Effect of Erythromycin on Chronic Respiratory Infection Caused byPseudomonas aeruginosawith Biofilm Formation in an Experimental Murine Model

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. aeruginosaprecoated 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.

Piericidins, Novel Quorum-Sensing Inhibitors against Chromobacterium violaceum CV026, from Streptomyces sp. TOHO-Y209 and TOHO-O348

“…When the concentration of such an excreted metabolite reaches its threshold level, certain types of gene expression resulting in bioluminescence [1], biofilm formation [2,3], swarming motility [4], antibiotic biosynthesis [5,6] virulence factor production [7,8], etc., are triggered by the metabolite (autoinducer). Disruption of the QS system in pathogenic Burkholderia cepacia and B. pseudomallei resulted in reduced pathogenicity in murine and hamster infection [9,10], and erythromycin inhibits biofilm formation of Pseudomonas aeruginosa below the minimum inhibitory concentration (MIC) [11]. Therefore, compounds that inhibit QS have great potential for use in the treatment of bacterial infectious diseases.…”

Recycling of Peptidyl-tRNAs by Peptidyl-tRNA Hydrolase Counteracts Azithromycin-Mediated Effects on Pseudomonas aeruginosa

“…Macrolides were shown to have immunomodulatory activity, which results in a decreased inflammatory response to bacterial stimulation (16), and there have been several studies demonstrating that macrolides inhibit virulence factor production in P. aeruginosa in vitro and in vivo and interfere with biofilm formation (17,18,19,20,21,22).…”

Azithromycin Blocks Quorum Sensing and Alginate Polymer Formation and Increases the Sensitivity to Serum and Stationary-Growth-Phase Killing ofPseudomonas aeruginosaand Attenuates ChronicP. aeruginosaLung Infection inCftr−/−Mice

“…A murine study by Nagata et al (46) that used plastic tubes precoated with P. aeruginosa as a base for the development of a chronic infection has demonstrated that biofilm formation is suppressed by erythromycin. A favorable modulation of the immune response by AZM has been indicated by Moser et al (45) in a mouse model with seaweed alginate-entrapped P. aeruginosa.…”