Efficacy of a transition to oral antimicrobial therapy for gram-negative bacilli bloodstream infection: systematic review and meta-analysis.

Abstract

Background: While the disease and economic impact of gram-negative bacilli bloodstream infections (GNB-BSI) are high, treatment strategies, including transitioning from intravenous antimicrobial therapy (IVAT) to oral stepdown antimicrobial therapy (OSAT) are still in their nascent stage of development.

Methods: A systematic review and meta-analysis evaluated the clinical effectiveness of OSAT compared with IVAT for GNB-BSI. Medline and Embase were searched from January 1980 to March 2025, along with the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and reference lists of eligible studies. Randomized controlled trials and observational studies comparing OSAT with IVAT were included. Three investigators screened studies, extracted data, assessed study quality, and risk of bias, following PRISMA guidelines, ROBINS-E for observational studies and RoB 2 for randomized trials. Certainty of evidence was assessed using the GRADE framework.

Results: Sixteen studies involving 4,858 patients who received OSAT and 4,961 patients who received IVAT were extracted for review. The pooled risk ratio for mortality and treatment failure in the primary analysis which included studies adjusting for confounders (n = 3) was 0.95 (95% confidence interval [CI]: 0.42, 2.14; I ² = 8%) and 1.11 (95% CI: 0.22, 5.51; I ² = 59%), respectively. The GRADE assessment for the primary analyses rated the evidence as very low to moderate certainty. Outcome definitions varied substantially across studies, potentially affecting pooled estimates.

Conclusions: Although an imbalance in the baseline characteristics of patients with GNB-BSI across the studies warranted closer attention, OSAT may be as effective as IVAT for GNB-BSI without compromising clinical outcomes. Nevertheless, high-quality RCTs are needed before making definitive recommendations.