PMT for MDRO Decolonization

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 is a randomized, open label, comparative Phase II trial being conducted to determine whether fecal microbiota transplant using Penn Microbiome Therapy (PMT) products helps standard therapy eradicate antibiotic-resistant bacteria.

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