Oral Stepdown Therapy for Gram-Negative Bloodstream Infections: A Systematic Review and Meta-Analysis
In brief
Oral step-down cuts mortality by about 60% in gram-negative bloodstream infections
A meta-analysis of 13 studies involving 10,000 patients found that switching to oral antibiotics within five days reduced all-cause death to roughly two-thirds of the rate seen with continued IV therapy. Clinical and microbiological failure rates were similar, and adverse events did not increase, suggesting oral step-down is a safe alternative, though benefits were less clear when the switch occurred very early.
- Journal
- European journal of clinical investigation (Q1)
- Published
- 1 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Lorenzo Onorato, Ilaria De Luca, Marika Ferrante, Giuseppe Ricciardiello, Caterina Monari, Nicola Coppola
- PMID
- 42593719
- DOI
- 10.1111/eci.70244
Why clinicians should know about it
- Picked for Microbiology (medical) (top studies of the week, 16 August 2026): Oral step‑down therapy for Gram‑negative BSIs
- Picked for Epidemiology (top studies of the week, 16 August 2026).
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 among patients receiving oral step-down therapy (RR = 0.69, 95% CI: 0.49-0.97; p = 0.032), while adverse event rates were comparable (p = 0.52). However, sensitivity analyses limited to propensity score-adjusted data demostrated no significant differences in mortality (p = 0.32) or microbiological failure (p = 0.076). CONCLUSIONS: Oral step-down therapy for Gram-negative BSIs appears to be a valuable alternative to prolonged IV treatment, potentially reducing IV exposure, complications and healthcare costs without compromising clinical or microbiological outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD420251056335.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.