Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection: A Systematic Review and Noninferiority Meta-Analysis.

Summary

Pooling four RCTs (n=3,729 ITT), 7 days of antibiotics for Gram-negative bloodstream infections had a 90-day mortality risk ratio of 0.91 (95% CrI, 0.69–1.22) vs 14 days, with a 97.8% probability of noninferiority (margin 1.25). Results were consistent in per-protocol analyses.

Key Findings

• Four RCTs (n=3,729 ITT) comparing 7 vs 14 days showed 90-day mortality RR 0.91 (95% CrI, 0.69–1.22) with 97.8% probability of noninferiority.
• Per-protocol analyses (n=3,126) yielded RR 0.93 (95% CrI, 0.68–1.32) with 95.1% noninferiority probability.
• Trials included adults with Gram-negative bloodstream infections and adequate source control.
• Bayesian random-effects models with prespecified NI margin (1.25) and PRISMA-conformant methods were used.

Clinical Implications

For adults with Gram-negative bacteremia and adequate source control, clinicians can consider 7-day therapy, aligning with stewardship goals while maintaining outcomes.

Limitations

• Generalizability limited to patients similar to included RCTs (adequate source control, clinical stability criteria).
• Noninferiority conclusions depend on the chosen margin and heterogeneity assumptions.

Future Directions

Define subgroups (e.g., immunocompromise, deep foci) where shorter courses may or may not apply; evaluate patient-centered outcomes and resistance emergence.