Efficacy of telavancin against glycopeptide-intermediate Staphylococcus aureus in the neutropenic mouse bacteraemia model.
OBJECTIVE
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.
Hegde
Sharath S
SS
Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. shegde@theravance.com
Difuntorum
Stacey
S
Skinner
Robert
R
Trumbull
Justin
J
Krause
Kevin M
KM
D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D000077427:Lipoglycopeptides; D051379:Mice; D013154:Spleen / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin