Efficacy of telavancin in a murine model of bacteraemia induced by methicillin-resistant Staphylococcus aureus.
OBJECTIVE
The efficacy of telavancin, a bactericidal lipoglycopeptide, was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in an immunocompromised murine model of bacteraemia.


METHODS
Immunocompromised mice were inoculated intraperitoneally with S. aureus ATCC 33591 and treated with two subcutaneous doses (once every 12 h) of vehicle or test compound. Mouse pharmacokinetic data were generated and used to choose doses of telavancin (40 mg/kg) and vancomycin (110 mg/kg) in order to equate clinical exposures. Reduction in bacterial titre (in blood and spleen) and mortality were the two pharmacodynamic endpoints of the study.


RESULTS
Mortality was 100% in animals treated with vehicle or vancomycin but was significantly lower (7%) in telavancin-treated animals. Telavancin produced significantly greater reductions in blood and spleen bacterial titres compared with vancomycin.


CONCLUSIONS
The data described here demonstrate that telavancin's in vivo bactericidal activity is superior to that of vancomycin against a single strain of MRSA and results in successful infection resolution and, consequently, improved survival in the murine bacteraemia model.
Reyes
Noe
N
Theravance, Inc., 901 Gateway Boulevard, South San Francisco CA 94080, USA.
Skinner
Robert
R
Benton
Bret M
BM
Krause
Kevin M
KM
Shelton
Josephine
J
Obedencio
Glenmar P
GP
Hegde
Sharath S
SS
D000617:Aminoglycosides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy*; D001769:Blood / Q000382:microbiology; D004195:Disease Models, Animal; D000077427:Lipoglycopeptides; D016106:Methicillin Resistance; D051379:Mice; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D016019:Survival Analysis; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin