Related Experiment Video
Updated: Jun 26, 2026
In Vivo Mouse Model of Spinal Implant Infection
Published on: June 23, 2020
Efficacy of telavancin against glycopeptide-intermediate Staphylococcus aureus in the neutropenic mouse bacteraemia
Sharath S Hegde1, Stacey Difuntorum, Robert Skinner
1Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. shegde@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 10(7) 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.
Insights
Telavancin demonstrated superior efficacy over vancomycin in clearing infections caused by glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous vancomycin-intermediate S. aureus (hVISA) in a mouse model. These findings support further investigation of telavancin for treating GISA and hVISA bacteraemia.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Emergence of vancomycin-intermediate Staphylococcus aureus (VISA) strains, including glycopeptide-intermediate S. aureus (GISA) and heterogeneous VISA (hVISA), poses a significant therapeutic challenge.
- Neutropenic murine models are crucial for evaluating antimicrobial efficacy against serious bacterial infections.
Purpose of the Study:
- To compare the in vivo efficacy of telavancin and vancomycin against GISA and hVISA strains.
- To assess the effectiveness of these antibiotics in a neutropenic murine bacteraemia model.
Main Methods:
- Immunocompromised mice were inoculated with GISA (HIP-5836, Mu50) or hVISA (Mu3) strains.
- Mice received subcutaneous doses of telavancin (40 mg/kg) or vancomycin (110 mg/kg) at 4 and 16 hours post-inoculation.
- Blood and spleen bacterial titres were quantified at multiple time points.
Main Results:
- Telavancin exhibited significantly greater potency than vancomycin against all tested GISA and hVISA strains.
- Telavancin achieved sustained reductions in bacterial titres in blood and spleen.
- Vancomycin showed only transient or no significant reduction in bacterial counts for most strains.
Conclusions:
- Telavancin demonstrated superior efficacy in clearing GISA and hVISA infections in a neutropenic mouse bacteraemia model.
- The results suggest telavancin is a promising therapeutic option for GISA and hVISA bacteraemia.
- Further clinical evaluation of telavancin for these resistant infections is warranted.
