Giamarellos-Bourboulis Evangelos J, Baziaka Fotini, Antonopoulou Anastasia, Koutoukas Pantelis, Kousoulas Vassilios, Sabracos Lambros, Panagou Charalambos, Perrea Despina, Giamarellou Helen
4th Department of Internal Medicine, University of Athens, Medical School, Greece.
Int J Antimicrob Agents. 2005 Feb;25(2):168-72. doi: 10.1016/j.ijantimicag.2004.08.018.
To assess the efficacy of clarithromycin as an immunomodulator in experimental sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFalpha and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFalpha and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of sepsis since its efficacy was proved after administration on presentation of sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative sepsis.
为评估克拉霉素作为免疫调节剂在大肠杆菌所致实验性脓毒症中的疗效，对40只家兔行右侧输尿管结扎并向肾盂内注射受试分离菌株后诱发急性肾盂肾炎。在脓毒症相关性肺水肿出现时进行如下四组治疗：A组：对照组；B组：克拉霉素组；C组：阿米卡星组；D组：两种药物联合组。记录生存率，并测定血清内毒素（LPS）、肿瘤坏死因子-α（TNFα）、丙二醛（MDA）水平及细菌计数。A、B、C、D四组的平均生存时间分别为2.51天、7.60天、10.25天和11.40天。A组血清TNFα和MDA水平随时间升高。细菌攻击后6小时出现的肺水肿伴有TNFα和MDA升高；给予克拉霉素可降低其值。结论是静脉注射克拉霉素可能是一种有前景的用于脓毒症治疗的免疫调节药物，因为在脓毒症相关性肺水肿出现时给予该药已证明其疗效。本研究结果强调了对克拉霉素用于革兰阴性菌脓毒症治疗进行进一步临床研究的必要性。
