Reducing antibiotic burden in gram-negative bacteraemia: duration optimization and early oral transition

Gram-negative bloodstream infections have traditionally been managed with prolonged and intravenous antibiotic therapy. This review aims to summarize the evidence supporting strategies to reduce antibiotic burden through shorter treatment durations and/or oral step-down therapy.

Recent randomized controlled trials, target trial emulations, and large observational studies demonstrate that in patients with uncomplicated Gram-negative bloodstream infections an early oral step-down therapy and/or reduced antibiotic courses achieve clinical outcomes comparable to prolonged intravenous therapy and longer treatment durations. Fluoroquinolones and trimethoprim-sulfamethoxazole remain the preferred oral agents because of their high bioavailability. Appropriately dosed oral β-lactams appear to provide comparable outcomes, highlighting the importance of exposure optimization rather than antibiotic class alone. The evidence is expanding also for special populations, but important knowledge gaps remain for patients with severe immunosuppression and multidrug-resistant pathogens.

Current evidence supports reducing antibiotic exposure in selected patients with Gram-negative bloodstream infections by combining shorter treatment durations and early oral step-down therapy. Future studies should address remaining evidence gaps, particularly in frail patients.