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.

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阿奇霉素：作用机理及其与临床应用的相关性。

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的形成。它在细胞特别是吞噬细胞中有效积累，并以高浓度传递到感染部位，这体现在快速血浆清除和广泛的组织分布中。阿奇霉素适用于呼吸道，泌尿生殖器，皮肤和其他细菌感染，并在慢性炎症中发挥免疫调节作用，包括弥漫性全细支气管炎，移植后细支气管炎和酒渣鼻。宿主反应的调节促进其在囊性纤维化，非囊性纤维化支气管扩张，慢性阻塞性肺疾病（COPD）恶化和非嗜酸性哮喘中的长期治疗益处。初始，阿奇霉素对免疫细胞和上皮细胞的刺激作用，包括与磷脂和Erk1 / 2的相互作用，随后对转录因子AP-1，NFκB，炎性细胞因子和粘蛋白的释放进行调节。对细胞功能和高溶酶体积累的延迟抑制作用伴随蛋白质和细胞内脂质运输的破坏，表面受体表达的调节，巨噬细胞表型和自噬。这些后来的变化是阿奇霉素具有许多免疫调节作用的基础，有助于缓解急性感染并减轻慢性气道疾病的恶化。移植后细支气管炎患者的亚组似乎对阿奇霉素敏感，严重脓毒症患者也可能如此。其他有希望的适应症包括慢性前列腺炎和牙周炎，但是，疟疾活动减弱似乎不太重要。长期服用阿奇霉素必须与增加细菌抵抗力的潜力保持平衡。阿奇霉素具有很好的安全性记录，但最近的报道表明，有风险的患者中很少有心脏尖端扭转型室速的病例。