Kim Kyeongdeok, Lee Jihye
Division of Pulmonology and Allergy, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 31151, Republic of Korea.
J Clin Med. 2025 Sep 4;14(17):6254. doi: 10.3390/jcm14176254.
: 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. : 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 I statistic (I). : We identified four randomized controlled trials (RCTs) ( = 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; I = 0%), whereas observational studies showed a statistically significant mortality reduction associated with macrolide therapy (RR 0.79, 95% CI 0.65-0.95; I = 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. : 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.
脓毒症和脓毒性休克与死亡率显著增加相关。一些研究表明，大环内酯类药物可独立于抗生素作用改善预后，可能是通过免疫调节实现的。本研究旨在确定大环内酯类药物治疗脓毒症和脓毒性休克的有效性。我们检索了电子生物医学数据库，以研究大环内酯类药物治疗与非大环内酯类药物治疗对脓毒症或脓毒性休克患者的影响。主要结局是总体死亡率，还根据脓毒症的主要病因和大环内酯类药物类型对亚组进行了分析。次要结局包括重症监护病房（ICU）住院时间（LOS）和医院住院时间。我们使用随机效应模型计算了合并风险比（RR）和平均差（MD）以及95%置信区间（CIs），并使用I²统计量（I²）评估了统计异质性。我们纳入了四项随机对照试验（RCTs）（n = 1020）和七项观察性研究（n = 2519）。在RCTs中，大环内酯类药物组和对照组的总体死亡率无显著差异（RR 1.08，95% CI 0.92 - 1.27；I² = 0%），而观察性研究显示大环内酯类药物治疗与死亡率显著降低相关（RR 0.79，95% CI 0.65 - 0.95；I² = 49%）。RCTCTs中按大环内酯类药物类型和脓毒症病因进行的亚组分析无显著差异。两组间ICU和医院住院时间无显著差异。基于目前RCTs的证据，辅助使用大环内酯类药物治疗可能不会给脓毒症或脓毒性休克患者带来显著的死亡率获益。需要进一步开展大规模随机试验，以更好地确定大环内酯类药物在脓毒症管理中的作用。
