Comparing three ways to clear antibiotic-resistant bacteria from the gut

Multicenter, Randomized, Open-label, Three-arm Study on the Efficacy of Fecal Microbiota Transplantation vs Probiotic Therapy vs Eubiotic-gut-microbiota-boosting Diet in Order to Antibiotic-resistant Bacteria (ARB) Decolonization From the Gastrointestinal Tract of Patients Colonized With Clinically Most Significant ARBs. Looking for a Strategy to Overcome the WHO Alarm on the Antibiotic Resistance "New Pandemic" Threat. STOP-ARB Study

This will test whether fecal microbiota transplantation after a short course of antibiotics, a multi-strain probiotic given after antibiotics, or a diet that boosts healthy gut bacteria best clears antibiotic‑resistant germs from the intestines of adults who carry them.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical University of Warsaw (Academic / other)
• Locations: 1 site (Warsaw)
• Trial ID: NCT07094984 on ClinicalTrials.gov

What this trial studies

This open-label, randomized 2:1:1 study will enroll about 360 adults with documented gastrointestinal colonization by clinically significant antibiotic‑resistant bacteria. Participants will be assigned to receive fecal microbiota transplantation (FMT) after a 5‑day targeted antibiotic course and bowel cleansing, a multi‑strain probiotic regimen given after the same antibiotic pre‑treatment and cleansing, or an active comparator diet designed to promote eubiotic gut flora. FMT will be delivered as standardized capsules or by colonoscopy on specified days, while probiotic dosing and dietary guidance will follow predefined protocols. The primary outcome is eradication of the target resistant organisms from stool or rectal swabs over follow‑up, with safety and adverse events also tracked.

Who should consider this trial

Good fit: Adults (≥18 years) with documented intestinal colonization confirmed by at least two positive rectal swabs or stool cultures, with the most recent positive result at least 28 days before the planned procedure, and colonization by clinically significant resistant strains (e.g., carbapenem‑resistant Enterobacteriaceae, MDR Pseudomonas or Acinetobacter, VRE, or MRSA).

Not a fit: People without gastrointestinal colonization by resistant organisms, those with active invasive infections that need immediate treatment, or individuals with contraindications to antibiotics, bowel prep, FMT, probiotics, or colonoscopy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, one or more of these approaches could reduce gut carriage of dangerous drug‑resistant bacteria, lowering the risk of future infections and limiting their spread.

How similar studies have performed: Small studies and case reports have shown that FMT can clear carriage of some resistant organisms in selected patients, but large randomized comparisons are limited and probiotic or diet‑only approaches have shown inconsistent results.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years;
* Documented intestinal colonization with antibiotic-resistant bacteria confirmed by at least two positive cultures (rectal swabs or, alternatively, stool cultures), with the last positive result obtained at least 28 days prior to the planned procedure;
* Documented colonization by one or more of the following bacterial strains:

  1. Carbapenem-resistant strains with confirmed resistance mechanisms, including MBL+ (NDM+, VIM+, or others), KPC+, OXA-48+, or phenotypic carbapenem resistance without identified genetic mechanism;
  2. Multidrug-resistant Enterobacteriaceae resistant to beta-lactams and other antibiotics, especially ESBL-producing strains, including Escherichia, Enterobacter, Klebsiella spp., and/or P. aeruginosa, A. baumannii (commonly associated with the ESKAPE group);
  3. Gram-positive bacteria such as Enterococcus faecalis, Enterococcus faecium, or other vancomycin-resistant enterococci (VRE), as well as Staphylococcus aureus strains resistant to methicillin (MRSA) and/or vancomycin;
* Absolute neutrophil count (ANC) in peripheral blood \>500/μL within 3 days prior to FMT; In case of tandem or repeated FMTs and expected neutrophil decline, the ANC test should be repeated before each FMT if the interval exceeds 3 days.

For patients without expected neutropenia (\<500/μL), the blood count remains valid for 28 days;

* Estimated life expectancy of at least 12 months;
* Ability to swallow large capsules (confirmed using a test capsule) or absence of contraindications to colonoscopy;
* No history of anaphylactic shock due to food allergies and ability to tolerate probiotic supplementation;
* Provision of written informed consent to participate in the study.

Exclusion Criteria:

* Lack of consent to participate in the study or inability to establish logical contact and obtain consent from an authorized representative;
* Absolute neutrophil count (ANC) \< 500 cells/μL on the day of FMT (within 3 days prior) or predicted decline to this level within the next 2 days;
* Diagnosed HIV infection with CD4 lymphocyte count \< 250 cells/μL;
* Active infection requiring antibiotic therapy on the day of FMT or planned antibiotic use during the first 7 days following FMT;
* Symptoms or radiological/endoscopic evidence of gastrointestinal mucosal damage within 7 days prior to FMT (e.g., ulceration, perforation, gastrointestinal bleeding) posing a risk of serious adverse events;
* Contraindications for FMT administration via upper or lower gastrointestinal tract routes (e.g., gastrointestinal perforation, anal atresia, lack of intestinal continuity, or other);
* Inability to undergo preparatory therapy (oral antibiotics: colistin, vancomycin, gentamicin and/or bowel cleansing agents) prior to FMT;
* Inability to swallow large capsules (confirmed with test capsules) or contraindications for colonoscopy;
* Severe food allergy with history of anaphylactic shock or inability to tolerate probiotics;
* Pregnancy or breastfeeding;
* Severe medical conditions contraindicating study protocol adherence as determined by the treating physician (e.g., severe heart failure precluding bowel cleansing due to risk of fluid overload or dehydration);
* Participation in another clinical trial and administration of an investigational drug or device within 3 months prior to randomization;
* Reluctance or inability to comply with protocol requirements, including any physical, mental, or social condition that may impair the participant's ability to adhere to the protocol.

Where this trial is running

Warsaw

• Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego, Klinika Hematologii, Transplantologii i Chorób Wewnętrznych — Warsaw, Poland (Recruiting)

Study contacts

• Study coordinator: Jaroslaw Bilinski, MD PhD, Assoc. Prof.

Conditions Drug Resistance, Bacterial; Antimicrobial Drug Resistance; Fecal Microbiota Transplantation; FMT; Antibiotic-resistant bacteria decolonization; Eradication procedure; probiotic therapy; eubiotic diet