宏基因组二代测序在非HIV感染患者耶氏肺孢子菌肺炎诊疗中的应用

Application of metagenomic next-generation sequencing in the diagnosis and treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected patients

目的:探讨宏基因组二代测序(mNGS)在非人类免疫缺陷病毒(HIV)感染患者中耶氏肺孢子菌肺炎(PJP)的诊断价值和其对治疗的指导价值。方法:采用回顾性研究方法,共纳入武汉大学中南医院2017年1月至2022年7月非HIV感染PJP患者73例和诊断为非PJP患者70例。分析了支气管肺泡灌洗液(BALF)中耶氏肺孢子菌(PJ)和其他共病原体情况,以临床复合诊断为参考标准,比较mNGS、聚合酶链式反应(PCR)和血清1,3‑β‑D‑葡聚糖(BDG)在PJP中的诊断效能,将纳入研究的PJP患者根据是否行mNGS分为行mNGS组和未行mNGS组,通过非参数秩和检验对比两组治疗情况。结果:本研究共纳入非HIV感染PJP患者73例,其中46例患者行mNGS检测,统计分析结果显示,相较于PCR、BDG,mNGS在诊断非HIV感染PJP的灵敏度(97.8%)和特异度(95.2%)更高。同时,mNGS在混合感染的检出率明显高于传统病原学检测(87.0%vs 63.0%,P=0.018),其中以白色念珠菌、人类疱疹病毒5型(CMV)、人类疱疹病毒1型(HSV1)最为常见。并且,在46例患者mNGS结果回报后,71.7%的PJP患者对最初的治疗方案进行了调整,其中57.6%患者经调整治疗方案后好转出院。与未行mNGS检测的非HIV感染PJP患者相比,行mNGS的患者住院时间更短[16(9,24)d vs 26(16,41)d],抗生素疗程更短[12(6,16)d vs 20(11,31)d],差异均有统计学意义(均P<0.05)。结论:mNGS对非HIV感染PJP的诊断效能高,且对于共病原体检出具有更好的性能,对临床诊断和指导针对性抗感染药物治疗具有一定的价值。

Objective:To investigate the diagnostic value of metagenomic next‑generation sequencing(mNGS)in Pneumocystis jirovecii pneumonia(PJP)in non‑human immunodeficiency virus(HIV)‑infected patients and its guiding value for treatment.Methods:PJP patients were divided into mNGS group and non‑mNGS group according to whether they received mNGS or not,and the treatment of the two groups was compared by non‑parametric rank test.Results:A total of 73 patients with non‑HIV infection PJP were included in this study,among which 46 patients were tested for mNGS.Statistical analysis results showed that mNGS had higher sensitivity(97.8%)and specificity(95.2%)in the diagnosis of non‑HIV‑infected PJP as compared with PCR and BDG.Meanwhile,the detection rate of mNGS in mixed infection was significantly higher than that of traditional etiological detection(87.0%vs 63.0%,P=0.018),among which candida albicans,human herpesvirus type 5(CMV)and human herpesvirus type 1(HSV1)were the most common.Moreover,after the mNGS results of 46 patients were received,the initial treatment regimen was adjusted in 71.7% of the PJP patients,and 57.6% of the patients improved and were discharged after adjusting the treatment plan.Compared with non‑HIV‑infected PJP patients who did not undergo mNGS testing,the patients who received mNGS had a shorter length of hospital stay(16(9,24)d vs 26(16,41)d)and a shorter course of antibiotics(12(6,16)d vs 20(11,31)d)with statistically significant difference(all P<0.05).Conclusion:mNGS has high diagnostic efficacy in non‑HIV PJP and has better performance for the detection of co‑pathogens,which has value for clinical diagnosis and guidance of targeted anti‑infective drug treatment.