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Background The association between antibiotic exposure (AE) and healthcare-associated Clostridiodes difficile infection (HA-CDI) has been mostly quantified using cumulative AE as the predictor. However, patients receive similar durations of antibiotics in a variety of ways. We examine the relationship between HA-CDI and other dimensions of AE. Methods Retrospective cohort study was conducted with pediatric and adult inpatients at three New York City hospitals between 2011- 2016 who were prescribed at least one dose of antibiotic, excluding those used to treat CDI. Patient data were collected until the first diagnosis of HA-CDI (a positive CDI test &gt; 3 days after admission), or alternatively at the end of the study period. Four dimensions of AE were calculated: 1) duration – cumulative total calendar days of antibiotics use, 2) discontinuity – the number of separate antibiotic courses that contributed to the duration (a course defined as antibiotics given over ≥ 2 consecutive calendar days separated by at least 24 hours), (3) antibiotic free days – days without antibiotic use, and (4) use of ‘high-risk’ antibiotics – use of antibiotics known for increasing C. difficile risk. We measured the association between each AE dimension and HA-CDI, mutually controlling for each dimension, in a multivariable logistic regression model adjusted for age, sex, comorbidities (e.g., malignancy, transplant status), length of hospitalization, and use of proton pump inhibitors (PPI). Results Of 227,967 hospitalized patients, 104,705 (45.9%) received antibiotics and 1,618 had HA-CDI. In regression analysis, adjusted for cumulative duration, discontinuous antibiotic therapy (OR = 2.02, 95% CI: 1.49–2.74, P &lt; .0001) and high-risk antibiotics (OR = 1.639, 95% CI: 1.45–1.85, P &lt; .0001) both increased HA-CDI risk. A longer antibiotic free interval between courses decreased HA-CDI risk (OR = 0.998, 95% CI: 0.997–0.998, P &lt; .0001). In addition, both PPI use and being immunocompromised were significantly associated with HA-CDI. Conclusion Multiple dimensions of AE in addition to cumulative duration were collectively associated with CDI risk. This has implications for designing accurate CDI prediction models implementing antibiotic stewardship interventions. Disclosures All authors: No reported disclosures.

2393. Dimensions of Cumulative Antibiotic Exposure and Risk of Hospital Onset Clostridiodes Difficile