Tateda Kazuhiro, Ishii Yoshikazu, Kimura Soichiro, Horikawa Manabu, Miyairi Shinichi, Yamaguchi Keizo
Department of Microbiology and Infectious Disease, Toho University School of Medicine, 5-21-16 Ohmorinishi, Ohtaku, Tokyo, 143-8540, Japan.
J Infect Chemother. 2007 Dec;13(6):357-67. doi: 10.1007/s10156-007-0555-2. Epub 2007 Dec 25.
A breakthrough in antibiotic chemotherapy for patients with chronic Pseudomonas aeruginosa pulmonary infections was brought about by findings in a patient with diffuse panbronchiolitis (DPB), who had been treated with erythromycin over a period of years. Recent clinical trials have demonstrated that long-term macrolide therapy can be used not only for DPB patients but also for those with other chronic infections, including patients with cystic fibrosis (CF). The pathogenesis of chronic P. aeruginosa infection is considered to arise from a bacterial cell-to-cell signaling mechanism, named "quorum-sensing", which enables the bacteria to coordinately turn on and off their virulence genes through the production of autoinducer molecules. Accumulating evidence from clinical and basic science fields suggests the potential of macrolides as Pseudomonas quorum-sensing inhibitors. In this review, we briefly summarize the data on the clinical efficacy of macrolides in DPB and CF patients. Then we discuss the mechanisms of action of macrolides from the viewpoint of sub-minimum inhibitory concentration (sub-MIC) macrolide effects on P. aeruginosa, particularly the potential activity of this antibiotic to suppress the bacterial quorum-sensing system.
一名患有弥漫性泛细支气管炎（DPB）的患者多年来接受红霉素治疗，这一病例的发现为慢性铜绿假单胞菌肺部感染患者的抗生素化疗带来了突破。最近的临床试验表明，长期大环内酯类药物治疗不仅可用于DPB患者，也可用于其他慢性感染患者，包括囊性纤维化（CF）患者。慢性铜绿假单胞菌感染的发病机制被认为源于一种名为“群体感应”的细菌细胞间信号传导机制，该机制使细菌能够通过产生自诱导分子来协调其毒力基因的开启和关闭。临床和基础科学领域越来越多的证据表明，大环内酯类药物具有作为铜绿假单胞菌群体感应抑制剂的潜力。在本综述中，我们简要总结了大环内酯类药物对DPB和CF患者临床疗效的数据。然后，我们从低于最低抑菌浓度（sub-MIC）的大环内酯类药物对铜绿假单胞菌的作用角度，特别是该抗生素抑制细菌群体感应系统的潜在活性，来探讨大环内酯类药物的作用机制。
