Fraunhofer Institute for Molecular Biology and Applied Ecology, Project Group Translational Medicine and Pharmacology, Frankfurt am Main, Germany; Institute of Pharmacology for Life Scientists, Goethe University Frankfurt, Frankfurt am Main, Germany; Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Fidelta d.o.o., Zagreb, Croatia.
Pharmacol Ther. 2014 Aug;143(2):225-45. doi: 10.1016/j.pharmthera.2014.03.003. Epub 2014 Mar 11.
Azithromycin is a macrolide antibiotic which inhibits bacterial protein synthesis, quorum-sensing and reduces the formation of biofilm. Accumulating effectively in cells, particularly phagocytes, it is delivered in high concentrations to sites of infection, as reflected in rapid plasma clearance and extensive tissue distribution. Azithromycin is indicated for respiratory, urogenital, dermal and other bacterial infections, and exerts immunomodulatory effects in chronic inflammatory disorders, including diffuse panbronchiolitis, post-transplant bronchiolitis and rosacea. Modulation of host responses facilitates its long-term therapeutic benefit in cystic fibrosis, non-cystic fibrosis bronchiectasis, exacerbations of chronic obstructive pulmonary disease (COPD) and non-eosinophilic asthma. Initial, stimulatory effects of azithromycin on immune and epithelial cells, involving interactions with phospholipids and Erk1/2, are followed by later modulation of transcription factors AP-1, NFκB, inflammatory cytokine and mucin release. Delayed inhibitory effects on cell function and high lysosomal accumulation accompany disruption of protein and intracellular lipid transport, regulation of surface receptor expression, of macrophage phenotype and autophagy. These later changes underlie many immunomodulatory effects of azithromycin, contributing to resolution of acute infections and reduction of exacerbations in chronic airway diseases. A sub-group of post-transplant bronchiolitis patients appears to be sensitive to azithromycin, as may be patients with severe sepsis. Other promising indications include chronic prostatitis and periodontitis, but weak activity in malaria is unlikely to prove crucial. Long-term administration of azithromycin must be balanced against the potential for increased bacterial resistance. Azithromycin has a very good record of safety, but recent reports indicate rare cases of cardiac torsades des pointes in patients at risk.
阿奇霉素是一种大环内酯类抗生素，可抑制细菌蛋白质合成、群体感应并减少生物膜形成。阿奇霉素在细胞内（尤其是吞噬细胞）积聚，在体内迅速清除和广泛分布，使药物在感染部位达到高浓度。阿奇霉素适用于呼吸道、泌尿生殖道、皮肤和其他细菌感染，并对慢性炎症性疾病（包括弥漫性泛细支气管炎、移植后细支气管炎和酒渣鼻）具有免疫调节作用。宿主反应的调节促进了其在囊性纤维化、非囊性纤维化支气管扩张、慢性阻塞性肺疾病（COPD）和非嗜酸性哮喘中的长期治疗获益。阿奇霉素对免疫和上皮细胞的初始刺激作用，涉及与磷脂和 Erk1/2 的相互作用，随后是转录因子 AP-1、NFκB、炎症细胞因子和粘蛋白释放的后期调节。细胞功能的延迟抑制作用和高溶酶体积累伴随着蛋白质和细胞内脂质转运的破坏、表面受体表达、巨噬细胞表型和自噬的调节。这些后期变化是阿奇霉素许多免疫调节作用的基础，有助于急性感染的消退和慢性气道疾病加重的减少。亚组移植后细支气管炎患者似乎对阿奇霉素敏感，严重败血症患者也可能如此。其他有前途的适应症包括慢性前列腺炎和牙周炎，但疟疾的弱活性不太可能证明是关键。长期使用阿奇霉素必须与细菌耐药性增加的潜在风险相平衡。阿奇霉素具有非常好的安全性记录，但最近的报告表明，有风险的患者中罕见出现尖端扭转型室性心动过速。
