Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model
Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model
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DOI：
10.1128/aac.48.6.2251-2259.2004
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发表时间：
2004-06
影响因子：
4.9
通讯作者：
T. Nagata;H. Mukae;J. Kadota;Tomayoshi Hayashi;T. Fujii;M. Kuroki;R. Shirai;K. Yanagihara;K. Tomono;T. Koji;S. Kohno
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文献类型：
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作者：
T. Nagata;H. Mukae;J. Kadota;Tomayoshi Hayashi;T. Fujii;M. Kuroki;R. Shirai;K. Yanagihara;K. Tomono;T. Koji;S. Kohno
摘要：弥漫性全细支气管炎（DPB）是一种慢性下呼吸道感染，通常与持续性晚期铜绿假单胞菌感染相关。然而，某些大环内酯类药物的低剂量长期治疗对大多数 DPB 患者有效。本研究旨在通过使用我们建立的慢性呼吸道铜绿假单胞菌感染小鼠模型来检查长期红霉素（ERY）治疗的效果。从用铜绿假单胞菌预涂管插管后的第80天开始，在随后的10、20、40和80天中施用ERY或盐水。对小鼠肺部进行细菌学和组织学分析，并对插管进行电子显微镜检查。在小鼠模型中，ERY 治疗 80 天显着减少了肺部存活的铜绿假单胞菌数量（P < 0.05）。 ERY处理80天后，放入小鼠支气管的接种管内壁上由铜绿假单胞菌原位形成的生物膜明显变薄。我们的结论是，大环内酯类药物在 DPB 中的临床疗效可能至少部分归因于铜绿假单胞菌生物膜形成的减少。
ABSTRACT Diffuse panbronchiolitis (DPB) is a chronic lower respiratory tract infection commonly associated with persistent late-stage Pseudomonas aeruginosa infection. However, low-dose long-term therapy with certain macrolides is effective in most patients with DPB. The present study was designed to examine the effects of long-term erythromycin (ERY) therapy by using our established murine model of chronic respiratory P. aeruginosa infection. ERY or saline was administered from day 80 after intubation with a P. aeruginosa-precoated tube for the subsequent 10, 20, 40, and 80 days. Bacteriologic and histologic analyses of the murine lungs and electron microscopy of the intubated tube were performed. In the murine model, treatment with ERY for 80 days significantly reduced the number of viable P. aeruginosa organisms in the lungs (P < 0.05). The biofilm formed in situ by P. aeruginosa on the inner wall of the inoculation tube placed into the murine bronchus became significantly thinner after 80 days of ERY treatment. We conclude that the clinical efficacy of macrolides in DPB may be due at least in part to the reduction in P. aeruginosa biofilm formation.