Monitoring of Antimicrobial Resistance Based on Metagenomics Analyses in Pneumonia Patients: a Genomic Epidemiology Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 1
- 主要终点
- Microbiome composition
研究概览
简要总结
Monitoring of antimicrobial resistance (AMR) based on metagenomics analyses in pneumonia patients is critical for optimizing clinical diagnosis and treatment and improving clinical prognosis. This study is designed to ask the following key questions:
- What is the microbiome maps of patients with severe pneumonia and mild pneumonia ?
- How many pathogen resistance genes are carrying in severe pneumonia and mild pneumonia ?
- What is the genetic diversity of key pathogens detected in severe pneumonia and mild pneumonia during 2019-2025?
详细描述
This is a historical prospective obsevational study. Patients diagnosed with severe and mild pneumonia are recruited continously from four hospitals (Shanghai General Hospital, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuhan Union Hospital, and Huanggang Central Hospital) in China during March, 2019 to March, 2025.
Next-generation sequencing: Metagenomics and metatranscriptomic libraries undergo next-generation sequencing using the Illumina Novaseq 6000 platform.
Microbiome analysis: using KneadData (v0.10.0) reference from the human genome (GRCH38 reference database) to filter out the quality control of illumina sequencing data in Virosaurus download virus genome data sets for reference, bowtie2 (v2.3.4.1) (genome coverage >30%, depth >1X) was used to locate and analyze the post-host sequence, and then the "samtools idxstats" command was used to calculate the classification and relative abundance of viruses. Meanwhile, in order to obtain the annotation information of bacteria at the species level, PhyloFlash (v3.4) was used to calculate read counts for 16S rRNA genes in the SILVA database, selecting similarity greater than or equal to 98% as a threshold. Using eukaryotic pathogen genome database EUPATHDB46 as reference, bowtie2 and samtools were used for qualitative and quantitative analysis of fungal pathogens.
The criteria for determining the cause of respiratory infection are: (1) existing species known to be associated with human disease (ICD-10), (2) previously unidentified potential novel pathogens (only DNA and RNA viruses whose genera or families have previously been shown to infect mammals), and (3) possible symbiotic bacteria not included.
Analysis of AMR: by comparing the sequence similarity between the sequencing fragments and known drug resistance genes, the detection content can determine whether drug resistance genes exist, and suggest drug resistance caused by modification, inactivation, repression and other drug resistance genes.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients clinically diagnosed as severe pneumonia and mild pneumonia are diagnosed according to the Guidelines for the diagnosis and Treatment of community-acquired pneumonia in Adults (2019 edition) formulated by the American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA), who meet 1 of the following major criteria or ≥3 minor criteria can be diagnosed. The diagnostic criteria for severe and mild pneumonia in children were adopted by the British Thoracic Society (BTS) in
- •Clinical examination was performed, and there was biospecimen (nasopharyngeal swab, oropharyngeal swab, bronchoalveolar lavage fluid, sputum, blood, hydrothorax, lung tissue) remaining in the clinical microbiological examination.
排除标准
- •Patients whose biological samples may be contaminated;
- •Patients with alveolar lavage fluid or hydrothorax volume less than 200μl.
结局指标
主要结局
Microbiome composition
时间窗: during the study period, 2019-2025
a collection of microbial communities detected in the biospecimen
次要结局
- Alpha diversity(during the study period, 2019-2025)
- Prevalence of bacterial resistance genes(during the study period, 2019-2025)
- Beta diversity(during the study period, 2019-2025)
研究者
Mei Kang
Principal Investigator
Shanghai General Hospital, China