Oral Step-Down for Gram-Negative Bacteremia Survives Confounding Adjustment
This meta-analysis synthesizes 13 studies to clarify whether early oral step-down in Gram-negative bloodstream infections preserves clinical and microbiological outcomes, and how much of the apparent mortality benefit is confounding by indication.
Oral antibiotics may safely replace IVs for Gram-negative BSIs.
Optimizing antimicrobial use in Gram-negative bloodstream infections (BSIs) can reduce complications and healthcare costs. Oral step-down therapy showed lower all-cause mortality (RR: 0.39) and less microbiological failure (RR: 0.69) compared to continued intravenous (IV) therapy. The findings support switching to oral antibiotics within 5 days for certain patients with Gram-negative BSIs, though differences were not significant in rigorous sensitivity analyses. Oral step-down therapy for Gram-negative BSIs is effective and reduces IV exposure without worsening outcomes.
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Authors:Onorato L, De Luca I, Ferrante M, Ricciardiello G, Monari C, Coppola N
Citation:Onorato L, De Luca I, Ferrante M, et al. Oral Stepdown Therapy for Gram-Negative Bloodstream Infections: A Systematic Review and Meta-Analysis. European journal of clinical investigation. 2026;56(8):e70244. doi:10.1111/eci.70244
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Executive Summary
Study Design
Patient Population
Primary Outcomes
Secondary Outcomes & Safety Profile
Pharmacist Implications
Clinical Pearls
Limitations
Controversies & Evidence Gaps
Cost & Logistics
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