title: Antibacterial activity of linezolid and vancomycin in an in vitro pharmacodynamic model of gram-positive catheter-related bacteraemia.
abstract: OBJECTIVE
  The aim of this study was to compare the activity of linezolid and vancomycin in an in vitro pharmacodynamic model to assess potential differences in activity against biofilm-embedded organisms.
  
  
  METHODS
  Single-lumen central venous catheters colonized with biofilm-embedded Staphylococcus aureus, Staphylococcus epidermidis or vancomycin-resistant Enterococcus faecium (VRE) were treated with simulated clinical dosing regimens of linezolid 600 mg every 12 h or vancomycin 1 g every 12 h in a one-compartment in vitro pharmacodynamic model. Quantitative cultures were sampled through the catheter and peripheral ports over 48 h to dynamically assess changes in the burden of catheter colonization and organism seeding, respectively. At 24 and 48 h catheters were removed, sonicated and cultured for adherent organisms.
  
  
  RESULTS
  Both linezolid and vancomycin suppressed bacterial growth on the catheter and release of S. aureus and S. epidermidis into the model compared with controls (P < 0.05), while linezolid also suppressed counts compared with control and vancomycin versus VRE. Neither agent completely eradicated bacterial colonization of the catheters. MICs for the isolates recovered from the model did not increase over time with linezolid or vancomycin exposure.
  
  
  CONCLUSIONS
  Lack of activity against biofilm-embedded organisms appeared to be the primary reason for microbiological failure of both drugs in the model.
authors.affiliation: The University of Houston College of Pharmacy, Houston, TX 77030, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Wiederhold
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Coyle
authors.forename: Issam I
authors.initials: II
authors.lastname: Raad
authors.forename: Randall A
authors.initials: RA
authors.lastname: Prince
authors.forename: Russell E
authors.initials: RE
authors.lastname: Lewis
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D015169:Colony Count, Microbial; D016984:Enterococcus faecium / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D023303:Oxazolidinones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid