Format

Send to

Choose Destination
J Antimicrob Chemother. 2010 Apr;65(4):725-8. doi: 10.1093/jac/dkq028. Epub 2010 Feb 5.

Activity of telavancin against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) in vitro and in an in vivo mouse model of bacteraemia.

Author information

1
Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. shegde@theravance.com

Abstract

OBJECTIVES:

Infections caused by heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) are associated with high rates of vancomycin treatment failure. Telavancin is a bactericidal lipoglycopeptide active in vitro against Gram-positive pathogens including hVISA and vancomycin-intermediate S. aureus (VISA). This study characterizes the microbiological activity of telavancin against vancomycin-susceptible S. aureus (VSSA), hVISA and VISA strains.

METHODS:

Reference strains of VSSA, hVISA and VISA were assessed for potential telavancin heteroresistance by population analysis. In addition, the efficacies of telavancin (40 mg/kg subcutaneously every 12 h for 4 days) and vancomycin (110 mg/kg subcutaneously every 12 h for 8 days) were compared in a neutropenic murine model (immunocompromised female non-Swiss albino mice) of bacteraemia caused by hVISA strain Mu3. Blood and spleen bacterial titres were quantified from cohorts of mice euthanized pre-treatment and at 24 h intervals post-treatment for 8 days.

RESULTS:

Telavancin was active against all strains of S. aureus tested, with MIC values < or =0.5 mg/L. Population analyses revealed no evidence of subpopulations with reduced susceptibility to telavancin. In the murine bacteraemia model of hVISA infection, all animals were bacteraemic pre-treatment and mortality was 100% within 16-24 h post-infection in untreated animals. Treatment with telavancin was associated with lower spleen bacterial titres, lower rates of bacteraemia and lower overall mortality than treatment with vancomycin.

CONCLUSIONS:

These in vitro and pre-clinical in vivo studies demonstrate that telavancin has the potential to be efficacious in infections caused by hVISA.

PMID:
20139142
DOI:
10.1093/jac/dkq028
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center