Bacteriuria, Multidrug-Resistant Bacterial Infections, Recurrent Urinary Tract Infections, Urinary Tract Infections
Conditions
Keywords
Washed microbiota transplantation, Fecal microbiota transplantation, Multidrug-resistant organism, Recurrent urinary tract infection
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALWashed Microbiota Transplantation (WMT)
Participants will receive washed microbiota transplantation delivered via colonic transendoscopic enteral tubing (TET) for 3 times. The WMT preparation follows the Nanjing Consensus on Washed Microbiota Transplantation (Chin Med J, 2020). Donor fecal material is obtained from healthy screened donors and processed using the GenFMTer intelligent separation system with repeated washing and quality control. The final microbiota suspension is transplanted into the colon through an indwelling TET tube.
Sponsors
The Second Hospital of Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years, both sexes. 2. Recurrent UTI (symptomatic UTI or asymptomatic bacteriuria), with ≥2 episodes in the past 6 months or ≥3 episodes in the past year. 3. 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). 4. Physically eligible and willing to receive colonic TET tube placement and WMT treatment. 5. Able to provide informed consent and comply with scheduled follow-up visits and specimen collection.
Exclusion criteria
1. Received effective antimicrobial therapy within 48 hours before WMT. 2. Unable to tolerate colonoscopy or TET tube placement. 3. Severe comorbidities with expected survival less than 6 months. 4. Pregnant or lactating women. 5. Other conditions deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of microbiological success | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to microbiological success | Up to 6 months | Time from the first WMT to the first of two consecutive negative urine cultures for the baseline pathogen. |
| Number of UTI recurrence episodes | Up to 6 and 12 months | Number of symptomatic UTI episodes during the follow-up period. |
| Baseline to day 7 | Up to 12 months | Clinical manifestations of acute UTI episodes and antibiotic usage during follow-up. |
| Quality of life score measured by the 36-Item Short Form Health Survey (SF-36) | Baseline and 6 months | Changes in quality of life scores measured by the 36-Item Short Form Health Survey (SF-36) from baseline to 6 months post-WMT. The SF-36 consists of eight subscales: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each subscale is scored from 0 to 100, with higher scores indicating a better outcome (better health-related quality of life). |
| Change in white blood cell count | Baseline to day 7 | Change in peripheral blood white blood cell count, expressed as ×10\^9/L, from baseline to days 4 and 7 post-WMT. |
| Change in hemoglobin | Baseline to day 7 | Change in peripheral blood hemoglobin, expressed as g/L, from baseline to days 4 and 7 post-WMT. |
| Change in platelet count | Baseline to day 7 | Change in peripheral blood platelet count, expressed as ×10\^9/L, from baseline to days 4 and 7 post-WMT. |
| Change in urine white blood cell count | Baseline to day 7 | Change in urine white blood cell count on microscopy, expressed as cells per high-power field, from baseline to days 4 and 7 post-WMT. |
| Change in urine nitrite | Baseline to day 7 | Change in urine nitrite on dipstick, expressed as positive or negative, from baseline to days 4 and 7 post-WMT. |
| Change in C-reactive protein (CRP) | Baseline to day 7 | Change in serum C-reactive protein, expressed as mg/L, from baseline to days 4 and 7 post-WMT. |
| Change in procalcitonin (PCT) | Baseline to day 7 | Change in serum procalcitonin, expressed as ng/mL, from baseline to days 4 and 7 post-WMT. |
| Change in alanine aminotransferase (ALT) | Baseline to day 7 | Change in serum alanine aminotransferase, expressed as U/L, from baseline to days 4 and 7 post-WMT. |
| Change in aspartate aminotransferase (AST) | Baseline to day 7 | Change in serum aspartate aminotransferase, expressed as U/L, from baseline to days 4 and 7 post-WMT. |
| Change in total bilirubin | Baseline to day 7 | Change in serum total bilirubin, expressed as µmol/L, from baseline to days 4 and 7 post-WMT. |
| Change in serum creatinine | Baseline to day 7 | Change in serum creatinine, expressed as µmol/L, from baseline to days 4 and 7 post-WMT. |
| Change in blood urea nitrogen (BUN) | Baseline to day 7 | Change in blood urea nitrogen, expressed as mmol/L, from baseline to days 4 and 7 post-WMT. |
Countries
China
Outcome results
None listed