宏基因组二代测序对肾脏重症监护病房免疫功能低下患者感染的诊断价值

Metagenomic next-generation sequencing for infections in immunosuppressed patients in renal intensive care unit

目的:回顾性分析宏基因组二代测序(mNGS)对肾脏重症监护病房(ICU)免疫功能低下患者感染的诊断价值,评估临床应用前景。方法:选取2018年8月至2022年4月国家肾脏疾病临床医学研究中心ICU收治疑诊感染的慢性肾脏病(CKD)免疫功能低下患者,分为常规微生物学检测(CMT)确诊感染组、临床诊断感染组和排除感染组,对比mNGS与CMT的诊断效能。结果:本研究共纳入303例患者,累计使用2(1,3)种免疫抑制剂,中位治疗时间7(2,50)月,中位CD4^(+)T细胞计数149.50(81.25,262.25)个/μL,在院死亡率20.46%。CMT确诊感染组中38.79%的mNGS与CMT结果完全一致,27.88%部分一致,33.33%不一致。临床诊断感染组中57.69%通过mNGS发现感染病原体。mNGS报阳时间更早,检测病原体种类更多(P<0.05),混合感染检出率高(P<0.001),可鉴定出常规培养难以发现的病原体。mNGS对感染病原体检测灵敏度和准确度强于CMT(P=0.014),特异度、阳性及阴性预测值无明显差异。结论:mNGS能增加免疫功能低下的CKD患者感染病原体检测的灵敏度和准确度,缩短报阳时间,提高混合感染、机会性感染、罕见感染病原体检出率。

Objective:This retrospective study was to evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing(mNGS)for infections in immunosuppressed patients of renal intensive care unit(ICU).Methodology:We retrospectively analyzed immunosuppressed chronic kidney disease(CKD)patients suspected of infection admitted to the ICU of National Clinical Research Center of Kidney Diseases,Jinling Hospital from August 2018 to April 2022.We divided them into conventional microbiological tests(CMT)confirmed infection group,clinically diagnosed infection group and exclusion of infection group,and then compared the microbiological detection efficiency between mNGS and CMT.Results:The 303 patients involved in this study used 2(1,3)types of immunosuppressants,with a median time of 7(2,50)months.The median CD4^(+)T value was 149.50(81.25,262.25)/μL,and the in-hospital mortality was 20.46%.In the CMT confirmed infection group,38.79%of mNGS were completely consistent with CMT results,accompanied by 27.88%partially consistent with 33.33%inconsistent.In the clinically diagnosed infection group,57.69%of infected pathogens could be detected by mNGS.We found that mNGS outperformed culture in terms of tested positive time and the high microbial detection.The sensitivity and accuracy of mNGS in infection diagnosis were much higher than that of CMT.Nevertheless,there was no significant difference in specificity,positive and negative predictive values.Conclusion:mNGS can improve the sensitivity and accuracy of infection pathogen detection in immunosuppressed CKD patients.mNGS is emerging as a promising technique to detect co-pathogens in infection with potential benefits in speed and sensitivity,which may provide more diagnostic evidence in opportunistic infection or rare infection pathogens.