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

Background: Beta 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.

Methods: This 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.

Results: A 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.

Conclusion: Cefprozil 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.