title: Evaluation of the extracellular and intracellular activities (human THP-1 macrophages) of telavancin versus vancomycin against methicillin-susceptible, methicillin-resistant, vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus.
abstract: OBJECTIVE
  To compare extracellular and intracellular activities of telavancin (versus vancomycin) against Staphylococcus aureus (MSSA, MRSA, VISA and VRSA).
  
  
  METHODS
  Determination of cfu changes (3-24 h) in culture medium and in macrophages at concentrations ranging from 0.01 to 1000x MIC.
  
  
  RESULTS
  Extracellularly, telavancin displayed a fast, concentration-dependent bactericidal activity against all strains. The concentration-effect relationship was bimodal for MSSA and MRSA [two successive sharp drops in bacterial counts (0.3-1x MIC and 100-1000x MIC) separated by a zone of low concentration dependency]. When compared at human total drug Cmax (vancomycin, 50 mg/L; telavancin, 90 mg/L) towards MSSA, MRSA and VISA, telavancin caused both a faster and more marked decrease of cfu, with the limit of detection (>5 log decrease) reached already at 6 versus 24 h for vancomycin. Intracellularly, the bactericidal activity of telavancin was less intense [-3 log (MSSA) to -1.5 log (VRSA) at Cmax and at 24 h]. A bimodal relationship with respect to concentration (at 24 h) was observed for both MSSA and MRSA. In contrast, vancomycin exhibited only marginal intracellular activity towards intraphagocytic MSSA, MRSA and VISA (max. -0.5 log decrease at 24 h and at Cmax).
  
  
  CONCLUSIONS
  Telavancin showed time- and concentration-dependent bactericidal activity against both extracellular and intracellular S. aureus with various resistance phenotypes. The data support the use of telavancin in infections where intracellular and extracellular S. aureus are present. Bimodality of dose responses (MSSA and MRSA) could indicate multiple mechanisms of action for telavancin.
authors.affiliation: Unité de Pharmacologie cellulaire et moléculaire, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Maritza
authors.initials: M
authors.lastname: Barcia-Macay
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemaire
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.forename: Paul M
authors.initials: PM
authors.lastname: Tulkens
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077427:Lipoglycopeptides; D008264:Macrophages / Q000382:microbiology*; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D013211:Staphylococcus aureus / Q000187:drug effects*; D013997:Time Factors; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; D014640:Vancomycin; C487637:telavancin