A Multicenter Prospective Protocol to Explore the Relationship Between Enterococcus faecalis Bloodstream Infections and Colorectal Neoplasms (EnteroColonus-GAMES Project)

Preliminary evidence suggests that patients with Enterococcus faecalis bacteremia and infective endocarditis, particularly those without an identifiable source, may have an increased prevalence of colorectal neoplasia. Whether systematic colonoscopy should be recommended in this population remains unresolved. EnteroColonus is a multicenter, prospective, observational matched cohort study that will recruit adults aged 50 years or older with E. faecalis bacteremia and/or infective endocarditis from 22 Spanish centers, together with asymptomatic controls undergoing colorectal cancer screening. Cases will be stratified into E. faecalis bacteremia/endocarditis of unknown origin (EFBEUO) and with suspected source (EFBESS). The original planned sample size initially was 414 participants: 276 cases and 138 matched controls. Under the amended protocol, the current confirmatory sample-size target is 165 participants (110 cases and 55 matched controls; 2:1 case-to-control allocation). Core procedures include colonoscopy, histopathology, clinical and microbiological phenotyping of colonic samples, fecal microbiome profiling by shotgun metagenomics, detection of E. faecalis genetic material in colorectal biopsy specimens using 16S sequencing and species-specific qPCR, and whole-genome, SNP, and phylogenetic analyses of clinical isolates. Secondary endpoints include microbiome profiles, biopsy positivity for E. faecalis, genomic traits of bloodstream isolates, mortality, relapse/recurrence, and development of a colorectal neoplasia risk score. This protocol is designed to clarify which patients with E. faecalis bloodstream infection might benefit from systematic colonoscopy evaluation and to explore host–microbe mechanisms underlying the observed association with colorectal neoplasia.