Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus.
OBJECTIVE
To assess the efficacy of telavancin, a rapidly bactericidal lipoglycopeptide, and three comparator agents in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus (MSSA).


METHODS
Female Bagg inbred albino c-strain (BALB/c) mice were rendered neutropenic and infected by intranasal inoculation (50 microL) of 10(7) cfu of S. aureus ATCC 29213. Infected mice were then allocated to one of five treatment arms: subcutaneous (sc) telavancin 40 mg/kg every 12 h, sc nafcillin 40 mg/kg every 4 h, sc vancomycin 110 mg/kg every 12 h, intravenous linezolid 80 mg/kg every 12 h or no drug (control group). Test compounds were studied under low and high pre-treatment titre conditions by initiating drug treatment at 4 and 8 h post-inoculation, respectively. Drug doses were calculated to simulate human exposures (area under the curve or t > MIC) at therapeutic doses. Lungs were harvested and homogenized 24 and 48 h after inoculation to determine the bacterial titre.


RESULTS
At 48 h post-inoculation in the low and high pre-treatment titre groups, respectively, telavancin produced greater reductions (from pre-treatment values) in bacterial burden (-4.3 and -3.2 log(10) cfu/g) than nafcillin (-1.3 and -1.8 log(10) cfu/g), vancomycin (-2.9 and -2.2 log(10) cfu/g) and linezolid (-0.4 and +0.3 log(10) cfu/g).


CONCLUSIONS
These findings support the potential clinical utility of telavancin in the treatment of MSSA pneumonia.
Hegde
Sharath S
SS
Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. shegde@theravance.com
Reyes
Noe
N
Skinner
Robert
R
Difuntorum
Stacey
S
D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D000077427:Lipoglycopeptides; D016106:Methicillin Resistance / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C487637:telavancin