宏基因组二代测序技术在假体周围感染中寻找病原菌的应用和价值

Application and Value of Metagenomic Sequencing Technology in Searching Pathogenic Bacteria in Periprosthetic Infection

目的探讨宏基因组二代测序技术(metagenomic next-generation sequencing,mNGS)在假体周围感染(prosthetic joint infection,PJI)病原菌检测中的作用和价值。方法收集2019年1月至2021年1月由西安市红会医院关节外科收治的因PJI或无菌性松动(aseptic loosening,AL)行关节翻修手术的患者60例,38例膝关节及22例髋关节。PJI组42例,男16例,女26例;年龄29~82岁,平均(64.33±13.03)岁;AL组18例,男6例,女12例;年龄44~85岁,平均(62.50±9.78)岁。采用常规细菌培养和mNGS检测患者关节液或滑膜组织标本中的病原菌。比较使用mNGS检测和常规细菌培养对关节液或滑膜组织标本PJI诊断的敏感性、特异性、阳性预测值、阴性预测值、一致率和检测时间的差异。进一步选取于2017年1月至2018年12月仅行常规培养阴性的PJI患者20例,作为经验性抗生素组(empirical antibiotic group,EA);2019年1月至2021年1月行mNGS检测的20例PJI患者作为靶向抗生素组(targeted antibiotic group,TA)。对两组进行至少6个月的随访,统计两组在抗生素使用时间、住院抗生素花费及不良反应例数及复发病例的差异。结果42例PJI患者中,细菌培养阳性为30例,mNGS检测阳性为40例。18例AL患者中细菌培养阳性为2例,mNGS阳性有7例;细菌培养共检出12种病原菌,mNGS共检出31种病原菌。细菌培养组和mNGS组的敏感性、特异性、阳性预测值、阴性预测值和一致率分别为71.4%、94.4%、93.8%、33.3%、60.0%和95.2%、61.1%、85.1%、84.6%、85.0%。mNGS组的检出时间(1.87±0.39)d明显短于培养组(5.55±0.65)d。两组在敏感度、特异度、一致率及检出时间上比较,差异均有统计学意义(P<0.05)。TA组静脉抗生素使用时间为(10.15±1.50)d,抗生素费用为(6149.15±763.06)元;对照组EA组静脉抗生素使用时间为(14.52±2.00)d,抗生素治疗费用为(10874.70±1353.63)元。两组在静脉抗生素使用时间及治疗花费上比较,差异均具有统计学意义(P<0.05)。结论mNGS可以有效地识别PJI患者的病原菌,与传统培养相比具有更高的灵敏度和一致率,在检出时间和抗生素花费上更具优势,在PJI的诊断中具有更高的诊断效率,可在PJI的诊断和治疗中提供有力的临床指导。

Objective To investigate the role and value of metagenomic sequencing technology in detection of pathogenic bacteria around prosthesis.Methods 60patients,including 38knee patients and 22hip patients with prosthetic joint infection(PJI)or aseptic loosening were enrolled in the Department of Joint Surgery,Xi’an Honghui Hospital from January 2019to January 2021.All patients were older than 18years old.There were 42cases in PJI group,including 16males and 26females with an average age of(64.33±13.03).There were 18cases in AL group,including 6males and 12females with an average age of(62.50±9.78).Conventional bacterial culture and mNGS were used to detect pathogenic bacteria in joint fluid or synovial tissue samples from patients.The sensitivity,specificity,positive predictive value,negative predictive value,consistency rate,and detection time of PJI in articular fluid or synovial tissue specimens were compared between mNGS and conventional bacterial culture.Twenty PJI patients who received only negative conventional culture from January 2017to December 2018were further selected as the empirical antibiotic group.Twenty PJI patients who underwent mNGS testing from January 2019to January 2021 were included in the targeted antibiotic group.The two groups were followed up for at least 6months,and the differences between the two groups in the time of antibiotic use,the cost of antibiotics in hospital,the number of adverse reactions and recurrence cases were counted.Results Among 42PJI patients,30 were positive in bacterial culture and 40 were positive in mNGS.Among the 18AL patients,2were positive for bacterial culture and 7were positive for mNGS.A total of 12 kinds of pathogenic bacteria were detected in bacterial culture and 31kinds of pathogenic bacteria were detected in mNGS.The sensitivity,specificity,positive predictive value,negative predictive value and consistency rate of bacterial culture group and mNGS group were 71.4%,94.4%,93.8%,33.3%,60.0%and 95.2%,61.1%,85.1%,84.6%,85.0%,respectively.The detection time of mNGS group was significantly shorter(1.87±0.39)d In culture group(5.55±0.65)d.There were statistically significant differences in sensitivity,specificity,coincidence rate and detection time between the two groups(P<0.05).The duration of intravenous antibiotics in TA group was(10.15±1.50)d,and the antibiotic cost was(6149.15±763.06)yuan.The duration of intravenous antibiotics in control group EA was(14.52±2.00)d,and the antibiotic treatment cost was(10874.70±1353.63)yuan.There were statistically significant differences in the time of intravenous antibiotic use and treatment cost between the two groups(P<0.05).Conclusion mNGS can effectively identify the pathogenic bacteria of PJI patients.Compared with traditional culture,mNGS has higher sensitivity and consistency rate,more advantages in detection time and antibiotic cost,higher diagnostic efficiency in the diagnosis of PJI,and can provide powerful clinical guidance in the diagnosis and treatment of PJI.