title: Ceftaroline pharmacodynamic activity versus community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus using an in vitro model.
abstract: BACKGROUND
  This study assessed the pharmacodynamics of ceftaroline against methicillin-resistant Staphylococcus aureus (MRSA), heteroresistant (h) vancomycin-intermediate S. aureus (hVISA), VISA and vancomycin-resistant S. aureus (VRSA) using an in vitro model.
  
  
  METHODS
  Two methicillin-susceptible S. aureus (MSSA), one community-associated (CA)-MRSA, one healthcare-associated (HA)-MRSA, one hVISA, three VISA and two VRSA were studied. The pharmacodynamic model was inoculated with a concentration of 1 × 10⁶ cfu/mL and ceftaroline dosed every 12 h (at 0 and 12 h) to simulate the ƒC(max) and t(½) obtained after administering 600 mg intravenously every 12 h (ƒC(max), 16 mg/L; t(½), 2.6 h). Samples were collected over 24 h to assess viable growth and changes in ceftaroline MIC over time.
  
  
  RESULTS
  Ceftaroline ƒT(> MIC) of ≥ 92% (ceftaroline MICs, ≤ 1 mg/L) was bactericidal (≥ 3 log₁₀ killing) against MSSA, CA-MRSA, HA-MRSA, hVISA, VISA and VRSA at 12 and 24 h. No bacterial regrowth occurred over the study period and no change in ceftaroline MIC was observed.
  
  
  CONCLUSIONS
  Ceftaroline ƒT(> MIC) of ≥ 92% (ceftaroline MICs, ≤ 1 mg/L) was bactericidal (≥ 3 log₁₀ killing) against MSSA, CA-MRSA, HA-MRSA, hVISA, VISA and VRSA at 12 and 24 h.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. ggzhanel@pcs.mb.ca
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.forename: Emma
authors.initials: E
authors.lastname: Rossnagel
authors.forename: Kim
authors.initials: K
authors.lastname: Nichol
authors.forename: Lauren
authors.initials: L
authors.lastname: Cox
authors.forename: James A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: Sheryl
authors.initials: S
authors.lastname: Zelenitsky
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*; D017714:Community-Acquired Infections / Q000382:microbiology; D003428:Cross Infection / Q000382:microbiology; D006801:Humans; D066298:In Vitro Techniques; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013203:Staphylococcal Infections / Q000382:microbiology; D020713:Vancomycin Resistance; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097583:Ceftaroline