Fecal microbiota transplant for treating antibiotic-resistant infections

A Phase II Randomized Trial to Evaluate the Impact of Fecal Microbiota Transplantation Using the Penn Microbiome Therapy Products on Recipient and Environmental Colonization With Multidrug-Resistant Organisms

This study is testing if a fecal microbiota transplant can help people with tough infections caused by antibiotic-resistant bacteria get better when they are also on standard antibiotics.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT05632315 on ClinicalTrials.gov

What this trial studies

This Phase II trial investigates the effectiveness of fecal microbiota transplant using Penn Microbiome Therapy (PMT) products in eradicating multidrug-resistant bacteria in patients undergoing standard antibiotic treatment. The study is randomized and open-label, focusing on patients with infections caused by specific antibiotic-resistant organisms, including certain strains of Enterobacteriaceae, Pseudomonas aeruginosa, VRE, and MRSA. Participants must be receiving appropriate antibiotic therapy and have a qualifying MDRO infection. The goal is to determine if PMT can enhance the eradication of these resistant bacteria compared to standard treatment alone.

Who should consider this trial

Good fit: Ideal candidates are patients with bloodstream, respiratory, or urinary tract infections caused by specific multidrug-resistant organisms who are on appropriate antibiotic therapy.

Not a fit: Patients with infections not caused by the specified multidrug-resistant organisms or those not on appropriate antibiotic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients suffering from difficult-to-treat multidrug-resistant infections.

How similar studies have performed: Other studies have shown promise in using fecal microbiota transplants for various conditions, but this specific application for multidrug-resistant infections is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Multidrug-resistant organism (MDRO) infection of the bloodstream, respiratory tract, or urinary tract. Qualifying MDROs include extended-spectrum cephalosporin-resistant Enterobacterales (ESCRE) or carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa non-susceptible to two or more classes of antibiotics (MDR-PA), vancomycin-resistant Enterococcus (VRE), and methicillin-resistant Staphylococcus aureus (MRSA).
2. On appropriate antibiotic treatment per clinical phenotypic susceptibility testing of the qualifying MDRO, and with a qualifying antibiotic class. Qualifying antibiotic classes include beta-lactam + beta-lactamase inhibitor, carbapenem (with or without betalactamase inhibitor), fluoroquinolone, lipopeptide, glycopeptide, or oxazolidinone.
3. Expected duration of inpatient antibiotic treatment for index MDRO infection at least 5 days total.
4. At least two calendar days remaining, and no more than 7 calendar days remaining prior to SCAIM (scheduled completion of inpatient appropriate antibiotics for the index MDRO infection).
5. Age ≥ 18 years.

Exclusion Criteria:

1. Evidence of colon/small bowel perforation at the time of study screening.
2. Unable to tolerate enteral and enema nutrition and medication administration (i.e., only able to tolerate intravenous nutrition and medications).
3. Goals of care are directed to comfort rather than curative measures.
4. Moderate or severe neutropenia within 10 calendar days prior to enrollment.
5. Known food allergy that could lead to anaphylaxis.
6. Known allergy to fecal microbiota transplant products or their components
7. Pregnancy or lactation

   1. For subjects of childbearing potential (ages 18 to 55) and who are randomized to receive the intervention, the subject must have a negative pregnancy test within 24 hours prior to product administration
   2. Female or male subjects (ages 18 to 55) of reproductive potential engaged in active sexual activity that could lead to a pregnancy must agree to use one of the following forms of birth control while receiving study medications and through day 28 following completion of treatment, at minimum:

   i. Male or female condoms

   ii. Diaphragm or cervical cap with spermicide, if available

   iii. Intrauterine device (IUD)

   iv. Oral contraceptives or other hormonal contraception
8. Known gastrointestinal disease that could affect the safety of fecal microbiota transplant at time of enrollment:

   1. Inflammatory Bowel Disease (IBD)
   2. Short Gut Syndrome
   3. Fistulas
   4. Bowel resection surgery
   5. Colitis

Where this trial is running

Philadelphia, Pennsylvania

• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Brendan J Kelly — University of Pennsylvania
• Study coordinator: Brendan J Kelly, MD, MS

Conditions: Multidrug Resistant Bacterial Infection, Enterobacteriaceae Infections, Pseudomonas Aeruginosa, VRE Infection, Methicillin-resistant Staphylococcus Aureus