Oral Stepdown Therapy for Gram-Negative Bloodstream Infections: A Systematic Review and Meta-Analysis
Abstract
Background: Early oral step-down has been proposed as a strategy to optimize antimicrobial use in Gram-negative bloodstream infections (BSIs).
Methods: We performed a systematic review and meta-analysis of full-text studies published in English and indexed in MEDLINE and EMBASE up to April 2025. Randomized controlled trials (RCTs) and observational studies including patients with Gram-negative BSIs managed either with oral step-down within 5 days of IV therapy or with continued IV therapy were eligible. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies.
Results: Of 4120 screened records, 13 studies (3 RCTs and 10 cohort studies) including 10,000 patients met the inclusion criteria; 5016 of enrolled patients (52%) switched to oral therapy, mainly to fluoroquinolones (2992, 59.6%). A lower all-cause mortality was observed in patients receiving oral step-down (RR: 0.39, 95% CI: 0.16-0.93; p = 0.034). When stratifying studies according to timing of the switch to oral therapy, no significant difference in mortality was observed in studies with a median switch time ≤ 3 days (p = 0.29). Conversely, studies with a median switch time > 3 days showed a lower mortality rate in the oral step-down group, approaching statistical significance (p = 0.051). No significant differences were found between treatment groups in terms of clinical failure (p = 0.28). Microbiological failure was significantly less frequent…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 10,000 participants or records.
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