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Antimicrobial Agents and Chemotherapy, June 2004, p. 2251-2259, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2251-2259.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Effect of Erythromycin on Chronic Respiratory Infection Caused by Pseudomonas aeruginosa with Biofilm Formation in an Experimental Murine Model

Towako Nagata,1 Hiroshi Mukae,1* Junichi Kadota,2 Tomayoshi Hayashi,3 Takeshi Fujii,1 Misuzu Kuroki,1 Ryo Shirai,1 Katsunori Yanagihara,1 Kazunori Tomono,1 Takehiko Koji,4 and Shigeru Kohno1

Second Department of Internal Medicine,1 Department of Histology and Cell Biology, School of Medicine, Nagasaki University,4 Department of Pathology, Nagasaki University Hospital, Nagasaki,3 Second Department of Internal Medicine, Medical School, Oita University, Oita, Japan2

Received 17 August 2003/ Returned for modification 31 October 2003/ Accepted 17 February 2004

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.

* Corresponding author. Mailing address: Second Department of Internal Medicine, School of Medicine, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852, Japan. Phone: 81 (95)-849-7278. Fax: 81 (95)-849-7285. E-mail: hmukae{at}net.nagasaki-u.ac.jp.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2251-2259, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2251-2259.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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