A Prospective, Single-Center, Single-Arm Clinical Study of Washed Microbiota Transplantation for Multidrug-Resistant Organism Urinary Tract Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Rate of microbiological success
研究概览
简要总结
This is a single-center, prospective, single-arm, exploratory clinical study to evaluate the efficacy, safety, and potential mechanisms of washed microbiota transplantation (WMT) in patients with recurrent urinary tract infections caused by multidrug-resistant organisms (MDRO-UTI). With increasing antimicrobial resistance, MDRO UTI becomes refractory and poses a significant therapeutic challenge. WMT may reconstruct gut microbiota, reduce uropathogen colonization, decrease antibiotic resistance gene burden, and modulate host immunity and metabolism. Approximately 10 eligible patients will receive WMT delivered via colonic transendoscopic enteral tubing (TET) for 3 times according to the Nanjing Consensus on Washed Microbiota Transplantation. Participants will be followed for up to 12 months with clinical, microbiological, metagenomic, metabolomic, and immunological assessments.
详细描述
This study aims to assess whether WMT can achieve microbiological eradication of baseline MDRO pathogens and reduce UTI recurrence. Donor stool will be obtained from healthy screened donors and processed using the GenFMTer intelligent fecal microbiota separation system with strict quality control and washing procedures. Patients will receive WMT via colonic TET for 3 sessions.
Assessments include: (1) Microbiological: clean-catch midstream urine culture and antimicrobial susceptibility testing at baseline, days 4 and 7, and months 1, 3, 6, and during acute episodes; (2) Laboratory: blood routine, urine routine, CRP, procalcitonin, liver and kidney function at baseline and days 4 and 7; (3) Quality of life: SF-36 questionnaire at baseline and month 6; (4) Safety: adverse events throughout follow-up; (5) Multi-omics: fecal and urine metagenomic sequencing (alpha/beta diversity, taxonomic composition, SourceTracker colonization analysis, StrainGE strain tracking, antibiotic resistance genes, and UPEC virulence genes including FimH, PapG, CsgBAC, BarA, UvrY); serum/urine LC-MS metabolomics (untargeted and targeted); serum cytokines by ELISA (IL-6, IL-10, IL-22, IFN, GM-CSF, Eotaxin-1/CCL11); lymphocyte subsets and CD4/CD8 by flow cytometry; urinary secretory IgA by radioimmunoassay. Bioinformatic analyses including LefSe, ROC curves, and OPLS-DA will be used for integrative analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years, both sexes.
- •Recurrent UTI (symptomatic UTI or asymptomatic bacteriuria), with ≥2 episodes in the past 6 months or ≥3 episodes in the past year.
- •Clean-catch midstream urine culture at enrollment showing bacterial colony count ≥10^5 CFU/ml, with multidrug-resistant organism (non-susceptible to ≥3 antimicrobial categories, including resistant and intermediate).
- •Physically eligible and willing to receive colonic TET tube placement and WMT treatment.
- •Able to provide informed consent and comply with scheduled follow-up visits and specimen collection.
排除标准
- •Received effective antimicrobial therapy within 48 hours before WMT.
- •Unable to tolerate colonoscopy or TET tube placement.
- •Severe comorbidities with expected survival less than 6 months.
- •Pregnant or lactating women.
- •Other conditions deemed unsuitable for enrollment by the investigator.
研究组 & 干预措施
WMT Treatment Group
干预措施: Washed Microbiota Transplantation (WMT) (Biological)
结局指标
主要结局
Rate of microbiological success
时间窗: Up to 6 months
Microbiological success is defined as two consecutive negative clean-catch midstream urine cultures for the baseline pathogen during the follow-up period. Microbiological failure is defined as growth of the baseline pathogen at ≥10\^5 CFU/ml at the last follow-up urine culture.
次要结局
- Time to microbiological success(Up to 6 months)
- Number of UTI recurrence episodes(Up to 6 and 12 months)
- Baseline to day 7(Up to 12 months)
- Quality of life score measured by the 36-Item Short Form Health Survey (SF-36)(Baseline and 6 months)
- Change in white blood cell count(Baseline to day 7)
- Change in hemoglobin(Baseline to day 7)
- Change in platelet count(Baseline to day 7)
- Change in urine white blood cell count(Baseline to day 7)
- Change in urine nitrite(Baseline to day 7)
- Change in C-reactive protein (CRP)(Baseline to day 7)
- Change in procalcitonin (PCT)(Baseline to day 7)
- Change in alanine aminotransferase (ALT)(Baseline to day 7)
- Change in aspartate aminotransferase (AST)(Baseline to day 7)
- Change in total bilirubin(Baseline to day 7)
- Change in serum creatinine(Baseline to day 7)
- Change in blood urea nitrogen (BUN)(Baseline to day 7)
研究者
Faming Zhang
Professor, Gastroenterology
The Second Hospital of Nanjing Medical University