Long term effect of erythromycin therapy in patients with chronic Pseudomonas aeruginosa infection.

Abstract

Background -Diffuse panbronchiolitis is a chronic infection ofthe lower respiratory tract common among the Japanese people, with a persistent Pseudomonas aeruginosa infection in the late stage and sustained neutrophil retention in the airways. The long term effect of erythromycin was examined retrospectively in a group of patients with diffuse panbronchiolitis, with and without P aeruginosa infection, and the relationship between drug-induced bacterial clearance and clinical improvement was investigated. Methods -The history, daily volume of sputum, type of organisms in sputum cultures, pulmonary function tests, arterial blood gas tensions, and chest radiographs were compared in 16 patients with diffuse panbronchiolitis with P aeruginosa infection and 12 without. The total and differential cell counts in the bronchoalveolar lavage (BAL) fluid were compared in 14 ofthe 28 patients (five ofwhom were infected with P aeruginosa) before and after 1-12 months of treatment with erythromycin (600 mg/day). The outcome oftreatment in patients showing clearance of organisms on repeated sputum cultures was compared with that in those demonstrating persistence of bacteria in the sputum and patients with normal flora. Results -Erythromycin improved respiratory function and arterial blood gas tensions irrespective of the presence or absence of P aeruginosa in the sputum.Treatment also resulted in a reduction in the BAL fluid total cell count and the percentage of neutrophils in both groups of patients. There were no differences between patients in whom the bacteria cleared and those with persistent bacteria or patients with a normal flora with regard to the degree of improvement of respiratory function, arterial blood gas tensions, and BAL fluid cell composition.Conclusion -The results suggest that the efficacy of erythromycin in diffuse panbronchiolitis may be due to an anti-inflammatory effect, independent of P aeruginosa infection or bacterial clearance.

Quorum sensing in bacterial virulence

“…Subinhibitory concentrations of macrolides have been shown to be effective in inhibiting quorum-sensingdependent virulence both in vivo and in vitro (Imamura et al, 2004;Molinari et al, 1993;Sofer et al, 1999;Tateda et al, 2001). Furthermore, CF patients showed significant improvement in pulmonary function with the use of macrolides without any effect on the total Pseudomonas population (Fujii et al, 1995;Saiman et al, 2003). Despite its success in decreasing P. aeruginosa virulence, macrolides are not ideal because, like any other antibiotic, excessive usage is associated with bacterial resistance.…”

Long-term macrolide treatment for chronic respiratory disease

“…These unexpected results were attributed to a previously unknown anti-inflammatory effect of erythromycin rather than to its antimicrobial properties. In fact, erythromycin 600 mg daily for a month has been shown to reduce the number of neutrophils and the concentration of IL-8 in BALF of DPB patients regardless of P. aeruginosa infection [15]. In addition, the maximal serum and sputum levels of erythromycin have been reported to be below the minimum inhibitory concentration of the relevant pathogens (Haemophilus influenzae and P. aeruginosa), thus confirming that it is unlikely that the beneficial effect of erythromycin in DPB purely results from its antibacterial activity [16].…”

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

“…Long-term treatment with low-dose macrolides, particularly erythromycin (EM), improves respiratory symptoms, lung function parameters, arterial oxygen tension, and imaging findings in DPB [7][8][9]. The administration of low-dose EM to DPB patients with PA infection leads to an improvement of the 10-yr survival rate from 12.4% tow90% [10]. It was shown recently that the administration of low-dose EM, over an 8-week period, significantly reduces sputum volume and improves lung function in severe idiopathic bronchiectasis [11].…”