Telithromycin Inhibits the Number of Viable Bacteria but Not Lymphocyte Accumulation in a Murine Model of Chronic Respiratory Infection

Yanagihara, Katsunori; Kuroki, Misuzu; Higuchi, Norihide; Ohno, Hideaki; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Hirakata, Yoichi; Mukae, Hiroshi; Tomono, Kazunori; Mizuta, Yohei; Kadota, Jun‐ichi; Tsukamoto, Kazuhiro; Kohno, Shigeru

doi:10.1159/000098244

Cited by 3 publications

(3 citation statements)

References 24 publications

(23 reference statements)

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“…However, we recently reported that telithromycin significantly reduced the number of viable bacteria, but had no effect on the proliferation of lymphocytes in an experimental murine model of chronic respiratory infection in vivo. 24 In contrast, clarithromycin decreased the number of lymphocytes, but had no effect on the number of viable bacteria in the lung. This suggests that telithromycin and clarithromycin have different effects on chronic respiratory infections caused by P. aeruginosa.…”

Section: Discussionmentioning

confidence: 95%

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin

Ishimoto

Mukae

Sakamoto

et al. 2008

Journal of Antimicrobial Chemotherapy

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Objectives: Mucus hypersecretion is a prominent feature in patients with chronic respiratory tract infections such as cystic fibrosis and diffuse panbronchiolitis, and the clinical effectiveness of macrolide antibiotics has been reported in these patients. Because human neutrophil peptide-1 (HNP-1), an antimicrobial peptide in neutrophils, exists in high concentrations in the airway fluid of these patients, we examined the direct effect of HNP-1 on MUC5AC mucin production using NCI-H292 cells. The effects of macrolide antibiotics on the response were also examined.Methods: MUC5AC synthesis was assayed using RT-PCR and ELISA. Phosphorylation of ERK1/2 was determined by western blotting.Results: Stimulation with HNP-1 or lipopolysaccharide (LPS) derived from Pseudomonas aeruginosa increases the production of MUC5AC mRNA and protein, and an additive effect was found upon co-stimulation with both HNP-1 and LPS. Azithromycin and clarithromycin had inhibitory effects on overproduction of MUC5AC induced by HNP-1 or LPS stimulation. Telithromycin also had an inhibitory effect on MUC5AC production induced by LPS, but not on production by HNP-1. Phosphorylation of ERK1/2 was induced by HNP-1 or LPS stimulation, and azithromycin, clarithromycin and telithromycin had inhibitory effects on ERK1/2 phosphorylation induced by LPS, but not by HNP-1.Conclusions: These findings suggest that neutrophil-derived defensins as bacterial components contribute to excessive mucus production in patients with respiratory tract infections, and that macrolide and ketolide antibiotics directly inhibit these actions by interfering with intracellular signal transduction. However, the mechanism of telithromycin inhibition of MUC5AC synthesis may differ from the response induced by azithromycin and clarithromycin.

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Section: Discussionmentioning

confidence: 95%

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin

Ishimoto

Mukae

Sakamoto

et al. 2008

Journal of Antimicrobial Chemotherapy

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“…Helicobacter pylori at sub-MIC concentrations 10,11 . Telithromycin has also been reported to reduce the number of viable bacteria during P. aeruginosa infection by via inhibiting biofilm formation 12 .…”

Section: Previous Reports Indicated That Telithromycin Has Effects Agmentioning

confidence: 99%

Subinhibitory concentrations of telithromycin, clarithromycin and azithromycin reduce methicillin-resistant Staphylococcus aureus coagulase in vitro and in vivo

Yanagihara

Morinaga

Nakamura

et al. 2008

Journal of Antimicrobial Chemotherapy

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“…In recent years, chemical agents, besides antibiotics, possessing potent antimicrobial properties have attracted considerable attention [9]. Ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl] benzylamine), a mucolytic agent, seems to have additional antioxidant and anti-inflammatory properties in the treatment of pulmonary infectious diseases characterized by impaired mucociliary clearance [10].…”

Section: Introductionmentioning

confidence: 99%

Effect of Ambroxol on Pneumonia Caused by <i>Pseudomonas aeruginosa</i> with Biofilm Formation in an Endotracheal Intubation Rat Model

Fang¹,

Wang

Hu³

et al. 2011

Chemotherapy

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Background:Pseudomonas aeruginosa, especially the mucoid phenotype, is responsible for most of the morbidity and mortality in ventilator-associated pneumonia. Although ambroxol is widely used in neonatal lung problems as a mucolytic as well as an antioxidant agent, its anti-infective role is not well demonstrated by studies in vivo. Objective: To explore the effect of ambroxol on the biofilms of mucoid P. aeruginosa and on the associated lung infection using a rat model. Methods: We developed a rat model of acute lung infection by endotracheal intubation with a tube covered with mucoid P. aeruginosa biofilm. Then, we studied the effect of ambroxol on the biofilm using saline treatment as a control. Subsequently, we studied the microstructure of the biofilm, bacterial count in the tubes and lungs, pathological changes that occurred in the lungs, and the cytokine response. Results: Alteration of the microstructure of the biofilm with ambroxol treatment was demonstrated by scanning electron microscopy. The bacterial counts on the biofilm-covered tube in the ambroxol-treated group were significantly lower than those in the saline-treated group on both post-bacterial challenge days 4 and 7 (p < 0.05). The bacterial counts in lungs of the ambroxol-treated group and of the saline-treated group on post-bacterial challenge day 7 were not significantly different (p > 0.05). The pathological changes in lungs were milder with the effect of ambroxol. The cytokine responses, namely the level of IFN-γ and the ratio of IFN-γ and IL-10, were also reduced with the effect of ambroxol. Conclusion: We demonstrated that the ambroxol treatment could destroy the structure of the biofilm on the tube used for intubation and decrease the bacterial load. Further, the reduced cytokine response and milder pathological changes in lungs in an endotracheal intubation rat model indicate that ambroxol can attenuate the damage caused by biofilm-associated infection in the lung.

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Telithromycin Inhibits the Number of Viable Bacteria but Not Lymphocyte Accumulation in a Murine Model of Chronic Respiratory Infection

Cited by 3 publications

References 24 publications

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin

Different effects of telithromycin on MUC5AC production induced by human neutrophil peptide-1 or lipopolysaccharide in NCI-H292 cells compared with azithromycin and clarithromycin

Subinhibitory concentrations of telithromycin, clarithromycin and azithromycin reduce methicillin-resistant Staphylococcus aureus coagulase in vitro and in vivo

Effect of Ambroxol on Pneumonia Caused by <i>Pseudomonas aeruginosa</i> with Biofilm Formation in an Endotracheal Intubation Rat Model

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