737. Novel Glycans Reduce Carbapenem-Resistant Enterobacteriaceae and Vancomycin-Resistant Enterococci Colonization in an Ex Vivo Assay by Supporting Growth and Diversity of Commensal Microbiota at the Expense of MultiDrug-Resistant Organisms (MDRO)

Abstract

BackgroundInfections with Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococci (VRE) can result in a 50% mortality rate in compromised hosts. A major risk factor for clinical infection is intestinal colonization with CRE or VRE. There are currently no FDA-approved compounds to decolonize these organisms from the gastrointestinal tract (gut). Commensal microbes offer protection from pathogen infection; however, in immunocompromised hosts or with antibiotic treatment, the protective properties of the microbial community are compromised, leaving the gut susceptible to pathogen colonization. Higher concentrations of pathogens within the gut correlate with an increased risk of infection with MDROs. Our hypothesis is that reducing colonization of the gut with MDROs would reduce the likelihood of a clinical infection.MethodsKaleido built a platform that emulates the gut environment and allows for high throughput screening of Kaleido’s Microbiome Metabolic Therapies (MMT™) in human gut microbiomes ex vivo. Over 500 compounds were screened for their ability to reduce the levels of CRE and VRE in fecal microbial communities from both healthy subjects and critically ill patients receiving broad-spectrum antibiotics.ResultsKaleido’s lead MMTs selectively favor the growth of the commensal microbiota at the expense of pathogens, resulting in a decrease of CRE and VRE from 80% of the initial community to 5% in a single batch culture, as measured by 16S rRNA gene and shotgun metagenomic sequencing. Lead MMTs do not support growth of CRE and VRE strains in culture, nor of other pathogens frequently encountered in critically ill and immunocompromised patients, such as Clostridium difficile and common fungal pathogens.ConclusionThese results suggest that intervention with MMTs may reduce CRE and VRE colonization and support further evaluation in patients colonized with CRE or VRE pathogens. Disclosures All authors: No reported disclosures.