Our aim was to evaluate the effects of eradication and the incidence of secondary resistance by long-term low-dose daily 14-membered-ring macrolide therapy on Helicobacter pylori ( H. pylori) infection in patients with chronic lower respiratory tract inflammatory disease. In a retrospective analysis, we studied the seroprevalence of H. pylori IgG in 90 patients with inflammation of the lower respiratory tract (68 had been treated with macrolide and 22 served as controls). Then, in a prospective analysis, we evaluated the eradication effect of macrolide therapy by the decline of IgG values and the (13)C-urea breath test. Only long-term macrolide use significantly affected the seroprevalence of H. pylori IgG. However, macrolide therapy did not reduce the H. pylori IgG values in 24 patients and did not eradicate H. pylori in (13)C-urea breath tests. Chemosensitivity testing was performed on three H. pylori strains obtained by gastric biopsy from patients in whom the disease could not be eradicated. Only one strain demonstrated a resistant character. Daily long-term low-dose 14-membered-ring macrolide therapy for patients with lower respiratory inflammatory disease may not be sufficient to eradicate H. pylori, but some strains do not acquire a resistant nature.
[Show abstract][Hide abstract] ABSTRACT: Twelve clarithromycin-resistant Helicobacter pylori isolates (100% of resistant isolates examined) from seven different patients each contained an A-->G transition mutation within a conserved loop of 23S rRNA. A-->G transition mutations at positions cognate with Escherichia coli 23S rRNA positions 2058 and 2059 were identified. Clarithromycin-susceptible H. pylori isolates from 14 different patients displayed no polymorphisms in a conserved loop within domain V of 23S rRNA. The study is the first to report mutations in H. pylori associated with resistance to an antimicrobial agent used in established peptic ulcer treatment regimens.
Antimicrobial Agents and Chemotherapy 02/1996; 40(2):477-80. · 4.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macrolides have been used for decades as an important chemotherapeutic agent in the treatment of infectious diseases. In the last 10 years there has also been increasing interest in the interaction between macrolide antibiotics and the immune system. The aim of this review is to focus on the anti-inflammatory action of erythromycin and its derivatives in the treatment of chronic sinusitis and nasal polyps. Systematic clinical investigations have been few and to the author's knowledge there have been no placebo-controlled studies. However there have been, especially from Japan, a number of clinical reports stating that long-term, low-dose macrolide antibiotics are effective in treating chronic sinusitis incurable by surgery or glucocorticosteroid treatment, with an improvement in symptoms varying between 60% and 80% in different studies. In animal studies macrolides have increased mucociliary transport, reduced goblet cell secretion and accelerated apoptosis of neutrophils, all factors that may reduce the symptoms of chronic inflammation. There is also increasing evidence in vitro of the anti-inflammatory effects of macrolides. Several studies have shown macrolides to inhibit interleukin gene expression for IL-6 and IL-8 and also to inhibit the expression of intercellular adhesion molecule essential for the recruitment of inflammatory cells. There is also evidence in vitro, as well as clinical experience, showing that macrolides reduce the virulence and tissue damage caused by chronic bacterial colonization without eradicating the bacteria. The benefit of long-term, low-dose macrolide treatment seems to be that it is, in selected cases, effective when steroids fail. The exact mechanism of action is not known, but it probably involves downregulation of the local host immune response as well as a downgrading of the virulence of the colonizing bacteria. In the future, placebo-controlled studies should be performed to establish the efficacy of macrolides if this treatment is to be accepted as evidence-based medicine.
[Show abstract][Hide abstract] ABSTRACT: Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease of the airways with a high rate of mortality despite treatment with a combination of antibiotics and the use of supportive therapy such as oxygen administration. Low-dose erythromycin therapy (EM) (400 to 600 mg/d) has been found to improve the survival of patients with DPB, and most patients with DPB in Japan have been treated with this erythromycin regime since 1984. The purpose of this study was to evaluate the effects of treatment with erythromycin on the survival rate of patients with DPB in Japan. We compared the survival rates of 498 patients with DPB after dividing them into three groups according to the date of their first medical examination (Group a: 1970-1979, Group b: 1980-1984, Group c: 1985-1990). DPB had been diagnosed in these patients using the criteria of the Ministry of the Health and Welfare Diffuse Lung Disease Committee (MHW-DLDC), which includes chronic productive cough, shortness of breath, presence of roentgenologically smoldering symmetrical granular shadows in the middle and lower lung fields, limitation of airflow without decrease in DLCO, elevated serum cold hemagglutinin titers, and/or narrowing bronchiolus with infiltration of lymphocytes and foamy alveolar macrophages. These patients were registered in the DPB research group of the Ministry of Health and Welfare (MHW). Survival rates were statistically compared using the generalized-Wilcoxon test. The survival rate of Group c was significantly higher than that of Groups a (p < 0.0001) and b (p < 0. 0001). In Group c, eight of 87 patients died; five died in the EM nontreated subgroup (n = 24), and three died in the EM-treated subgroup (n = 63). There was a significant difference in the survival rates between the two subgroups in Group c (p < 0.001). Treatment with EM was associated with a significant improvement in the rate of survival of patients with DPB. The efficacy of EM treatment increased the survival rate of patients with DPB, which was more significant in the older than in the younger patients.
American Journal of Respiratory and Critical Care Medicine 07/1998; 157(6 Pt 1):1829-32. DOI:10.1164/ajrccm.157.6.9710075 · 13.00 Impact Factor
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