Abstract Background Step-down oral antibiotic therapy (SDO) is commonly used to treat uncomplicated gram-negative bacteremia (GNB), but real-world treatment outcomes and risk factors for failure remain unclear. Methods We conducted a retrospective cohort study of hospitalized adults with uncomplicated GNB within a large integrated healthcare system from 2018 to 2022, stratifying patients by antibiotic route: complete course of intravenous antibiotic (CIV) or initial intravenous followed by SDO. The primary outcome was a composite of 90-day all-cause mortality, all-cause readmission, or recurrent GNB. Secondary analysis identified risk factors for adverse outcomes using multivariable Cox regression. Results We included 9,164 patients, of whom 8,263 received SDO and 901 received CIV therapy. All-cause mortality was 1.1% overall, with no significant difference between groups (CIV 1.4% vs. SDO 1.0%, p = 0.3). All-cause readmission and recurrent GNB were more frequent in the CIV group than SDO group (33% vs. 18%, and 5.8% vs. 2.4%, respectively; both p 0.001). A high Charlson Comorbidity Index (CCI) was independently associated with all adverse outcomes in the full cohort and in both treatment groups. Among SDO patients, fluoroquinolones were associated with a lower GNB recurrence rate (1.6%), whereas beta-lactams were linked to a higher recurrence rate (3.2%). Conclusions SDO appears as effective as CIV for treating uncomplicated GNB, with comparable mortality. A high CCI score is a strong predictor of adverse outcomes. Fluoroquinolones remain a favorable SDO option, though further research is warranted to evaluate alternative oral antibiotic agents.
Luo et al. (2026) studied this question.