title: Effect of human plasma on the antimicrobial activity of iclaprim in vitro.
abstract: OBJECTIVE
  Iclaprim is a novel diaminopyrimidine for which a human plasma binding level of approximately 93% has been reported. The purpose of this study was to evaluate the effect of human plasma on the in vitro activity of iclaprim and to compare it with that of fusidic acid, teicoplanin and vancomycin, antibiotics with protein binding to human plasma of 97%, >90% and 55%, respectively.
  
  
  METHODS
  MICs were determined using 40 methicillin-susceptible Staphylococcus aureus (MSSA) and 38 methicillin-resistant S. aureus (MRSA) isolates in Mueller-Hinton broth (MHB) alone or in the presence of 50% human plasma.
  
  
  RESULTS
  MICs of iclaprim were not affected by the addition of human plasma. MIC ranges (MIC(90)) for iclaprim against MSSA and MRSA were < or =0.016-0.06 mg/L (MIC(90) 0.06 mg/L) and < or =0.016-0.5 mg/L (MIC(90) 0.06 mg/L), respectively, in MHB and < or =0.016-0.125 mg/L (MIC(90) 0.06 mg/L) and < or =0.016-0.25 mg/L (MIC(90) 0.125 mg/L), respectively, in the presence of human plasma. As expected, the antimicrobial activity of fusidic acid was greatly affected by the presence of human plasma (MIC elevations of 4- to >128-fold), whereas MICs of vancomycin remained unchanged. By contrast, despite the high protein binding, MICs of teicoplanin were only marginally affected by the presence of plasma with an MIC elevation of maximum 8-fold for two strains.
  
  
  CONCLUSIONS
  This study demonstrates that human plasma does not affect the MIC of iclaprim in vitro.
authors.affiliation: Arpida AG, Duggingerstrasse 23, 4153 Reinach, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Laue
authors.forename: T
authors.initials: T
authors.lastname: Valensise
authors.forename: A
authors.initials: A
authors.lastname: Seguin
authors.forename: S
authors.initials: S
authors.lastname: Hawser
authors.forename: S
authors.initials: S
authors.lastname: Lociuro
authors.forename: K
authors.initials: K
authors.lastname: Islam
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008712:Methicillin / Q000378:metabolism / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010949:Plasma / Q000378:metabolism*; D011485:Protein Binding; D011743:Pyrimidines / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D011743:Pyrimidines; C486448:iclaprim; D008712:Methicillin