ru-66647 and Abdominal-Abscess

The efficacy of telithromycin (HMR 3647), a new ketolide, in the treatment of experimental Bacteroides fragilis intraabdominal abscess in young and senescent mice was evaluated. Two different age groups of mice, young (2-3 months) and senescent (18-24 months) were used in this study. Telithromycin (50mg/kg/bid) was compared with clindamycin and metronidazole, both administered in 100 mg/kg/bid doses. Telithromycin cured the infection in 74% of the young and 67% of the old mice but this difference was not significant. Telithromycin efficacy was comparable to that of clindamycin which cured 82% of the young and 75% of the old, but was superior to the efficacy of metronidazole, which cured 61% of the young and 50% of the senescent mice. Young animals that were not cured by any of the three antibiotics showed decrease in the viable bacterial cell counts by two logs while the senescent mice had a one log difference. Serum, pus and tissue concentrations of telithromycin were five-fold higher in the old mice than in the young. Age by itself had no adverse effect on therapeutic outcome of any of the three antibiotics used.

Topics: Abdominal Abscess; Age Factors; Aging; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Biological Availability; Body Composition; Body Water; Clindamycin; Drug Evaluation, Preclinical; Injections, Subcutaneous; Ketolides; Male; Metronidazole; Mice; Tissue Distribution

Telithromycin is one of the ketolides, characterised by a 3-keto group instead of L-cladinose and a C(11)-C(12) carbamate link by an alkyl chain to a pyridinum and imidazolium ring side chain. We evaluated in vitro and in vivo antibacterial activities of telithromycin against gynaecological pathogens.. In the vitro study, the antibacterial activity of telithromycin against 180 isolates (isolated in the year 2000) of Streptococcus agalactiae (n = 33), Enterococcus faecalis (n = 22), Neisseria gonorrhoeae (n = 30), Peptostreptococcus anaerobius (n = 20), Finegoldia magna (n = 20), Bacteroides fragilis (n = 25) and Prevotella bivia (n = 30) was compared with that of erythromycin A, clarithromycin, azithromycin, ampicillin and levofloxacin. In the in vivo study, the efficacy of telithromycin was evaluated using experimental intra-abdominal abscesses in mice caused by B. fragilis (minimum inhibitory concentration of telithromycin 0.5 mg/l).. In the in vitro study, telithromycin inhibited more than 50% of clinical isolates of S. agalactiae, E. faecalis, N. gonorrhoeae, P. anaerobius, F. magna, B. fragilis and P. bivia at concentrations of 0.016, 0.063, 0.063, 0.032, 0.032, 0.5 and 0.25 mg/l, respectively. Telithromycin inhibited more than 90% of these clinical isolates at concentrations of 0.016, 4, 0.125, 0.063, 0.063, 4 and 1 mg/l, respectively. In the in vivo study, telithromycin inhibited abscess formation and significantly decreased viable cell counts in abscesses in comparison with the untreated group.. These in vitro and in vivo antibacterial activities suggest that telithromycin could be a potential candidate for the treatment of bacterial infections complicated by chlamydial infection.

Topics: Abdominal Abscess; Animals; Anti-Bacterial Agents; Bacterial Infections; Bacteroidaceae; Bacteroides fragilis; Enterococcus faecalis; Female; Genital Diseases, Female; Gram-Negative Aerobic Rods and Cocci; Gram-Positive Cocci; Ketolides; Macrolides; Mice; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Peptostreptococcus; Prevotella; Streptococcus agalactiae