JAC Advance Access published online on November 9, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm417
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus
Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA
Received 27 July 2007; returned 9 September 2007; revised 2 October 2007; accepted 8 October 2007
* Corresponding author. Tel: +1-650-808-6432; Fax: +1-650-808-6441; E-mail: shegde{at}theravance.com
Objectives: 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 µL) of 107 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 log10 cfu/g) than nafcillin (–1.3 and –1.8 log10 cfu/g), vancomycin (–2.9 and –2.2 log10 cfu/g) and linezolid (–0.4 and +0.3 log10 cfu/g).
Conclusions: These findings support the potential clinical utility of telavancin in the treatment of MSSA pneumonia.
Key Words: mouse , MRSA , lipoglycopeptide , vancomycin , nafcillin
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. S. Lunde, S. R. Hartouni, J. W. Janc, M. Mammen, P. P. Humphrey, and B. M. Benton Telavancin Disrupts the Functional Integrity of the Bacterial Membrane through Targeted Interaction with the Cell Wall Precursor Lipid II Antimicrob. Agents Chemother., August 1, 2009; 53(8): 3375 - 3383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. LaPlante and L. A. Mermel In Vitro Activities of Telavancin and Vancomycin against Biofilm-Producing Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis Strains Antimicrob. Agents Chemother., July 1, 2009; 53(7): 3166 - 3169. [Abstract] [Full Text] [PDF]
|
|