Macrolide Therapy in Patients with Sepsis or Septic Shock: A Systematic Review and Meta-Analysis

Background: Sepsis and septic shock are associated with markedly increased mortality. Some studies have suggested that macrolides improve outcomes independent of the antibiotic effects, possibly through immunomodulation. This study aimed to determine the effectiveness of macrolides in treating sepsis and septic shock. Methods: We searched electronic biomedical databases to investigate the effects of macrolide therapy versus non-macrolide therapy in patients with sepsis or septic shock. The primary outcome was overall mortality, which was also analyzed across subgroups according to the primary cause of sepsis and type of macrolides. Secondary outcomes consisted of the intensive care unit (ICU) length of stay (LOS) and hospital LOS. We calculated pooled risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs) using a random-effects model, and statistical heterogeneity was assessed with the I² statistic (I²). Results: We identified four randomized controlled trials (RCTs) (n = 1020) and seven observational studies (n = 2519). In RCTs, there was no significant difference in overall mortality between the macrolide and control groups (RR 1.08, 95% CI 0.92-1.27; I² = 0%), whereas observational studies showed a statistically significant mortality reduction associated with macrolide therapy (RR 0.79, 95% CI 0.65-0.95; I² = 49%). Subgroup analyses by macrolide type and sepsis cause in RCTs showed no significant differences. ICU and hospital LOS showed no significant differences between groups. Conclusions: Based on the current evidence from RCTs, adjunctive macrolide therapy may not provide a significant mortality benefit in patients with sepsis or septic shock. Further large-scale randomized trials are needed to better establish the role of macrolides in sepsis management.