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Abstract Background Hospital-onset C. difficile infection (HO-CDI) has been problematic at our hospital, with rates almost 50% greater than predicted. C. difficile whole-genome sequencing (WGS) data were used to define the transmission pattern, followed by a diagnostic stewardship intervention. Methods Isolates from CDI cases were sequenced for strain relatedness and epidemiologically analyzed using a single nucleotide polymorphism (SNP)-based approach. In June 2017, a diagnostic stewardship intervention began which included provider education and a weekday review of CDI orders placed after hospital day 3 for the following indications: >3 stools/24 hours, the absence of laxative administration, the presence of fever/leukocytosis or a history of inflammatory bowel disease. In November 2017, an EMR-based testing algorithm was introduced to supplement the review process. Orders not meeting testing criteria were discussed with the ordering provider, with a suggestion to cancel orders without appropriate indications. Results WGS assigned 36 isolates to 19 different multi-locus sequence types (ST), including five assigned to ST-1, a sequence that encompasses the ribotype 027 clade (Figure 1). SNP-based analysis indicated closely related, but non-identical strains, inconsistent with nosocomial transmission. Six hundred forty-six CDI orders were reviewed, of which 421 (65%) met criteria and 64 (15%) were positive. Two hundred twenty-five (35%) of orders were recommended for cancellation. The HO-CDI rate decreased from 11.67/10k in the 5-month baseline period to 7.13/10k in the 9-month intervention period (P = 0.0008) (Figure 2). Conclusion WGS revealed that nosocomial transmission of C. difficile was an unlikely cause for our elevated CO-CDI rate. A diagnostic stewardship intervention which focused on identifying community-acquired infection and avoiding over-testing was associated with a sustained decrease in the HO-CDI rate which has persisted for 9 months. Figure 1. Figure 2. Disclosures All authors: No reported disclosures.

523. Use of Whole-Genome Sequencing to Guide a C. difficile Diagnostic Stewardship Program