title: Pharmacodynamic activity of ceftobiprole compared with vancomycin versus methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) using an in vitro model.
abstract: BACKGROUND
  This study compared the pharmacodynamics of ceftobiprole and vancomycin against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA) using an in vitro model.
  
  
  METHODS
  Two methicillin-susceptible S. aureus (MSSA), two community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 x 10(6) cfu/mL and ceftobiprole dosed every 8 h (at 0, 8 and 16 h) to simulate the fC(max) and t(1/2) obtained after 500 mg intravenous (iv) every 8 h dosing (fC(max,) 30 mg/L; t(1/2,) 3.5 h). Vancomycin was dosed every 12 h (at 0 and 12 h) to simulate fC(max) and t(1/2) obtained after 1 g iv every 12 h dosing (fC(max), 20 mg/L; t(1/2), 8 h). Samples were collected over 24 h to assess viable growth.
  
  
  RESULTS
  Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin fAUC(24)/MIC of 340 (vancomycin MIC, 1 mg/L for MSSA and MRSA) resulted in a 1.8-2.6 log(10) reduction in colony count at 24 h. Vancomycin fAUC(24)/MIC of 85-170 (vancomycin MIC, 2-4 mg/L for VISA) resulted in a 0.4-0.7 log(10) reduction at 24 h. Vancomycin fAUC(24)/MIC of 5.3 (vancomycin MIC, 64 mg/L for VRSA) resulted in a limited effect.
  
  
  CONCLUSIONS
  Ceftobiprole T > MIC of > or =100% (ceftobiprole MICs, < or =2 mg/L) was bactericidal (> or =3 log(10) killing) against MSSA, CA-MRSA, HA-MRSA, VISA and VRSA at 16 and 24 h. Vancomycin was bacteriostatic against MSSA, MRSA and VISA, while demonstrating no activity against VRSA.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. ggzhanel@pcs.mb.ca
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Dylan
authors.initials: D
authors.lastname: Voth
authors.forename: Kim
authors.initials: K
authors.lastname: Nichol
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Noreddin
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D017714:Community-Acquired Infections / Q000382:microbiology; D003428:Cross Infection / Q000382:microbiology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C443755:ceftobiprole; D014640:Vancomycin