Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia
Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia
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DOI：
10.1086/529439
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发表时间：
2008-04-15
影响因子：
11.8
通讯作者：
Giamarellou, Helen
中科院分区：
文献类型：
--
作者：
Giamarellos-Bourboulis, Evangelos J.;Pechere, Jean-Claude;Giamarellou, Helen
背景由于克拉霉素在实验研究中提供了有益的非抗生素效应，因此在脓毒症和呼吸机相关性肺炎（VAP）患者中检测了其疗效。2004年6月至2005年11月，200例脓毒症和VAP患者入组了一项双盲、随机、多中心试验。100例患者静脉注射克拉霉素（1 g），每日1次，连续3天;另100例患者接受安慰剂治疗。主要观察指标为呼吸机相关性肺炎的缓解率、机械通气时间和28天内脓毒症相关死亡率。两组在人口统计学特征、疾病严重程度、病原体和给予的抗菌药物的充分性方面匹配良好。对141例存活患者的分析显示，安慰剂组和克拉霉素组VAP缓解的中位时间分别为15.5天和10.0天（P = 0.011）;脱离机械通气的中位时间分别为22.5天和16.0天（P = 0.049）。包括所有入组患者的分析显示，与安慰剂治疗患者相比，克拉霉素治疗患者的临床肺部感染评分下降更快，多器官功能障碍的出现延迟（P = 0.047）。在45例死于败血症的患者中，克拉霉素治疗组的至死亡时间显著长于安慰剂治疗组（P = .004）。安慰剂组和克拉霉素组的严重不良事件发生率分别为0%和3%（P = 0.25）。克拉霉素可加速存活患者VAP的消退和机械通气的撤机，并延迟死于败血症的患者的死亡。第28天的死亡率没有改变。结果是令人鼓舞的，并提出新的观点败血症和VAP的管理。
Background. Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP).Methods. Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days.Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo-and clarithromycin-treated patients, respectively (P = .011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P = .049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P = .047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P = .004). Serious adverse events were observed in 0% and 3% of placebo-and clarithromycin-treated patients, respectively (P = .25).Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VAP.