WMT for Multidrug-Resistant Organism UTI

The Second Hospital of Nanjing Medical University10 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

Interventions

Washed Microbiota Transplantation (WMT)BIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Rate of microbiological success

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.

Time frame: Up to 6 months

Secondary Outcomes

Time to microbiological success

Time from the first WMT to the first of two consecutive negative urine cultures for the baseline pathogen.

Time frame: Up to 6 months

Number of UTI recurrence episodes

Number of symptomatic UTI episodes during the follow-up period.

Time frame: Up to 6 and 12 months

Baseline to day 7

Clinical manifestations of acute UTI episodes and antibiotic usage during follow-up.

Time frame: Up to 12 months

Quality of life score measured by the 36-Item Short Form Health Survey (SF-36)

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).

Time frame: Baseline and 6 months

Change in white blood cell count

Change in peripheral blood white blood cell count, expressed as ×10\^9/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in hemoglobin

Change in peripheral blood hemoglobin, expressed as g/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in platelet count

Change in peripheral blood platelet count, expressed as ×10\^9/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in urine white blood cell count

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.

Time frame: Baseline to day 7

Change in urine nitrite

Change in urine nitrite on dipstick, expressed as positive or negative, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in C-reactive protein (CRP)

Change in serum C-reactive protein, expressed as mg/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in procalcitonin (PCT)

Change in serum procalcitonin, expressed as ng/mL, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in alanine aminotransferase (ALT)

Change in serum alanine aminotransferase, expressed as U/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in aspartate aminotransferase (AST)

Change in serum aspartate aminotransferase, expressed as U/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in total bilirubin

Change in serum total bilirubin, expressed as µmol/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in serum creatinine

Change in serum creatinine, expressed as µmol/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

Change in blood urea nitrogen (BUN)

Change in blood urea nitrogen, expressed as mmol/L, from baseline to days 4 and 7 post-WMT.

Time frame: Baseline to day 7

WMT for Multidrug-Resistant Organism UTI

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes