258. A Comparison of Cefprozil and Fluoroquinolones for Gram-Negative Bacteremia

Abstract

BackgroundBeta lactams and fluoroquinolones (FQ) have been evaluated as step-down therapy options for Gram-negative bacteremia (GNB), but the preferred oral step-down antibiotic remains unclear.MethodsThis retrospective, non-inferiority, cohort study included adult patients who received oral step-down therapy with cefprozil or FQ (ciprofloxacin, levofloxacin) for GNB caused by Proteus spp, Klebsiella spp, or E. coli at SSM Health St. Louis between 1/1/2016 and 2/28/2020. The primary outcome was treatment failure, defined as all-cause mortality or recurrent infection within 30 days of initial bacteremia episode. Assuming an 85% success rate, to achieve 80% power with a noninferiority margin of 15%, 71 patients were required in each arm. Multivariate logistic regression was used to evaluate factors for treatment failure. Factors evaluated for inclusion in the multivariate model were oral antibiotic, age >65 years, urinary source, Pitt bacteremia score >2, ICU admission, and IV antibiotics for >5 days prior to step-down.ResultsA total of 174 patients were included— 103 received cefprozil and 71 received FQ. Most baseline characteristics were similar between groups. Patients in the cefprozil group had more ICU admissions (21.3% vs. 7%; p=0.01), had a higher mean Pitt bacteremia score (1.6 vs 0.7; p< 0.001), and received a longer duration (days) of IV antibiotics prior to step-down therapy (5.2 vs 4.1; p< 0.001). Mean total treatment duration (days) was similar between groups (13.1 vs 13.2; p=0.75). Cefprozil 500 mg PO BID was administered in 84.5% of cefprozil patients. Treatment failure occurred in 3.88% (4/103) of cefprozil patients compared to 1.41% (1/71) of FQ patients (mean difference -2.47%; 95% CI -7.52% to 2.58%). The rate of adverse drug reactions was significantly higher in the FQ arm (2.9% vs 12.6%; p=0.016). In the univariate model, E. coli bacteremia, Pitt bacteremia score >2, and IV antibiotic duration >5 days met pre-defined criteria (p< 0.2) for inclusion in the multivariate model. In the multivariate analysis, these factors were not found to be significant.ConclusionCefprozil was non-inferior to FQ in regard to treatment failure. Cefprozil is an efficacious alternative to FQ for oral step-down treatment of GNB and was associated with significantly fewer adverse effects.Disclosures All Authors: No reported disclosures