Simonis Fabienne D, de Iudicibus Gianfranco, Cremer Olaf L, Ong David S Y, van der Poll Tom, Bos Lieuwe D, Schultz Marcus J
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.
Laboratory for Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center, Amsterdam, The Netherlands.
Ann Transl Med. 2018 Jan;6(2):24. doi: 10.21037/atm.2017.12.25.
Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS).
This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers.
In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1-4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43-0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% 32.9%; OR, 0.62 (interquartile range, 0.39-0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS pulmonary ARDS and also varied by biological phenotype.
These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS.
大环内酯类药物在各种炎症性疾病状态下具有良好的免疫调节作用。我们研究了大环内酯类药物治疗与急性呼吸窘迫综合征（ARDS）患者死亡率之间的关联。
这是一项对荷兰两家大学附属医院重症监护病房（ICU）中危重症患者进行的大型前瞻性观察性研究中ARDS患者的非计划二次分析。感兴趣的暴露因素是因非感染原因使用低剂量大环内酯类药物；我们排除了因感染而接受高剂量大环内酯类药物治疗的患者。主要终点是30天死亡率。在整个队列以及倾向评分匹配队列中确定大环内酯类药物治疗与死亡率之间的关联；比较了肺源性ARDS与非肺源性ARDS之间以及基于20种生物标志物血浆水平的两种生物学表型之间的关联。
总共分析了873例ARDS患者，其中158例（18%）在ICU住院期间接受了大环内酯类药物治疗，中位治疗时间为3天（四分位间距，1 - 4天）。红霉素是最常处方的大环内酯类药物（97%）。大环内酯类药物治疗与整个队列中30天死亡率降低相关[22.8%对31.6%；粗比值比（OR），0.64（四分位间距，0.43 - 0.96），P = 0.03]。倾向评分匹配队列中的关联仍然显著[22.8%对32.9%；OR，0.62（四分位间距，0.39 - 0.96），P = 0.03]。非肺源性ARDS与肺源性ARDS患者中倾向匹配的死亡率关联不同，并且也因生物学表型而异。
这些数据共同表明，因非感染原因使用低剂量大环内酯类药物治疗与ARDS患者死亡率降低相关。
