ru-66647 and Chlamydia-Infections

The efficacy of telithromycin, a new ketolide antibiotic, was investigated in the treatment of acute Chlamydia pneumoniae infection in a mouse model.. C57BL/6J mice were inoculated intranasally, and the effects of three different doses of telithromycin (25, 50 and 100 mg/kg) were assessed after 5 and 10 days of treatment. Lungs for culture, PCR, histopathology, and blood for serum samples were collected immediately after each treatment period and at 3 weeks post-inoculation. C. pneumoniae-specific antibodies were analysed, and the effect of treatment was assessed by culture, detection of C. pneumoniae DNA and determination of histopathological inflammatory changes in mouse lungs.. Culture negativity in the lungs was achieved with the higher doses, 50 and 100 mg/kg, after 10 days of treatment. C. pneumoniae DNA was not totally eradicated with the treatments, but the groups treated with 50 and 100 mg/kg doses for 10 days had the lowest DNA positivity rates (10%) 3 weeks after the inoculation. In lung histopathology, the efficacy of telithromycin on inflammatory changes was also dose-dependent: higher doses were more effective in reducing the inflammatory reaction. Overall, the 25 mg/kg dose had a weaker effect compared with the others.. Telithromycin had both time- and dose-dependent effects on the eradication of chlamydia and on reducing infection-induced inflammatory changes in mouse lungs.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Chlamydia Infections; Chlamydophila pneumoniae; DNA, Bacterial; Dose-Response Relationship, Drug; Female; Immunoglobulin G; Inflammation; Ketolides; Lung; Macrolides; Mice; Mice, Inbred C57BL; Pneumonia, Bacterial; Reverse Transcriptase Polymerase Chain Reaction

Chronic Chlamydia pneumoniae infections have been associated with atherosclerosis, but clear knowledge about how these infections should be treated is lacking. We studied the effect of a new ketolide antibiotic, telithromycin, on chronic C. pneumoniae lung infection. Female C57BL/6J mice on a 0.2% cholesterol diet were inoculated intranasally with C. pneumoniae either two or three times every fourth week. Telithromycin was given to the mice subcutaneously at 75 mg/kg of body weight once daily for 5 or 10 days, starting at 3 days after the last inoculation. Samples were taken at 4 and 12 weeks after the last inoculation. The presence of C. pneumoniae DNA in lung tissue was demonstrated by PCR and the detection of lipid accumulation in the aortic sinus by Oil-Red-O staining. C. pneumoniae DNA positivity and inflammatory reactions in the lung tissue of the mice inoculated twice were significantly affected by treatment after both inoculations or only after the second inoculation at 12 weeks. Intimal lipid accumulation in the aortic sinus was also slightly but significantly less abundant in the mice treated after both inoculations compared to the levels in those treated only after the second inoculation for 10 days (geometric means, 823 and 4,324 microm(2), respectively; P = 0.033). No differences between the infected, untreated controls and the group inoculated three times and treated for 5 days were seen. We conclude that telithromycin is effective in preventing the development of chronic C. pneumoniae infection and intimal lipid accumulation in C56BL/6J mice when the treatment is given after each inoculation.

Topics: Animals; Aorta, Thoracic; Chlamydia Infections; Chlamydophila pneumoniae; Chronic Disease; DNA; Ketolides; Lipid Metabolism; Lung; Mice; Mice, Inbred C57BL; Myocardium; Reverse Transcriptase Polymerase Chain Reaction; Sinus of Valsalva

The in-vitro activity of HMR 3647, a novel ketolide, was investigated in comparison with those of erythromycin A, roxithromycin, clarithromycin (14-membered ring macrolides), amoxycillin-clavulanate and ciprofloxacin against 719 recent clinical Gram-positive, Gram-negative and anaerobic isolates and type cultures. HMR 3647 generally demonstrated greater activity than the other compounds with MIC90s of < or =0.5 mg/L, except for Staphylococcus epidermidis (MIC90 > 128 mg/L), Haemophilus influenzae (MIC90 = 2 mg/L), Enterococcus faecalis (MIC90 = 2 mg/L), Enterococcus faecium (MIC90 = 1 mg/L) and the anaerobes, Bacteroides fragilis (MIC90 = 2 mg/L) and Clostridium difficile (MIC90 = 1 mg/L). In general, an increase in the size of the inoculum from 10(4) to 10(6) cfu on selected strains had little effect on the MICs of HMR 3647. Additionally, the in-vitro activity of HMR 3647 was not affected by the presence of either 20 or 70% (v/v) human serum. The antichlamydial activity of HMR 3647 was generally greater than that of commonly used antichlamydial antimicrobials.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bacterial Infections; Chlamydia; Chlamydia Infections; Ciprofloxacin; Humans; Ketolides; Lactams; Macrolides; Microbial Sensitivity Tests; Serum Bactericidal Test