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

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 > 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 < .0001) and high-risk antibiotics (OR = 1.639, 95% CI: 1.45–1.85, P < .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 < .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.