title: Comparison of in vivo and in vitro pharmacodynamics of a humanized regimen of 600 milligrams of Ceftaroline Fosamil every 12 hours against Staphylococcus aureus at initial inocula of 106 and 108 CFU per milliliter.
abstract: In light of the in vivo/in vitro discordance among beta-lactams against Gram-negative pathogens, we compared the in vivo pharmacodynamics of humanized ceftaroline against 9 Staphylococcus aureus strains (MICs of 0.13 to 1 mg/liter) from published in vitro studies using standard and high inocula in the murine thigh infection model. Consistent with the in vitro findings, mean reductions of ≥1 log10 CFU were observed for ceftaroline against all strains using both standard and high inocula. These results suggest in vivo/in vitro concordance with no observed inoculum effect.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Wonhee
authors.initials: W
authors.lastname: So
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
authors.forename: Jared L
authors.initials: JL
authors.lastname: Crandon
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
authors.affiliation: Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015169:Colony Count, Microbial; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009503:Neutropenia / Q000276:immunology; D046915:Penicillin-Binding Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects*; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000097583:Ceftaroline