Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP): protocol for a multi-centre, randomized, placebo-controlled feasibility pilot trial

Abstract Background: Antimicrobial resistance (AMR) is a threat to effective treatment of bacterial infections. Gastrointestinal colonization with an antimicrobial resistant organism (ARO) is a risk factor for subsequent systemic infection, and increasing resistance is associated with increased infection recurrence. Patient-level interventions to decrease or minimize antimicrobial harms and reduce gastrointestinal colonization and translocation without worsening selection for AMR have tremendous potential for clinical impact. Despite the prevalence and mortality associated with bloodstream infections, there are no effective therapies for decolonization of the gut microbiome in attempts to potentially decrease the risk of recurrence. Reconstituting the perturbed microbiome is a novel therapeutic modality with the potential to decrease ARO colonization and subsequent infection and combat AMR without additional selection pressure for further AMR. No clinical trial has yet assessed the potential of a therapeutic microbial consortium for ARO decolonization and infection prevention after antibiotic treatment. Methods: Antimicrobial Resistant Organism Decolonization After Microbiome Perturbation (ARO-DECAMP) is a multi-centre, placebo-controlled, pilot randomized controlled feasibility trial using the microbial consortium Microbial Ecosystem Therapeutic-2. Non-intensive care unit hospitalized patients >18 years of age receiving antibiotic treatment for a bloodstream infection caused by an ARO will be included. Participants will be randomized in a 1:1 ratio to receive either MET-2 or placebo for 10 days, with treatment initiation 2-3 days after completion of antibiotics. Participants will be followed for 180 days, and biological samples will be collected periodically for clinical, ecological, and biomarker outcomes. Recruitment rate and study intervention adherence will be evaluated for feasibility. Discussion: This study is designed to determine if a trial of administration of microbial consortia after antibiotic treatment for bloodstream infections is feasible. Results of this pilot study will inform the design and sample size of a definitive trial powered to assess the effectiveness of the intervention as a therapeutic strategy for augmenting the microbiome and improving clinical outcomes. Trial registration: ClinicalTrials.gov, NCT06214403. Registered 19 January 2024, https://clinicaltrials.gov/study/NCT06214403