The antibacterial activity of azithromycin (MIC₉₀: 2μg/mL) against Haemophilus influenzae was 4 times stronger than that of clarithromycin and ampicillin, but was weaker than cefdinir and cefcapene. On the administration of a drug twice daily for 3 days at a dose of 50mg/kg in murine bronchopneumonia, efficacy in mice treated with azithromycin and cefcapene pivoxil was significantly superior to that in mice treated with clarithromycin, ampicillin, and cefdinir. In contract, on the administration of 1 dose of 100mg/kg, the efficacy of azithromycin and cefcapene pivoxil was significantly superior to that in mice treated other drugs until 24h after administration. However, at 48h after administration, the efficacy of azithromycin was significantly superior to all other drugs containing cefcapene pivoxil. The antibacterial activity of cefcapene, cefdinir, and ampicillin was 4 times or more stronger than azithromycin. Since the concentration of azithromycin in lung tissue was 100 times or more than that in serum, this high distribution in tissue reflected the good efficacy of azithromycin.

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Electrolyzed acidic and alkaline water generated from tap water containing a small amount of salt by electrolysis is strongly bactericidal (acidic) and degrades organic materials (alkaline). Food may become contaminated by pathogenic microorganisms from kitchen equipment and the hands during food preparation. To prevent food poisoning, we studied disinfection using electrolyzed water on several kitchen materials. Applying sodium hypochlorite (residual chlorine=100mg/L) and acidic electrolyzed water (pH 2.7, residual chlorine=35-40mg/L) against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium adhering to tile, stainless steel, and gauze containing 0.1% protein killed almost all bacteria. When 1% protein was added to the bacteria, they survived on the above materials after disinfection with sodium hypochlorite and acidic electrolyzed water. Almost all bacteria were killed by disinfection with acidic electrolyzed water after washing with alkaline electrolyzed water. Disinfecting contaminated materials such as cutting boards, boots, and knives with acidic electrolyzed water after washing with alkaline electrolyzed water markedly decreased bacteria to the same level as with commonly used procedures such as disinfection with sodium hypochlorite after washing with tap water. These findings suggest that washing and disinfection with electrolyzed water effectively prevents bacterial contamination of foods because electrolyzed water can be used in the same way as tap water.

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Although fosfomycin (FOM) is known to be a unique antibiotic that has an immunosuppuressive function, the effects of FOM on autoimmune diseases remain unclear. In this study, we report a novel role of FOM in the tissue destruction of an organ-specific autoimmune disease in a murine model of Sjögren's syndrome (SS). When we administered FOM to a murine model of autoimmune exocrinopathy in SS from 4 weeks to 8 or 12 weeks of age, fewer autoimmune lesions were found in the salivary and lacrimal glands of the mice at 12 weeks than in the control mice. In addition, a decreased proportion of TUNEL⁺ apoptotic epithelial duct cells was observed in the mice given FOM from 4 weeks to 8 weeks. We also found that preincubation with low concentrations of FOM (0.001μg/mL-1.0μg/mL) inhibits anti-Fas-induced apoptosis in human salivary gland cell lines (HSG and HSY). We detected an inhibitory effect of FOM on proteolysis of α-fodrin in HSG and HSY cells with Fas-mediated apoptosis. Furthermore, treatment with FOM suppressed caspase activities (ICE and CPP-32) in salivary gland cells stimulated with anti-Fas mAb. These results suggest that FOM has a theraputic effect on Sjögren's syndrome by inhibiting apoptosis in salivary gland cells.

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Clarithromycin (CAM), a fourteen-membered macrolide, has some effects as a biological response modifier in addition to its antibiotic effects. Long-term CAM treatment improves the prognosis and quality of life of patients with inoperable non-small cell lung cancer. In the present study, we evaluated the expression of cytokine mRNA in peripheral blood mononuclear cells taken from these patients treated with CAM and in spleen cells from an experimental mouse model. The mice were inoculated subcutaneously with Lewis lung cancer cells and treated with or without CAM. Two weeks after the inoculation, the mice were sacrificed and the spleen cells were examined. The expression of both IL-12 and IFN-γmRNA were increased in humans after CAM treatment (1-3months). On the contrary, the expression of IL-10mRNA decreased. As in the human study, the expression of both IL-12 and IFN-γmRNA increased in mice, while the expression of both IL-6 and IL-10mRNA decreased. These results suggest that CAM treatment regulates the Th1/Th2 balance (stimulation of Th 1 type response and suppression of Th 2 type response) in both cancer-bearing patients and an experimental animal model.

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Bridging studies are being increasingly conducted in the clinical development of novel antibacterial drugs, and the fact that cases of chronic airway infection in Japan and acute exacerbation of chronic bronchitis in Western countries are assessed differently is a particular issue. Although this matter has been discussed frequently with Western investigators, this study was conducted it was thought to be important to make definite comparisons to consider future clinical evaluation methods for antibacterial drugs to be developed in Japan. We visited the O'Doherty Clinic in Wexford, Ireland. The clinic had participated in a Trovafloxacin phase III study and had experience with many cases of acute exacerbation of chronic bronchitis. We reviwed the diagnosis, severity, and inclusion criteria in individual cases through discussion with local physicians in charge and radiologists, and compared them with standards in Japan. In a detailed study of 18 cases, acute exacerbation of chronic bronchitis was found to be regarded as the clinical diagnosis, and the clinical course, the presence of purulent sputum, and the results of microscopic examination of gram-stained specimens were found to be most important. The CRP value, the peripheral white blood cell count, and the presence or absence of fever, which are the criteria required of Japanese standards, were not evaluated. As a result, the number of mild cases is slightly greater in Western countries than in Japan. Chest X-ray studies, on the other hand, showed that 5 cases had structural disorders, such as old pulmonary tuberculosis, pulmonary emphysema, or bronchiectasis, and thus it was obvious that chronic bronchitis was not the only subject of the assessments. However, cystic fibrosis lung was not included, and cases persistently secreting Pseudomonas aeruginosa were also excluded. Because of the emphasis given to sputum gram staining, the rate of identification of causative organisms was high. Although the number of comparatively studied cases was limited this time, Western cases of acute exacerbation of chronic bronchitis essentially resembled Japanese cases of chronic airway infection, and the largest defference was considered to be the tendency for Japanese cases to be slightly more severe.

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To assess the influence of perioprative administration of cefozopran on intestinal flora, we analyzed changes in bacterial counts in faeces obtained from 9 patients receiving 3 gram of cefozopran daily for 3 days after gastrectomy. Stool samples were collected before surgery and after 3-day cefozopran administration. No change was seen in total counts of aerobes or Escherichia coli. No significant decrease was seen in total counts of anaerobes. Bifidobacterium, Eubacterium, and Bacteriodes counts did not decreased after administration. No overgrowth was seen in Pseudomonas aeruginosa, Candida spp., Clostridium difficile, or methicillin-resistant Staphylococcus aureus, exept for Enterococcus app. Our results suggest that cefozopran did not disturb the ecological balance in intestinal flora after short-term administration.

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