Oral Stepdown Therapy for Gram-Negative Bloodstream Infections: A Systematic Review and Meta-Analysis

Area of Science:

• Infectious Diseases
• Pharmacology
• Clinical Medicine

Background:

• Optimizing antimicrobial use is crucial for Gram-negative bloodstream infections (BSIs).
• Early oral step-down therapy is a proposed strategy to enhance antimicrobial stewardship.

Purpose of the Study:

• To systematically review and meta-analyze the efficacy and safety of early oral step-down therapy for Gram-negative BSIs.
• To compare oral step-down therapy with continued intravenous (IV) therapy in patients with Gram-negative BSIs.

Main Methods:

• Systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies.
• Searched MEDLINE and EMBASE databases up to April 2025.
• Assessed risk of bias using standard tools for RCTs and observational studies.

Main Results:

• 13 studies including 10,000 patients met inclusion criteria; 52% switched to oral therapy.
• Oral step-down was associated with lower all-cause mortality (RR: 0.39, p=0.034) and significantly less microbiological failure (RR=0.69, p=0.032).
• No significant differences in clinical failure or adverse events; sensitivity analyses showed no significant differences in mortality or microbiological failure.

Conclusions:

• Oral step-down therapy is a viable alternative to prolonged IV treatment for Gram-negative BSIs.
• This approach may reduce IV exposure, complications, and healthcare costs.
• Clinical and microbiological outcomes are not compromised by early oral step-down therapy.