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Background The gut microbiota is a defense mechanism against colonization of multidrug-resistant organisms (MDROs), including carbapenem-resistant Enterobacteriacae (CRE). Gut dysbiosis caused by broad-spectrum antibiotics favors MDRO colonization and increased susceptibility of intestinal infections, including C. difficile infection (CDI). Increased CDI severity may increase the risk of bacterial translocation due to damage to colonic epithelial layer. The aim of this study was to assess CDI disease severity and subsequent risk for MDRO systemic infection. Methods This was a prospective, observational study of adult hospitalized patients tested for CDI at a large, university-affiliated tertiary care hospital. Patients with a history of systemic MDRO infection in the past 90-days of stool testing were excluded. Patients were stratified by test positivity (CDI vs. antibiotic-associated diarrhea (AAD)), as well as, CDI disease severity and followed for 30-days for subsequent MDRO infections defined as presence of MDRO cultures from systemic, normally sterile sites (blood, urine, cerebrospinal fluid). Stool samples were collected and grown for MDRO colonization. Results A total of 335 CDI-positive and 135 antibiotic-associated diarrhea (AAD) hospitalized patients were included. No differences were found in rates of MDRO colonization by test positivity or disease severity (overall 68% VRE, 53% Candida spp., 30.4% MRSA, and 1.8% CRE). Significantly more patients with severe CDI had higher rates of developing systemic MDROs compared with mild-moderate CDI and AAD (23.2%, n = 112 vs. 8.1%, n = 223 P &lt; 0.001; vs. 11.9%, p = 0.018). Severe CDI was found to be an independent risk factor for subsequent systemic MDRO infection via logistic regression. Conclusion Severe CDI disease is associated with an increased risk of systemic MDRO infections. Disclosures All authors: No reported disclosures.

2391. Increased Risk of Systemic Infections with Multidrug-Resistant Organisms in Patients with Severe Clostridioides difficile Infection