In vivo efficacy of the new ketolide telithromycin (HMR 3647) in murine infection models.
We compared the oral antibacterial activities of telithromycin (HMR 3647), a new ketolide drug, in different infections induced in mice by Staphylococcus aureus, Streptococcus pneumoniae, streptococci, enterococci, and Haemophilus influenzae with those of various macrolides and pristinamycin. Unlike all other comparators, telithromycin displayed a high therapeutic activity, particularly in septicemia induced by erythromycin A-resistant pathogens, where the ketolide was the only active compound, displaying effective doses between 3 and 26 mg/kg of body weight. Against H. influenzae, telithromycin was the most effective compound. Telithromycin displayed bacteriostatic behavior against S. pneumoniae and H. influenzae. The ketolide was also active against thigh muscle infection induced by S. aureus. The pharmacokinetic properties of telithromycin accounted for its outstanding well-balanced oral in vivo efficacy against both gram-positive cocci, whatever their phenotype of resistance, and H. influenzae.
Bonnefoy
A
A
Infectious Diseases Group, Microbiology, Aventis Pharma-Hoechst Marion Roussel, 93235 Romainville Cedex, France. Alain.Bonnefoy@aventis.com
Guitton
M
M
Delachaume
C
C
Le Priol
P
P
Girard
A M
AM
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000517:prevention & control*; D001682:Biological Availability; D004917:Erythromycin / Q000627:therapeutic use; D006207:Half-Life; D007275:Injections, Intravenous; D048628:Ketolides; D018942:Macrolides; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D014769:Virginiamycin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D014769:Virginiamycin; D004917:Erythromycin; C106791:telithromycin