Fecal Microbiota Transplantation (FMT) for MDRO UTI

Multidrug resistant organism (MDRO) infections are increasingly common. The most common type of infection caused by MDROs is urinary tract infections (UTIs). Many MDROs are inhabitants of the colon, and MDROs can contaminate the periurethral area and migrate to the bladder. Patients with MDRO UTI frequently experience multiple relapses and hospitalizations, which both increase the individual's morbidity and mortality and leads to additional MDRO nosocomial spread. There are few options available to prevent MDRO UTIs, and there are limited strategies to identify patients at risk for recurrent MDRO UTI and prevent or reverse MDRO colonization. A potential novel method to reverse MDRO colonization and prevent recurrent UTI would be by repopulating the gut microbiome with "healthy" microbiota by fecal microbiota transplantation (FMT).

In this study, participants with a history of severe, recurrent MDRO UTI will receive FMT. Participants will submit stool and urine specimens pre- and post-FMT, and the effect of FMT on the participants' fecal and urine microbiome, urine metabolome, persistent MDRO colonization, and risk of recurrent UTI will be evaluated.

• Fecal microbiota transplant (Drug), also known as Stool transplant: 150mL of FMT product RBX2660 delivered via enema

Primary outcomes

• Number of Patients With Adverse Events During and After FMT [Six months post-FMT]: The number, types, severity, and relation of adverse events to study procedures or product will be analyzed.

Secondary outcomes

• Number of Patients With Recurrent UTI Post-FMT [Six months post-FMT]: Risk of recurrent UTI post-FMT will be evaluated

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years old.
* Outpatient status at time of FMT.
* History of at least three recurrent UTIs due to an MDRO; at least two recurrent, severe infections due to MDRO requiring hospitalization; or at least two recurrent infections due to MDRO for which only antimicrobials with rate limiting toxicities (see above) are available.
* Be without active infection due to the MDRO at the time of FMT.
* Not be receiving antimicrobials (therapeutic or suppressive) within 48 hours of FMT.

Exclusion Criteria:

* Age <18 years
* Inpatient status at time of FMT
* Ineligible UTI
* >1 organism in urine (other than minimal contaminants)
* Decline to participate
* Recurrent Clostridium difficile infection
* Presence of intra-abdominal devises
* Neutropenia (ANC <500 mm3)
* Intestinal mucosal disruption
* Unlikely to survive 6 months
* Pregnancy or unwillingness to use contraceptives
* Short gut syndrome
* Use of medications that affect intestinal motility
* Gastrointestinal motility disorder
* Inflammatory bowel disease
* Recent abdominal surgery
* Active typhlitis
* Active diverticulitis
* Current gastrointestinal graft versus host disease
* HIV with lack of antiretroviral therapy (ART)
* CD4 count <200 mm3
* Peritoneal dialysis
* Cirrhosis with ascites
* Active intra-abdominal malignancy
* Presence of chronic indwelling foley catheter, chronic suprapubic catheter, or ileal conduit
* Active hepatitis C
* Active hepatitis B
* Presence of ureteral stent
* Active kidney stone that is believed to be a persistent source of bacterial colonization
* Any condition where the investigator feels the risks of FMT outweigh the benefits

Participant flow

Outcome results

• Number of Patients With Adverse Events During and After FMT (Primary), Count of participants, Participants: FMT for MDRO UTI 1
• Number of Patients With Recurrent UTI Post-FMT (Secondary), Count of participants, Participants: FMT for MDRO UTI 1

Adverse events

Time frame: 6 months

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2018-08-22)

• Erik Dubberke, MD, MSPH, Principal investigator, Washington University School of Medicine