title: Efficacy of Telavancin in a rabbit model of aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus or vancomycin-intermediate Staphylococcus aureus.
abstract: The activities of telavancin and vancomycin were compared in vitro and in the rabbit model of aortic valve endocarditis against a methicillin-resistant Staphylococcus aureus strain, COL, and a vancomycin-intermediate S. aureus (VISA) strain, HIP 5836. Telavancin was bactericidal in time-kill studies at a concentration of 5 microg/ml against both COL and HIP5836. Vancomycin was bacteriostatic at 5 microg/ml and bactericidal at 10 microg/ml against COL and was bacteriostatic at 10 microg/ml against VISA strain HIP 5836. Compared to untreated controls, a twice-daily regimen of 30 mg/kg of telavancin reduced mean aortic valve vegetation titers of the COL strain by 4.7 log(10) CFU/g after 4 days of therapy and sterilized 6/11 vegetations compared to 3.4 log(10) CFU/g with 3/10 vegetations sterilized for a regimen of twice-daily vancomycin, 30 mg/kg; these differences were not statistically significant. Telavancin was significantly more effective than vancomycin in the VISA model, producing a 5.5 log(10) CFU/g reduction versus no reduction in CFU with vancomycin. In experiments comparing 2-day regimens of telavancin at 30 mg/kg and 50 mg/kg twice daily, organisms were rapidly eliminated from vegetations, but the effect was not different between the two doses. These results suggest that telavancin may be an effective treatment for endocarditis and other serious staphylococcal infections accompanied by bacteremia, including infections caused by staphylococci not susceptible to vancomycin.
authors.affiliation: University of California at San Francisco, Division of Infectious Diseases at SFGH, Box 0811, San Francisco, CA 94143, USA.
authors.forename: Andres G
authors.initials: AG
authors.lastname: Madrigal
authors.forename: Li
authors.initials: L
authors.lastname: Basuino
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001021:Aortic Valve / Q000382:microbiology*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006349:Heart Valve Diseases / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D000077427:Lipoglycopeptides; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin