Giamarellos-Bourboulis Evangelos J, Pechère Jean-Claude, Routsi Christina, Plachouras Diamantis, Kollias Spyridon, Raftogiannis Maria, Zervakis Dimitrios, Baziaka Fotini, Koronaios Apostolos, Antonopoulou Anastasia, Markaki Vassiliki, Koutoukas Pantelis, Papadomichelakis Evangelos, Tsaganos Thomas, Armaganidis Apostolos, Koussoulas Vassilios, Kotanidou Anastasia, Roussos Charis, Giamarellou Helen
Fourth Department of Internal Medicine, University of Athens Medical School, Athens, Greece.
Clin Infect Dis. 2008 Apr 15;46(8):1157-64. doi: 10.1086/529439.
Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP).
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.
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).
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.
由于克拉霉素在实验研究中显示出有益的非抗生素作用，因此对其在脓毒症和呼吸机相关性肺炎（VAP）患者中的疗效进行了测试。
2004年6月至2005年11月，200例脓毒症和VAP患者被纳入一项双盲、随机、多中心试验。100例患者连续3天每天静脉注射1克克拉霉素；另外100例患者接受安慰剂治疗。主要结局指标为VAP的缓解情况、机械通气时间以及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、病原体以及所用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，安慰剂治疗组和克拉霉素治疗组VAP缓解的中位时间分别为15.5天和10.0天（P = 0.011）；脱机的中位时间分别为22.5天和16.0天（P = 0.049）。对所有入组患者的分析显示，与安慰剂治疗组相比，克拉霉素治疗组患者的临床肺部感染评分下降更快，多器官功能障碍出现延迟（P = 0.047）。在45例死于脓毒症的患者中，克拉霉素治疗组患者的死亡时间比安慰剂治疗组显著延长（P = 0.004）。安慰剂治疗组和克拉霉素治疗组分别有0%和3%的患者出现严重不良事件（P = 0.25）。
克拉霉素可加速存活患者VAP的缓解和脱机，并延迟死于脓毒症患者的死亡时间。28天死亡率未改变。结果令人鼓舞，为脓毒症和VAP的治疗带来了新的视角。
