Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages. (1/22)

There is evidence that macrolide antibiotics are effective in the treatment of chronic airway inflammatory diseases, probably through actions other than their antibacterial properties. In order to determine whether macrolides affect the nitric oxide-generating system in the respiratory tract, rat pulmonary alveolar macrophages (PAMs) were studied in vitro. The release of NO was assessed by direct measurement with a specific amperometric sensor for this molecule, and the expression of type II NO synthase (NOS) messenger ribonucleic acid (mRNA) was determined by Northern blotting. Incubation of PAMs with lipopolysaccharide from Escherichia coli and recombinant human interferon-gamma caused release of NO, which was accompanied by induction of type II NOS mRNA. The release of NO was reduced by coincubation of cells with the macrolides erythromycin, clarithromycin and josamycin in a concentration-dependent manner, the maximal inhibition being 73+/-10, 81+/-6 and 84+/-9%, respectively, but was not altered by amoxycillin or cefaclor. These macrolides likewise inhibited the induction of type II NOS mRNA, whereas no inhibitory effects were observed with amoxycillin or cefaclor. These results suggest that macrolide antibiotics specifically inhibit type II NO synthase gene expression and consequently reduce NO production by rat pulmonary alveolar macrophages, which might result in attenuation of airway inflammation.  (+info)

A new quadruple therapy for Helicobacter pylori using tripotassium dicitrato bismuthate, furazolidone, josamycin and famotidine. (2/22)

BACKGROUND: In our previous study, a triple therapy using tripotassium dicitrato bismuthate (TDB), josamycin and furazolidone achieved a suboptimal cure rate of Helicobacter pylori infection. AIM: To investigate whether the addition of an antisecretory agent raises the cure rate using this regimen. METHODS: One hundred and twenty H. pylori positive patients with peptic ulcer disease or functional dyspepsia were randomly assigned to receive 1-week quadruple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d., josamycin 1000 mg b.d. and famotidine 20 mg b.d. (BFJF group), or triple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d. and clarithromycin 250 mg b.d. (BFC group). H. pylori status was assessed by histology and culture of gastric biopsy specimens before and at least 4 weeks after completion of therapy. RESULTS: Seven patients (three in the BFJF group and four in the BFC group) dropped out. Eradication rates (intention-to-treat/per protocol) were 90%/95% in the BFJF group and 82%/88% in the BFC group, respectively (P > 0.05). Duodenal ulcer healing rates were 94% (16/17) in the BFJF group and 80% (20/25) in the BFC group, respectively (P > 0.05). Mild side-effects occurred in 11 (18%) patients in the BFJF group and 10 (17%) in the BFC group (P > 0.05). CONCLUSIONS: One-week quadruple therapy consisting of TDB, furazolidone, josamycin and famotidine achieves a high cure rate of H. pylori infection.  (+info)

Effect of clarithromycin on chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation in an experimental murine model. (3/22)

Fourteen-membered macrolides (e.g. clarithromycin and erythromycin), but not 16-membered macrolides (e.g. josamycin), are effective in diffuse panbronchiolitis. However, there are no studies that have compared the effects of 14- and 16-membered macrolide antibiotics on biofilm formation. Treatment with high-dose clarithromycin (100 mg/kg) resulted in a significant decrease in the number of viable bacteria in an experimental murine model. Josamycin at a dose of up to 100 mg/kg had no effect on the number of viable bacteria in the lung. Our results may explain, at least in part, the clinical efficacy of 14-membered macrolide antibiotics in patients with chronic pneumonia caused by Pseudomonas aeruginosa.  (+info)

In vitro and ex vivo effects of erythromycin A, azithromycin and josamycin on the splenic response to specific antigens and mitogens. (4/22)

The immunomodulatory properties of antimicrobial agents and their clinical impact have been the focus of worldwide interest in recent years. In this study, the effects of different treatments with 14-, 15- and 16-membered ring macrolides on the mitogen-induced proliferative response of lymphocytes and the splenic response to immunization with sheep erythrocytes have been tested by in vitro and ex vivo assays in a murine experimental model. We observed that the in vivo administration of these antibiotics to mice induces a compensatory mechanism that abrogates the suppression observed by in vitro assays. Thus, physiological parameters may be important when testing the immunopharmacological effects of antibiotics.  (+info)

Mutations in 23S rRNA account for intrinsic resistance to macrolides in Mycoplasma hominis and Mycoplasma fermentans and for acquired resistance to macrolides in M. hominis. (5/22)

The mechanisms of intrinsic resistance of Mycoplasma hominis to 14- and 15-membered macrolides were investigated in comparison with those of M. pneumoniae, which is naturally susceptible to macrolides. Radiolabeled erythromycin was not accumulated by M. hominis PG21, but addition of an ABC transporter inhibitor increased the level of erythromycin uptake more than two times, suggesting the existence of an active efflux process. The affinity of [(14)C]erythromycin to ribosomes isolated from M. hominis was dramatically reduced relative to that to ribosomes isolated from M. pneumoniae. The nucleotide sequences of 23S rRNA of both ribosomal operons rrnA and rrnB and ribosomal proteins L4 and L22 of M. hominis were obtained. Compared to the sequence of M. pneumoniae, M. hominis harbored a G2057A transition in its 23S rRNA sequence, as did M. fermentans, another mycoplasma that is erythromycin resistant. An additional C2610U change was also found in the sequence of M. hominis. Moreover, two M. hominis clinical isolates with acquired resistance to 16-membered macrolides were examined for mutations in domain II and domain V of 23S rRNA and in ribosomal proteins L4 and L22. Compared to the sequence of reference strain PG21, one isolate harbored a A2059G transition and a C2611U transition in one of the two rrn operons, while the other one was mutated only at position 2059, also on the same operon. No mutation was found in the two ribosomal protein sequences. Overall, the present study is an exhaustive characterization of the intrinsic resistance of M. hominis to 14- and 15-membered macrolides and the first description of mycoplasma clinical isolates resistant to macrolide, lincosamide, and streptogramin antibiotics harboring a mutation at position 2611 in the 23S rRNA.  (+info)

Activity of telithromycin against penicillin-resistant Streptococcus pneumoniae isolates recovered from French children with invasive and noninvasive infections. (6/22)

We compared the activities of telithromycin, erythromycin, azithromycin, josamycin, penicillin G, amoxicillin, cefpodoxime, and ceftriaxone against invasive and noninvasive non-penicillin-susceptible Streptococcus pneumoniae isolates recovered from children. Of the 186 isolates tested, 89% were positive for erm(B) by PCR. Telithromycin had the lowest MICs, with MICs at which 90% of the isolates tested are inhibited of 0.032 and 0.25 micro g/ml for erythromycin-sensitive and -resistant isolates, respectively.  (+info)

Modification of phagocytosis and cytokine production in peritoneal and splenic murine cells by erythromycin A, azithromycin and josamycin. (7/22)

OBJECTIVES: The aim of this study was to determine whether pre-incubation of peritoneal or splenic cells with different doses of the macrolides erythromycin A (14-membered ring), azithromycin (15-membered ring) and josamycin (16-membered ring) affects their phagocytic activity or cytokine production. METHODS: Peritoneal and splenic cells from BALB/c mice were pre-incubated with different concentrations of these antibiotics, those similar to serum levels attained with the treatment schedules used in human therapy. RESULTS: From our observations of phagocytic activity and IL-12 production by peritoneal cells, these macrolide antibiotics seem to act mainly as immunosuppressive agents, although they induce peritoneal cells to increase IL-18 production and splenic cells IL-4 production. CONCLUSIONS: Macrolide antibiotics can interfere with the Th1 cell-amplifying activity of IL-18 in conjunction with IL-12 and, in contrast, may induce a Th2 cell response in an IL-4-dependent manner. These results could improve their therapeutic use especially in immunosuppressed patients.  (+info)

Suppression of matrix metalloproteinase production from nasal fibroblasts by macrolide antibiotics in vitro. (8/22)

It is well known that low-dose and long-term administration of macrolide antibiotics favourably modify the clinical status of chronic airway inflammatory diseases. However, the therapeutic mode of action of macrolide antibiotics is not well understood. The present study aimed to examine the influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts (NPF) in vitro. NPF, at a concentration of 2.5 x 10(5) cells x mL(-1), were stimulated with tumour necrosis factor (TNF)-alpha in the presence of various concentrations of RXM or JM for 24 h. MMP-2 and -9 levels in culture supernatants were analysed by ELISA, and MMP mRNA expression was examined by RT-PCR. The influence of RXM on nuclear factor (NF)-kappaB and activator protein (AP)-1 activation was also examined. Addition of RXM (but not JM) at 5.0 and 7.5 microg x mL(-1) significantly suppressed the production of MMP-2 and -9 from NPF induced by TNF-alpha stimulation. RXM also suppressed MMP mRNA expression through the inhibition of NF-kappaB and AP-1 activation. The present results suggest that the suppressive activity of roxithromycin on MMP-2 and -9 production is, in part, responsible for the therapeutic action of macrolides on chronic airway inflammatory diseases.  (+info)