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Background Fluoroquinolone (FQ) prophylaxis for high-risk neutropenic patients has been shown to reduce rates of febrile neutropenia and is standard at many centers. For patients who cannot receive a FQ, oral third-generation cephalosporins (OTGCs) are often used as an alternative; however, this strategy is not well studied. We sought to compare clinically-relevant outcomes in patients receiving FQ vs. OTGC prophylaxis. Methods This was a retrospective cohort study of adults who were admitted to the Malignant Hematology service at the University of California, San Francisco between December 2012 and June 2018 and received >48 hours of an OTGC (cefdinir or cefpodoxime) or an FQ (levofloxacin) for neutropenic prophylaxis. For each OTGC patient, an FQ patient was randomly selected from the same admission year. Exclusion criteria were fever on admission, receipt of systemic antibiotics prior to or during the prophylaxis period, diagnosis of acute promyelocytic leukemia, and crossover. A multivariable logistic regression analysis adjusting for age, QTc, Charlson Comorbidity Index, underlying diagnosis, receipt of stem cell transplant (SCT), and duration of neutropenia was used to compare the groups with respect to a primary composite outcome of 30-day in-hospital mortality, intensive care unit (ICU) admission, and bacteremia. Results Of 520 patients screened, 173 (33.3%) were included in the study; 76 of these received an OTGC and 97 received an FQ. Hematologic diagnoses included multiple myeloma (38.2%), acute myeloid leukemia (29.5%), acute lymphoblastic leukemia (8.7%), B-cell lymphoma (12.7%), aplastic anemia (2.9%), and others (3.5%). During admission, 9.2% underwent allogeneic SCT and 28.3% underwent autologous SCT. Outcomes are shown in Table 1. Conclusion Prophylaxis with an OTGC rather than a FQ was not associated with worse outcomes in this pragmatic evaluation of a heterogeneous group of patients with hematologic malignancies. In this multivariable model, neutropenia lasting more than 7 days was the only consistent predictor of failure across outcomes, suggesting that degree of immunosuppression is a much more significant driver of poor outcomes in this population than is prophylaxis choice. Further evaluation of the role of prophylaxis is needed. Disclosures All authors: No reported disclosures.

2685. Oral Third-Generation Cephalosporins vs. Levofloxacin for Antibacterial Prophylaxis in Neutropenic Patients with Hematologic Malignancies