2580. Serial Microbiome Analysis in a Patient with Multiple Failed Fecal Microbiome Transplantations

BACKGROUND: Fecal microbiota transplantation (FMT) is recommended to treat refractory or recurrent cases of Clostridioides difficile infection (CDI) through restoration of a healthy intestinal microbiome. The procedure has reported success rates of 90% or higher for CDI, but several risk factors for FMT failure have been identified. Here we present a case of a patient failing four FMT procedures over a 2-year period, with accompanying microbiome and metagenomic analyses. METHODS: Seven serial C. difficile-positive stool samples were collected as part of an ongoing surveillance system in Texas. Samples, including the index case, represented independent CDI episodes interspersed between four separate FMT procedures between 2016 and 2018. PCR ribotype (RT) testing, 16S rRNA gene sequencing, MIC testing, multidrug-resistant organism (MDRO) screening, and shotgun metagenome sequencing were conducted for each of the samples. RESULTS: The patient was a 42-year-old female with various comorbidities, including systemic lupus erythematosus. She received continuous non-CDI antibiotic courses throughout her CDI therapy for a variety of infections. The vancomycin MICs in infecting C. difficile strains increased with cumulative vancomycin exposure. Multidrug-resistant organisms were detected in stool, including Enterococcus spp., MRSA, and Candida glabrata. The first five of the seven strains were RT 078–126, one was mixed RT 002 and RT 054, and one was RT 002. The analysis of 16S rRNA gene sequences demonstrated that microbial diversity was never restored after FMT procedures. A strong correlation between microbial and functional gene compositions suggests that fecal samples share many microbial species with associated functional genes. CONCLUSION: A number of systems biology changes were observed in a patient with persistent CDI despite multiple FMTs. The lack of FMT engraftment was most likely due to continuous broad-spectrum antibiotic exposure in an immunocompromised patient. DISCLOSURES: All authors: No reported disclosures.