明显高于CMT组(Log-Rank检验:χ^(2)=7.528,P=0.026)。结论mNGS对SCAP患者的病原微生物学较CMT有更高的检测能力,临床医师据此选择了更合适的治疗方案,也间接改善了患者预后。

Objective To evaluate the effect of metagenomic next-generation sequencing(mNGS)on the diagnostic ability of pathogenic microorganisms and prognosis of patients with severe community-acquired pneumonia(SCAP).Methods A retrospective study was conducted.A total of 65 patients with SCAP admitted to the department of critical care medicine of the Affiliated Provincial Hospital of Anhui Medical University from March 2018 to December 2022 who received bronchoalveolar lavage fluid(BALF)mNGS were collected.They were matched in a ratio of 1∶1 with patients who only underwent conventional microbiological tests(CMT)during the same period.The matching criteria were sex,age(the difference is within 5 years),underlying disease,immune status,acute physiology and chronic health evaluationⅡ(APACHEⅡscore,the difference is within 3 points),and pneumonia severity index(PSI).The primary endpoint of observation was 90-day mortality,while the secondary outcomes included length of intensive care unit(ICU)stay,mechanical ventilation duration,efficacy of treatment of pulmonary infection within 7 days,and 28-day mortality,Kaplan-Meier survival curve was drawn to compare the 90-day cumulative survival rate between the two groups.Results In the CMT group,there were 16(24.62%)negative results,whereas only 1(1.54%)had negative results in the mNGS group(P<0.05).After receiving the microbiological report,antibiotics were altered in 42 patients(64.62%)in the mNGS group,but in only 18(27.69%)in the CMT group(P<0.05).The total number of bacteria detected in mNGS group was significantly higher than that in CMT group(strains:49 vs.25,P<0.05).Total number of the fungal detection in mNGS group was higher than that in CMT group(strains:14 vs.5,P<0.05).There was no significant difference in the total number of viruses detected between the two groups(strains:6 vs.8,P>0.05).In the mNGS group,41 patients(63.08%)showed improvement in pulmonary infection within 7 days,compared to only 24 patients(36.92%)in the CMT group(P<0.05).The mechanical ventilation duration(days:6.64±1.53 vs.6.84±1.28,P<0.05)and length of ICU stay(days:8.68±1.78 vs.9.28±1.66,P<0.05)in mNGS group were significantly shorter than those in CMT group.The 28-day(16.92%vs.36.92%,P<0.05)and 90-day mortality rates(24.62%vs.43.08%,P<0.05)were also significantly lower in the mNGS group than those in the CMT group.Kaplan-Meier survival curve showed the 90-day cumulative survival rate in mNGS group was significantly higher than that in CMT group(Log-Rank test:χ^(2)=7.528,P=0.026).Conclusion mNGS has a higher ability to detect pathogenic microbiology in SCAP patients than CMT,so clinicians can choose a more appropriate treatment plan based on this and indirectly improves the prognosis of these patients.