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JAC Advance Access originally published online on January 20, 2009
Journal of Antimicrobial Chemotherapy 2009 63(4):763-766; doi:10.1093/jac/dkp001
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Efficacy of telavancin against glycopeptide-intermediate Staphylococcus aureus in the neutropenic mouse bacteraemia model

Sharath S. Hegde*, Stacey Difuntorum, Robert Skinner, Justin Trumbull and Kevin M. Krause

Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA

Received 10 November 2008; returned 10 December 2008; revised 22 December 2008; accepted 29 December 2008

* Corresponding author. Tel: +1-650-808-6432; Fax: +1-650-808-6441; E-mail: shegde{at}theravance.com

Objectives: The aim of the study was to compare the efficacies of telavancin and vancomycin against glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous vancomycin-intermediate S. aureus (hVISA) in a neutropenic murine bacteraemia model.

Methods: Immunocompromised mice (female non-Swiss albino, 18–30 g) were inoculated intraperitoneally with 107 cfu/mL of GISA (strain HIP-5836 or Mu50) or hVISA (strain Mu3). Infected mice received a subcutaneous dose of telavancin (40 mg/kg) or vancomycin (110 mg/kg) at 4 and 16 h post-inoculation. Control animals received a subcutaneous dose of vehicle at 4 h post-inoculation only. Blood and spleen bacterial titres were quantified in drug-treated mice at 16, 28 and 52 h post-inoculation.

Results: Telavancin was 8-fold more potent than vancomycin against HIP-5836 (MIC 1 versus 8 mg/L), 16-fold more potent against Mu50 (MIC 0.5 versus 8 mg/L) and 8-fold more potent against Mu3 (MIC 0.25 versus 2 mg/L). Telavancin produced significant (P < 0.05) and sustained reductions in blood and spleen titres from pre-treatment levels in mice infected with HIP-5836, Mu50 or Mu3. Vancomycin lowered blood and spleen HIP-5836 counts transiently, but did not lower blood or spleen Mu50 or Mu3 counts significantly at any timepoint. Reductions in blood and spleen HIP-5836 and Mu3 titres and in spleen Mu50 titres at 52 h post-inoculation were significantly greater with telavancin than vancomycin (P < 0.05).

Conclusions: Telavancin was more efficacious than vancomycin in clearing infections caused by GISA strains HIP-5836 and Mu50 and hVISA strain Mu3 in a neutropenic mouse bacteraemia model. Further evaluation of telavancin for GISA and hVISA bacteraemia is warranted.

Keywords: vancomycin , GISA , heterogeneous VISA , hVISA


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