The aim of this research experiment is to evaluate the effectiveness of fecal microbiota transplantation (FMT) preceded by antibiotic pre-treatment versus probiotic therapy and a standard-of-care equivalent diet designed to stimulate the growth of eubiotic gut microbiota (an active comparator enhancing the ethical value of the study and increasing the chances of spontaneous decolonization of antibiotic-resistant bacteria (ARB) in the absence of any active intervention recommended by Scientific Societies) in the decolonization of bacteria with the most clinically significant antibiotic resistance mechanisms from the gastrointestinal tract of colonized patients.
This study addresses the urgent need highlighted by the World Health Organization (WHO) for new strategies to combat antibiotic resistance, aiming to prevent its progression into a global pandemic that could undermine the achievements of modern civilization.
Study Hypotheses:
* The decolonization rate of ARB bacteria in patients undergoing the intervention (FMT or probiotic therapy) is the same as in patients treated with standard-of-care (SoC) alone. * The decolonization rate of ARB bacteria in the intervention groups (FMT or probiotic therapy) is at least 20 percentage points higher than in patients treated with the standard approach (diet).
The findings from this study may contribute to developing innovative microbiota-based therapies for the decolonization of antibiotic-resistant bacteria and help reduce the global burden of antibiotic resistance.
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;
Carbapenem-resistant strains with confirmed resistance mechanisms, including MBL+ (NDM+, VIM+, or others), KPC+, OXA-48+, or phenotypic carbapenem resistance without identified genetic mechanism;
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);
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;
Parallel
Fecal microbiota transplantation (FMT)
Other interventionFMT administered after antibiotic pre-treatment and bowel cleansing. Delivered either in capsule form or via colonoscopy to restore healthy gut microbiota and support decolonization of ARB.
Probiotic Therapy
Dietary supplementOral administration of a high-dose multistrain probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus strains for 20 days following bowel cleansing.
Gut Microbiota Boosting Diet
Other interventionA structured 38-day diet designed to promote eubiosis and support spontaneous ARB decolonization. Meals are tailored and delivered to patients based on clinical nutrition protocols.
Complete decolonization of gastrointestinal antibiotic-resistant bacteria (ARB)
Proportion of participants achieving complete decolonization of ARB from the gastrointestinal tract, defined as at least two consecutive negative rectal swab cultures (or stool cultures), taken at least one day apart, at day 60 following completion of the eradication procedure. Bacterial resistance mechanisms include ESBL, CRE, VRE, and MRSA. If available, PCR confirmation of absence of resistance genes is required for final classification as eradicated.
Complete decolonization of ARB at days 30, 90, and 180
Proportion of participants with complete decolonization of gastrointestinal ARB, confirmed by at least two negative rectal swab or stool cultures taken at least one day apart, at days 30, 90, and 180 following the end of intervention. PCR confirmation of eradication is required when baseline colonization was confirmed by PCR.
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Medical University of Warsaw
Lead sponsor
Human Biome Institute S.A.
Collaborator
Medical Research Agency, Poland
Collaborator
