Application of metagenomic next-generation sequencing in the diagnosis and treatment of refractory urinary tract infections: report of 3 cases
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摘要: 尿路感染是泌尿外科的常见疾病，然而许多患者表现为顽固性、难治性或慢性尿路感染症状，对生活与工作造成巨大影响。目前临床中的常用检测为尿常规、中段尿培养等，存在较高的假阴性发生率。宏基因组测序高通量测序(mNGS)以往多应用于肿瘤和遗传病诊断，在尿路感染方面尚未开展，本研究探索了mNGS在顽固性尿路感染治疗中的应用价值。3例顽固性尿路感染女性患者，年龄分别为25、26和57岁，尿常规、尿三杯和中段尿培养无明显病原体证据，经过经验性用药无明显缓解。患者进行中段尿液样本采集和mNGS检测，通过基因序列分析细菌、真菌、病毒等基因，并提供耐药基因报告。随后进行敏感性药物应用，每周进行随访，收集患者主诉和尿常规、尿培养报告。治疗成功标准为患者主诉下尿路症状好转、尿常规和尿培养阴性。3例患者的mNGS检测均发现了多种微生物感染和耐药基因，使用敏感抗生素治疗后症状明显好转。以上病例提示，mNGS能够发现常规尿液检查无法获得的病原微生物数据和耐药基因数据，对指导临床药物选择、缩短患者感染病程、减少抗生素的经验性滥用有促进作用，可作为常规病原学检测无法解释的复杂性尿路感染，以及排除病因不明的下尿路症状患者的可选性检测方法。Abstract: Urinary tract infection is a common disease in urology. However, many patients show intractable, refractory or chronic infection syndrome, which has a great impact on their life and work. At present, the commonly used methods of clinical detection are urine routine test, midstream urine culture, etc., which have a large false negative incidence. Metagenomic next-generation sequencing(mNGS) has been used for the diagnosis of tumors and genetic diseases in the past, but has not been carried out in urinary tract infections. This study explored the application value of mNGS in the treatment of refractory urinary tract infections. Three female patients with refractory urinary tract infection, aged 25, 26 and 57 years, respectively, underwent urine routine test, but no obvious evidence of pathogens was found in the urine three-cup or midstream urine cultures, or no significant remission was found after empirical medication. The midsteam urine samples were collected and mNGS tests were performed. Bacterial, fungal, viral and other genes were analyzed by gene sequence, and drug resistance gene reports were provided. Subsequently, sensitive drug and weekly follow-up were performed. Patient complaints, urine routine tests, urine culture reports were collected. Treatment success criteria were improvement of patient complaints in lower urinary tract symptoms and negative urine routine and urine culture. MNGS detection of the three patients found a variety of microbial infections and drug resistance genes, and the symptoms were significantly improved after treatment with sensitive antibiotics. Results of these cases suggest that mNGS can find pathogenic microbial data and drug resistance gene data that cannot be obtained by routine urine examination. MNGS can promote the selection of clinical drugs, shorten the course of infection, and reduce the empirical abuse of antibiotics, so it can be applied to complex urinary tract infection that cannot be explained by routine pathogenic testing. It can also be an optional test to exclude patients with other lower urinary tract symptoms without clear etiology.
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表 1 患者mNGS检测微生物情况
病例 微生物名称 标化计数 病例1 高度可以致病病原 铜绿假单胞菌 263 三重分枝杆菌 20 近平滑假丝酵母 300 JC病毒 349 需关注的潜在病原 大肠埃希菌 59 黑曲霉 28 耐药基因预测 四环素 病例2 高度可以致病病原 粪肠球菌 675 人乳头瘤病毒90型 640 JC病毒 250 需关注的潜在病原 铜绿假单胞菌 41 近平滑假丝酵母 9 耐药基因预测 大环内酯类 病例3 高度可以致病病原 大肠埃希菌 1 199 657 弗劳第柠檬酸杆菌 74 531 肠道沙门氏菌 61 733 无乳链球菌 6706 
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